Monday, July 8, 2013

Recombinomics: WHO Forms MERS Emergency Committee

WHO Forms MERS Emergency Committee
Recombinomics Commentary 17:45
July 8, 2013
Fukuda: Okay, good question. So in terms of how often, just to remind you, the Emergency Committee is convened under the International Health Regulations so basically what that means is that the International Health Regulations envisioned the need for emergency committees to be stood up every once in a while. And so the International Health Regulations themselves were adopted in 2005 after SARS occurred but really came into force in 2007, that’s when they were actuallyimplemented.

The first time we used the emergency committee was during the 2009 H1N1 pandemic. That’s when we called it so this will be the second time that we will have convened an emergency committee. Anyway, it’s the second time.

So in terms of the control room we have something called – it’s basically an emergency operating centre – we call it the SHOC room – I think, Strategic Health…

Hartl: Operations Centre.

The above comments are from the transcript of the WHO June 5 press release on the emergency panel which is meeting tomorrow to assess the needs for additional actions regarding the MERS-CoV outbreak, which is largely limited to countries in the Middle East (the need for emergency committees was inspired by the 2003 SARS outbreak)..

The press release offered few clues on the timing of the meeting since the number of reported cases has been approximately 20 for each of the past three months.  However, the lack of information on mild or asymptomatic cases was cited and there have been a number of developments in this area in the past several weeks.  WHO also released new guidelines on case definitions (on July 3) which addressed issues associated with recent reports, which have raised questions about reporting of mild and asymptomatic cases, including possible gaming of the IHR reporting rules through the use of false negatives.

The reporting concerns began to increase in the spring when Kingdom of Saudi Arabia (KSA) officials noted that MERS-CoV cases where much like flu cases in that most cases survive without hospitalization or treatment and most of these mild cases were in Jeddah.  However, at the time there were no mild Jeddah cases reported.  The only reported case linked to Jeddah was the first confirmed case (60M) who lived in Bisha, but was treated and died in a hospital in Jeddah.  Moreover, the only reported Jeddah case since the comments in the spring was a child (2M), who recently also died.  Thus, to date there have been no mild cases reported from Jeddah, although milder cases have recently been reported in Taif (see map).

The comments on mild cases in Jeddah raised concerns that there cases were testing positive, but were not being reported because they were weak positives and a higher cut-off was being used to define a positive case, or samples were degrading between collection and confirmatory testing, so patients were not being confirmed because the second test was (falsely) negative.

Testing issues became more obvious due to recent developments.  Symptomatic Health care workers and cases in France were said to be negative, but the home quarantine or immediate hospital discharge suggested that these symptomatic contacts had recovered prior to sample collection, and the negative data was false. 

This possibility was increased by subsequent results from Italy.  Two confirmed contacts tested positive prior to hospitalization, but were discharged a few days later when they tested negative.  These two cases indicated the window of opportunity for detection of MERS-CoV in mild cases was small and samples collected several days after disease onset would be negative for mild infections.

Testing issues were also raised when contacts in Italy, including five health care workers produced weak positives.  Although the weak positives were not confirmed by a second lab, different PCR primers were used raising concerns that the use of tests with a lower sensitivity would produce false negatives for samples that produced weak positives with more sensitive tests.

In addition to the suspect negatives in France and Italy, results from serum antibody testing of ICU contacts from the 2012 outbreak in Jordan confirmed MERS-CoV in an asymptomatic and mild case (both recovered without treatment or hospitalization).  Moreover, positive results with one of the two antibody tests suggested additional mild or asymptomatic cases would be confirmed with a more optimized antibody test, indicating additional spread to ICU contacts (as well as additional mild and asymptomatic cases).

Moreover, KSA then reported PCR confirmation of MERS-CoV in mild and asymptomatic contacts, which WHO described as “weak positives”, which once again raised concerns that cut-off changes or improved sample handling led to confirmation of cases similar to the earlier Jeddah ‘mild” cases which were not reported.

The testing concerns have been addressed in the WHO case definition update, which classifies these cases as probable.  These mild or asymptomatic cases are important for determination of transmission chains and the conversion of “seemingly sporadic” cases into clusters  and the limited human to human transmission into sustained transmission.

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