Wednesday, February 04, 2015

WHO MERS Update & The Community Transmission Mystery

The figure is an epidemiologic curve showing the number of cases of Middle East respiratory syndrome (MERS) coronavirus infection reported by the World Health Organization, by month and year of illness onset, worldwide during 2012-2015. The majority (504) of the 956 MERS cases were reported to have occurred during March-May 2014.

CDC MMWR - Number of cases of MERS infections reported by the World Health Organization,* by month of illness onset — worldwide, 2012–2015

 

# 9669

 

It’s been nearly three years since the first known cases of MERS in the Middle East, where an outbreak at a Jordanian hospital infected at least 9 people (see Serological Testing Of 2012 Jordanian MERS Outbreak), killing two. At the time, and for about the next six months, the cause of that outbreak was a mystery.

 

In the summer of 2012 a letter posted in ProMed Mail (NOVEL CORONAVIRUS - SAUDI ARABIA: HUMAN ISOLATE) by Dr. Ali Mohamed Zaki - an Egyptian Virologist working In Saudi Arabia – announced the discovery of a new coronavirus in a Saudi Patient.

 

Retrospective testing later that year revealed the Jordanian cluster to have been caused by the MERS-CoV as well.


We saw a slow increase in cases in 2013, and an explosion of cases in the spring of 2014, with more than 500 cases in a three month period.  The majority of these cases were male, elderly, and many had co-morbidities. For many, the source of infection was fairly obvious. 

  • A few appear to have acquired the virus from a zoonotic source, primarily camels. 
  • Many were exposed in healthcare settings, including HCWs
  • Others were family members or close contacts of known cases

 

But for a lot of cases, the mode of exposure wasn’t at all obvious.  

 

No recent history of animal contact, or direct contact with a known case in a healthcare or community setting.  While still predominantly male, elderly, and many with co-morbidities, exactly how and where they contracted the virus was a mystery.


One of the tools epidemiologist’s use to figure these things out is a case-control study, where they compare laboratory-confirmed cases to a large number of controls, matched for age, sex, and by neighborhood. 

 

By examining their respective exposures against their outcomes, patterns of risk are often revealed.


In CDC: Risk Factors Involved With H7N9 Infection, we looked at a case-control study that was begun in China literally weeks after the first cases of H7N9 infection were identified, that  quickly nailed down live bird markets as the primary source of infection.

 

At roughly the same time (summer of 2013) the World Health Organization published a framework for just such a project on MERS (see case-control study protocol), and entreated the Saudi Ministry of Health to conduct, and publish, the study. 

 

While repeated promises have been made (see KSA Announces Start To Long-Awaited MERS Case Control Study), for whatever reason, we’ve yet to see the results.

 

Another epidemiological tool is broad based community seroprevalence studies, which would give us some idea of the incidence of infection across the population. But if this has been done, the results have not been published. 

 

And so 18 months later we continue to see WHO updates, like the one published yesterday, where the source of infection for many cases remains a mystery.  In this latest report, while three of nine cases had some (often fleeting) exposure to health care facilities, none was known to have had contact with a MERS case or camels.

 

First the WHO GAR report (bolding mine), then I’ll return with a bit more.

 

Middle East respiratory syndrome coronavirus (MERS-CoV) – Saudi Arabia

Disease outbreak news
3 February 2015

Between 14 and 22 January 2015, the IHR National Focal Point for the Kingdom of Saudi Arabia (SAU) notified WHO of 9 additional cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection, including 4 deaths. Cases are listed by date of reporting, with the most recent case listed first.

