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US CDC testing retrospectively for MERS in Jordan.

I'm little slow on this day old story. Jordan was the site of the first MERS-CoV cases, confirmed retrospectively by NAMRU-3 (see MERS page; Cluster #1). 

The US CDC has been sent 124 samples by the Jordan Ministry of Health from around that time to help further investigate the source of the (as far as we know) first outbreak. 

The 2 cases that had been confirmed were healthcare workers, including an intensive care unit nurse. This strongly suggests at least 1 patient with the unexplained pneumonia occurring in Jordan around April 2012, was a source of the MERS-CoV.
Raises the question of what Hajj 2012 serum samples would reveal?

Poultry workers had no prior exposure to H7N9 [UPDATED]

Bai and colleagues report in NEJM that 1,544 samples collected from young adult poultry workers between Jan-Nov 2012 in 4 key provinces/municipalities of China (municipality of Shanghai, Zhejiang province, Jiangsu province and Anhui province) were tested using a haemagglutinin-inhibition (HAI) assay and a microneutralization (MN) assay. 

The HAI assay found some weak reactivity (antibody was positive when diluted as far as 1:40), but no neutralizing antibodies were found by MN test. 

This is chapter 1 of a story that next needs to include more contemporary testing. 

The first part reveals no assay-specific antibodies present in these close contacts of poultry, prior to late 2012; before the H7N9 outbreak.

Nothing unusual about MTAs-are commenters just confused?

Material transfer agreements are more the norm than the exception among scientist used to local an d international collaborations whether working with exotic new viruses - or endemic seasonal viruses from the recent or distant past. 

An article in Science's ScienceInsider goes into more detail about the recent fracas. Perhaps some just don't understand the difference between MTAs, IP, business and public health needs?

It's worth noting that even if I wanted a sample of a common cold virus stored more than 50 years ago and now housed and maintained in one of the world's leading biological banks of such samples, I would have to sign an MTA that imposes restrictions on its downstream use. You can read the whole thing here...one excerpt....


ATCC Material and Progeny: ATCC Material and Progeny may only be used by Purchasers Investigator for research purposes and only in Investigators laboratory.

5 new MERS-CoV cases come from nowhere.

The Saudi Ministry of Health effusive detail below..


Within the framework of the epidemiological surveillance of the novel Coronavirus (MERS-CoV), the Ministry of Health (MOH) has announced that five novel Coronavirus cases have been recorded among citizens in the Eastern Region, ranging in age from 73 to 85 years, but they have all chronic diseases.
That's not an excerpt. That's all of it. Even Coulson wouldn't be that reserved.

H7N9 in Beijing.

Busy night. According to crofsblogs and Avian Flu Diary, Beijing has reported a new case of H7N9 in a 6M, confirmed 28.05.13. This makes 133 cases and 37 deaths-3 in Beijing when including an asymptomatic lab confirmation.
This case comes after Beijing rolled H7N9 into its normal influenza virus laboratory testing system and one of China's leading respiratory virus researchers noted the need to remain vigilant about H7N9.

H7N9: airborne transmission not at pandemic levels - infects upper & lower airways, lymph nodes and brain in ferrets.

In a collaborative effort published last week in Science, researchers from China, Canada and the US infected ferrets with a human H7N9 isolate (A/Shanghai/2/2013; "SH2"). The aim was to understand infection, transmission and pathogenicity due to the virus in the main mammalian model for such studies.

Ferrets showed upper respiratory tract disease, similar to that due to influenza A(H1N1)pdm 2009 virus infection, with shedding beginning the day after nasal inoculation - preceding any signs of disease. Obvious ramifications for stealthy spread of virus in this prodromal phase

Infected ferrets housed in the same cage as a non-infected ferret (introduced 24-hours after the the infection of the first occupants) easily transmitted SH2 to the newcomer who showed signs of illness within 36-hours; the same time at which lung inflammation and virus replication in nasal, tracheal, bronchiolar, lymph node and brain tissues was occurring. All these ferrets produced a diagnostic rise in antibodies by 14 days (They seroconverted).

An uninfected ferret in a downwind cage, separated by 10cm, acquired and shed SH2 at 36-hours after exposure (1 animal in 3 experiments). This ferret and one other seroconverted at 14 days post-exposure.

