MERS misses Mumbai man

Hat tip to @makoto_au_japon

According to a DNA report (a Mumbai-based, English broadsheet daily owned by Diligent media Corp in case you were wondering), the 40-year man from Mumbai is not positive for the MERS-CoV. He is also negative for "swine flu" (pick one)...what he is positive for is unclear but he is recovering.

Just another insight into how often we don't know what causes an acute respiratory infection ...and this is the case worldwide, not just in India.

Oh for a Tricorder.

Read More

Health infrastructure at the site of the suspect MERS case in Mumbai, India

Hat tip to @makoto_au_japon for bringing this article to the fore

Facilities for patient isolation at the Kasturba hospital, Mumbai, where the 40M undergoing testing for (hopefully) a range of respiratory viruses including MERS-CoV, are less than ideal.

A report on The Times of India notes poor bed separation, concern for healthcare workers (HCWs) dealing with the case (whatever respiratory virus they have) and whether World Health Organisation minimum requirements of management of patients with airborne infections can be met. N95 particulate respirators are considered very important for protection of HCWs and caregivers.

If the case is MERS-CoV negative, this may be something of a wake-up call to the regional health authorities.

Read More

H5N1 did not transmit easily between humans in the wild...

Hat tip to @Laurie_Garrett and CIDRAP

Despite wearing next to no personal protective equipment (5% of 419 contacts used a mask, face shield, gown or gloves) and coming into contact with sick or dead poultry (12% of contacts), 85/87 household members and 332 "less close" contacts of 23 influenza A(H5N1) virus cases did not show any significant sign of antibodies to the virus, a study published in PLOS|ONE by Bai and colleagues noted.

Only 2 (0.4% of all contacts tested) were defined as infected by H5N1  during the study period of 2005-2008, on mainland China. 

The study used both haemagglutination test (antibodies in the patients sera bind horse red blood cells together giving a distinctive pattern) and micro-neutralization (presence of specific antibodies in a sample prevents a lab stock of virus from infecting a cell line-amount of virus can be determine by making dilutions of  the sample and comparing to a sample with no antibodies to the virus). When they had a single serum, the authors used:

• A neutralizing antibody cut-off titre of =40 children (<14-years of age)  with a haemagglutination titre =40.
• A neutralizing antibody cut-off titre =80 for those aged 15-59-years with a haemagglutination titre =40.

For acute and convalescent sera pairs positivity to H5N1 was defined as:

• A =4-fold rise in neutralizing antibody titre between acute and convalescent sera
• Convalescent sera needed a neutralizing titre of =40 for children and =80 for adults, or a haemagglutination titre =40

There were a few more positives below these cut-offs.

While genetically altered H5N1 can be made to spread among ferrets in the lab, it seems that some years ago in the wild, H5N1 had a ways to go before it could spread efficiently between humans. That's a good thing.

Read More

Suspected case of MERS-CoV in India...

A story at The Times of India describes a 40-year old male with fever and pneumonia who has been quarantined after returning to India from 35-days in the Kingdom of Saudi Arabia.

The patient is responding well to oseltamivir medication which does not support a MERS-CoV infection, rather an influenza infection. 40M has already tested negative for influenza A(H1N1) and MERS-CoV was suspected based on his travel history.

Testing at the National Institute of Virology in Pune, is ongoing.

FluTrackers has a thread on this story too.

Read More

Its probably not a MERS-CoV!

I commented on a news article from tweeted by @pandemic_News yesterday....

@pandemic_news Woah!! There is a known FELINE coronavirus...that is not at all #MERS-CoV. See pink filled circles at http://t.co/vUEyD2FoaO
� Ian M Mackay, PhD (@MackayIM) August 14, 2013

The article's headline had read MERS corona kills cat in the East. It seems to have been picked up some others overnight. 

I notice the headline has been changed today. [UPDATE 160813-the concept of a "feline reservoir has not been picked up by ProMED and a new version can be found at the Saudi Gazette.]

MERS-CoV is not the only CoV on the block of course. Have a look at the phylogenetic tree I posted a few days back - there are lots of CoVs and they infest a large number of different animals. The feline coronavirus (feline infectious peritonitis virus; FIPV) is an alphacoronavirus. It's well known. [UPDATE] It's probably the cause here. There is no evidence to support MERS-CoV in these animals. None.

I think headlines like this are akin to spam email - try and find a fact in there that has, or can be, verified from a trusted source, think about whether it makes sense (is this website likely to be the first one to report on MERS-CoV in cats?) or look for a reference in the text to an entirely different source (like a lab test result for example). That approach is not foolproof - but it's better than believing something so dramatically different from what we currently know, on first read.

Read More

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?

Read More