Wednesday, 14 August 2013

Prof Ziad A Memish: principal author of MERS-CoV data

Since the human cases of MERS-CoV started in 2012, the majority of publications describing signs and symptoms of disease, incubation periods, sites and routes of transmission clusters of infections have come from the Kingdom of Saudi Arabia, and most of those have involved co-authorship, usually as senior author, by Prof Memish. He also commented on the initial ProMED posting from Prof Ali Mohamed Zaki, which announced the MERS-CoV to the world. I wrote something about that back in May.

According to a WHO biography, Prof Memish is a senior infectious diseases consultant at King Fahad Medical City, Professor at Alfaisal University and King Saud University, President of the Saudi Association of Public Health, Adjunct Professor at Emory University. He is also the KSA Ministry of Health's Assistant Deputy Minister of Health for Preventative Medicine in the Kingdom of Saudi Arabia (KSA).


I've briefly compiled some (its not exhaustive) of Prof Memish's MERS-CoV-related literature,  looking at the points he has found interesting and/or lacking in data and  requiring more research. As someone at the current hotzone, these should be points worthy of addressing. I have ordered the papers in time - starting each with the number of known MERS-CoV cases listed by the paper:

  1. 3 Cases. In the article in the Saudi Medical Journal, Oct 2012, AlBarrak and colleagues noted:
    • The need for a validated serological test from international colleagues; 
    • 1/3 cases had farm animal exposure, but all cases had been exposed to dust storms through the summer, possibly aerosolized virus also
    • Investigations of potential animal reservoirs are in progress
  2. 9 Cases. In an article in the International Journal of Infectious Diseases, Dec 2012, Pollack and colleagues noted:
    • 5/9 cases had a history of prior animal exposure
    • They asked what the animals were and whether there had been any animal, including bat, studies?
  3. 9 Cases. In an article in Clinical Microbiology and Infection, Feb 2013, Gautret and colleagues noted:
    • Their study was not based on case selection using symptoms, but was a (first?) prospective screening study without regard for symptoms.
    • MERS-CoV was absent from departing or returning French Hajj pilgrims using a slightly adapted (different cycler, same primers) RT-PCR assay based on that of Corman et al.
    • 2012 French Hajj pilgrims had a lower flu vaccination rate than did a 2009 cohort
    • Limited data to support human-to-human transmission, suggesting zoonotic transmission is likely
  4. 15 cases. In an article in the Lancet Infectious Diseases, May 2013, McCloskey and colleagues noted:
    • The importance of rapid genetic sequencing as was shown during the SARS-CoV outbreak
    • Knowledge gaps include those pertaining to the source, mode of transmission, epidemiology  geographic distribution, predisposing factors for infection and disease, incubation period, immunopathogenesis, range of clinical manifestations and epidemic potential
    • Focus on the Middle East may be missing international MERS-CoV cases
    • Available molecular tests are experimental and their sensitivity and specificity require definition
    • Serological test are urgently needed for epidemiology and investigations of global distribution 
  5. 90 cases. In the Lancet Infectious Diseases, July 2013, Assiri and colleagues describe the largest case study so far noting:
    • MERS-CoV cases present with a wide range of clinical manifestations, with greatest impact in those with underlying comorbidities
    • Knowledge gaps (43 key gaps and priorities listed) include those pertaining to epidemiology, community prevalence, transmission, clinical course, diagnostics, patient management and infection control
  6. ? Cases. In the Eastern Mediterranean Health Journal, July 2013, Alwan and colleagues noted:
    • Priority to monitor for sustained human-to-human transmission
    • The global public health community must attempt to understand the public health risks posed by MERS-CoV
    • Knowledge gaps include those pertaining to source, how it emerged in humans, how widespread it is
    • WHO and the global community have benefited from willingness of countries in the region to share viruses and information immediately, allowing rapid development of diagnostic tests
  7. ? Cases. In the Eastern Mediterranean Health Journal, July 2013, Joseph and colleagues noted:
    • Knowledge gaps include those pertaining to spectrum of disease, changes in MERS incidence, case definition, source of infection.
    • There are global high expectations that everything is being done to detect and control an emerging disease threat; global preparation is needed due to uncertainties
    • Need to train laboratory staff for MERS-CoV testing, identify where capacity building is required and liase with animal research group to strengthen collaborative studies
  8. 90 cases. In the International Journal of Infectious Diseases, Aug 2013, Omrani and colleagues noted:
    • Nosocomial transmission may be occurring via undetected or asymptomatic healthcare workers
    • Knowledge gaps include those pertaining to source, intermediate host, pathogenesis, infectivity and risk factors
    • Diagnostic assays need optimizing
    • Therapeutic options need to be identified
  9. 94 cases. In the New England Journal of Medicine, Aug 2013, Memish and colleagues noted: 
    • Health care workers should be reminded of infection prevention and control measures
    • The KSA routinely screens all close contacts of MERS-CoV patients and this screening has identified 7 HCWs positive for MERS-CoV
    • How great a risk is posed to healthcare workers by MERS-CoV patient body fluids, excreta, bodily fluids, samples and surfaces contaminated by such
So, there is a consistent thread among these expert publications highlighting a need to find the animal host and requests for improved diagnostic tests, although I'm not sure what is wrong with the WHO-recommended assays. 

There is a similar need for antibody-detection (serological) tests. I believe these already exist, but are lacking in validation (proof they are as good at detecting negatives as positives, and not picking up too many false negatives or false positives). This will need a suitably large panel of known positive sera, best obtained from the most numerous source of cases, the KSA. Hopefully that is being assembled now, even if it requires contacting former patients, symptomatic or asymptomatic, to retrospectively ask for a blood sample. This is a one-off validation that would be invaluable to the world since there are multiple sources of MERS-CoV or virus proteins to make the assay, but sources of known positive sera are limited. 

As noted by Prof Memish, an antibody test would allow each country to see if MERS-CoV was was/had been active there and could be used to determine what level of mild or asymptomatic illness there is, if any, worldwide.

What Prof Memish and his co-authors and the world's scientist want to know seems to have been largely made clear back in 2012 when MERS emerged. What's unclear is what is being done to address the list (Ref 7 has a good example) and who is doing what?