Details of the cases are as follows:
  • An 84-year-old female from Riyadh city developed symptoms on 19 January and was admitted to a private hospital on 20 January. The patient has comorbidities but no history of exposure to any known risk factors in the 14 days prior to the onset of symptoms. The patient was in ICU in critical condition. Since then, she recovered and was discharged on 27 January.
  • A 77-year-old male from Riyadh city developed symptoms on 18 January and was admitted to a private hospital on 21 January. The patient has comorbidities but no history of exposure to any known risk factors in the 14 days prior to the onset of symptoms. The patient was in ICU in critical condition. Since then, he recovered and was discharged on 28 January.
  • An 80-year-old male from Riyadh city developed symptoms on 26 December and was admitted to hospital on the same day. The patient had comorbidities. On 26 December, he was in an emergency room where two previously reported MERS-CoV cases had been treated, although the patient had no direct contact with either case. He had no history of exposure to other known risk factors in the 14 days prior to the onset of initial symptoms. The patient was in ICU and passed away on 23 January.
  • A 38-year-old male from Riyadh city developed symptoms on 14 January. The patient, who has comorbidities, was initially admitted to hospital on 1 January for a surgical procedure. On 7 January, during his admission, he went out on a day-release where he visited his family in Aldawadmi city. On 12 January, the patient underwent surgery in a hospital where a laboratory confirmed MERS-CoV case had also been treated, although there is no history of contact between the patient and the case. He has no history of exposure to other known risk factors in the 14 days prior to the onset of symptoms. Currently, the patient is in stable condition and remains in isolation.
  • A 76-year-old male from Riyadh city developed symptoms on 12 January. The patient, who had comorbidities, was initially admitted to hospital for an unrelated medical condition on 3 November. He received care in a hospital where a laboratory confirmed MERS-CoV case had also been treated. The patient had no history of exposure to other known risk factors in the 14 days prior to the onset of symptoms. He was in critical condition and passed away on 18 January.
  • A 67-year-old male from Riyadh city developed symptoms on 12 January and was admitted to hospital on 16 January. The patient has comorbidities. He frequently visited a health-care facility in Riyadh to treat his unrelated medical condition but has no history of contact with patients with respiratory symptoms. The facility is not associated with previous known MERS-CoV cases. There is no history of exposure to any known risk factors in the 14 days prior to the onset of symptoms. Currently, the patient is in stable condition and remains in an isolation ward.
  • A 62-year-old male from Riyadh city developed symptoms on 14 January and was admitted to hospital on 16 January. The patient has comorbidities. He has no history of exposure to any known risk factors in the 14 days prior to the onset of symptoms. Currently, the patient is in stable condition and remains in an isolation ward.
  • A 67-year-old male from Taif city developed symptoms on 5 January and was admitted to hospital on 9 January. The patient had comorbidities. He had no history of direct contact with camels or consumption of camel products but lived in an area with heavy presence of camels. The patient had no history of exposure to other known risk factors in the 14 days prior to the onset of symptoms. He was in critical condition and passed away on 21 January.
  • A 93-year-old male from Riyadh city developed symptoms on 11 January. The patient, who had comorbidities, was initially admitted to hospital for an acute injury on 28 December. At that time, the hospital was treating a laboratory confirmed MERS-CoV case. The patient had no history of exposure to other known risk factors in the 14 days prior to the onset of symptoms. The patient was in critical condition in ICU and passed away on 15 January.

Contact tracing of household contacts and healthcare contacts is ongoing for these cases.

The IHR National Focal Point for the Kingdom of Saudi Arabia also notified WHO of the death of 2 previously reported MERS-CoV cases. The cases were reported in previous DONs on 5 January (Case n. 2) and on 15 January (Case n. 3).

Globally, WHO has been notified of 965 laboratory-confirmed cases of infection with MERS-CoV, including at least 357 related deaths.

(Continue . .. )

 

We know the  MERS coronavirus can produce a wide spectrum of disease in humans.  Among diagnosed cases - roughly 50% are severe or life threatening while roughly 20% are described as being mild or even asymptomatic.

 

The question of `asymptomatic’  transmission of the virus has yet to be answered, although we’ve seen hints that it may be a factor (see Study: Possible Transmission From Asymptomatic MERS-CoV Case).


As with any infectious disease, there are probably more cases in the community than we know.  Surveillance isn’t perfect, and only those sick enough to be hospitalized (or picked up as a close contact of a hospitalized patient) are likely to be detected.  

 

Those with mild illness may well think they have nothing more than a cold, or the flu.


In November of 2013, we looked at a study published in The Lancet Infectious Diseases, that attempted to quantify the likely extent of transmission of the MERS virus in the Middle East. (Middle East respiratory syndrome coronavirus: quantification of the extent of the epidemic, surveillance biases, and transmissibility).

 

They calculated  that for every case identified, there are likely 5 to 10 that go undetected.

 

While only an estimate, this is in line with studies of other novel viruses that seek to estimate uncounted cases.  And if true, would provide a plausible answer as to how hundreds of people – without obvious exposures – continue to contract the virus in the community.

 

Or there could be another explanation entirely.  

 

But we won’t know that until the proper studies are completed and published.

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