Friday, November 15, 2013

Second Report Shows MERS Epidemic is Under Way

Probable infections by country and confirmed cases. Image from PLoS
The Center for Infectious Disease and Prevention (CIDRAP) reported on two studies concerning the MERS (Middle East Respiratory Syndrome) virus which have recently been released.

Both reviewed data on MERS infection rates and determined there are many unreported cases of the disease. The virus is not believed to have achieved sustained human-to-human transmission and outbreaks of the illness can be controlled without 'overly aggressive' measures.

The first study, conducted by the Imperial College London, the University of Edinburgh, and the Institut Pasteur in Paris and published in The Lancet Infectious Diseases, found that for every identified case, there were five to ten which were unreported. They estimated there were 940 human symptomatic cases by August 8, 2013 and noted that approximately 62% of 'clinically apparent' cases have gone undetected.

They determined that each infected persons transmitted the disease to one or two others after returning home, however the size of the clusters and rate of reproduction within those clusters decreased over time. They speculated this may be due to faster detection and response to cases.

Their report put the 'R value', or the reproductive rate of the disease, at between 0.8 and 1.3 when no infection control measures were implemented. A value of 1.0 is considered the level which the virus can be self sustaining.

Three data sources indicated that the R level ceiling could not be too much above the crucial 1.0 mark, most likely between 1.2 and 1.5. However, the researchers cautioned, "Our analysis demonstrates that the transmissibility of MERS-CoV in man is close to the critical threshold of R=1 required for self-sustaining transmission."

The scientists looked at infection rates in both animals and humans. By identifying mutations in genetic sequences which occur at a regular rate, they estimated between March 2012 and August 8, 2013, there were a staggering 17,940 infections in the human and animal population, according to CIDRAP.

The report concludes there is certainly an epidemic under way, they but could not determine if the virus is self sustaining in humans or if the epidemic is being sustained through an animal reservoir.

The second, more detailed study, conducted by PLoS Currents, also determined that spread of the virus could be stopped by 'appropriate infection control measures." The researchers felt R = < 1.0 but some estimates put the R level at > 1.0.

They looked at 144 confirmed and 17 probable cases occurring between September 2012 and October 2013 including 65 deaths. The researchers determined the median age was 50 and two thirds of the victims were male. Two thirds of the cases were considered 'severe' and three quarters had an underlying medical condition. Pre-existing health problems were more common among the fatal cases.

22 of the studied cases were considered 'index cases' which is the first infection within a cluster. 95 of the infected were considered 'secondary', that is they had contact with other confirmed cases. 29 of the cases were considered 'sporadic', meaning they had no known contact with previous ill patients or animals.

Index and sporadic case patients were more likely to 'have severe disease and were generally older, 59 years median compared with the 43 years in secondary cases.

The majority of the secondary cases were infected in health care settings, accounting for 60 of the 95 cases in that group. Thirteen cases were spread through household contact and one at work. Only seven of 49 infected persons had contact with animals in the previous ten days, five were exposed to camels and two to sheep. More detailed demographic data from the study can be found here.

Maria D. Van Kerkhove, PhD, who coauthored both reports, concurred that cases are being unreported due to surveillance policies which were designed to identify severe cases. The tendency to report only the most gravely ill probably has skewed the statistical mortality rate, which has been quoted at near 50%.

The study concludes that the reported cases, "probably represent the severe end of a wide clinical spectrum of disease...Thus the case-fatality ratio (CFR) is probably lower than it looks now, though a CFR higher than 10% cannot be ruled out."

"I think countries in the region have certainly stepped up surveillance activities in recent months, but we are still likely to miss the more mild or asymptomatic cases because current surveillance recommendations will not identify those," Van Kerkhove said.

She is not surprised at the recent discovery of MERS infected camels. Regarding whether spread of the virus is being sustained through human contact or if an animal source is continually seeding the epidemic through ongoing transmission to humans, Van Kerkhove thinks it is both.

"I think we're seeing a combination of the two. There is certainly human-to-human transmission occurring, but we also continue to see a number of isolated cases reported without any epidemiologic links to other cases, indicating that there is likely non–human-to-human exposure occurring."

The CIDRAP article also noted, per the World Health Organization:
  • "Initial MERS symptoms typically include fever, cough, chills, sore throat, and muscle and joint pain, followed by dyspnea (shortness of breath).
  • At least a third of patients had gastrointestinal symptoms such as vomiting and diarrhea.
  • Many patients have been treated unsuccessfully with high-dose corticosteroids, and the WHO recommends against such treatment, with few exceptions.
  • No antibiotic or antiviral agents have been effective in treating severe MERS cases.
  • Unpublished data shows that MERS-CoV is closely related to coronaviruses found in hedgehogs (and various studies show it is related to coronaviruses in bats).
  • Genetic analyses suggest that the virus emerged in mid-2011".

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