Airborne transmission was therefore possible in two-thirds of exposures in these experiments. H1N1pdm 2009 infected ferrets all shed virus regardless of route of infection confirming practically that H7N9 has some way to go to spread on a par with a known pandemic influenza virus.

Pigs also supported H7N9 infection showing signs and symptoms of disease 0.5 days after virus load was measurable. Direct contact H7N9 transmission was possible with an antibody rise occurring in 25% (1 of 4) of pigs but no virus shedding. No airborne transmission was detectable in the pigs. H1N1pdm 2009 virus was spread efficiently by direct and airborne routes in pigs.

Perhaps pigs are not the universal intermediary mixing vessel they are made out to be - being more susceptible to humanised influenza viruses than those closer to their avian hosts?

EV-A71 in cases of Acute Flaccid Paralysis (AFP), Australia.

ProMED describes a report from researchers at the Australian National Enterovirus Reference Laboratory on 5 cases of AFP positive for EV-A71 between Jan-May 2013. The viruses, found in stool samples from ill children, were identified as belonging to the more virulent genogroup, C4a, by VP1 sequencing.

Members of genogroup C4 were described by van der Sanden and colleagues as being restricted to epidemics in the Asian Pacific region.

Questions about MERS, MTAs and mistakes.

Edited by Dr. Katherine E. Arden

This is a story that stretches back to June 2012-nearly 12 months ago. That's when virologist Prof Ali Mohamed Zaki reportedly notified (or not, depending on the article) the Saudi Arabian Ministry of Health about a fatal case of severe acute respiratory infection in a 60-year old man for which the standard laboratory tests yielded no answers. He sent a sample to researchers at the Erasmus Medical Center (EMC) and followed that up with more testing. He and the Dutch researchers found a new coronavirus (CoV). What seems to be missing from this process was any formal release of that sample by the Saudi Arabian Ministry of Health (MOH). Prof Zaki's ethical position could be seen as murky at best.

On September 20th, an eMail Prof Zaki sent to ProMED was published notifying the world of his process (including how he detected the virus using PCR and grew the virus in culture-processes he conducted while working in Saudi Arabia) and his findings.
ProMED was subsequently dressed down by Deputy Minister for Saudi Arabian Public Health, Prof Ziad Memish for publishing the eMail about which the Ministry was unaware. Prof Zaki signed off his eMail from the Dr Fakeeh hospital Jeddah Saudi Arabia, a private hospital.

Prof Zaki's eMail served as a trigger for the testing of another ill male from Qatar who had been airlifted to the UK September 12th - that test yielded the second case of the novel coronavirus.

If Prof Zaki did not follow protocol and sent a specimen without the knowledge or permission of the Kingdom it is interesting, in light of the expected harsh consequences, to speculate on his reasons for doing so. Did Prof Zaki have the supervisory and ethical approval to send a clinical sample out of the country? Did the EMC challenge him on this before accepting the sample(s)? Had Zaki taken the approved steps (if he did not, that is) to notify his superiors and request permission to send a specimen for further characterisation, would he have received timely permission? Would he ever have received permission?

As a result of this situation, an article was published this week that, although lacking in clarity due to machine translation issues, vilifies Prof Zaki for his actions.WHO spokesperson Gregory Hartl was quoted during September 2012 as saying that the coronavirus "is now an international issue"; a comment that raises some questions in light of this latest article about Prof Zaki's actions. Some have expressed frustrationin recent days about the slow provision of information on new MERS-CoV cases. Would the new coronavirus have been made into an international issue if not for the actions of Prof Zaki? Is the Kingdom capable of characterizing a novel CoV? If the Kingdom did proceed with announcing the MERS-CoV and inviting international experts to advise, would it have done so in time to precede one of the most successful hajj gatherings ever? Nearly 4 million pilgrims attended that gathering in 2012. A real concern exists that cases of this unknown virus could disseminate globally because of just such a gathering. That did not happen but at the time no-one could be sure it wouldn't - the risk was evident and remains so for the coming hajj.

Also this week another cause for argument arose when National Microbiology Laboratory researchers in Canada stated that they were not allowed to pass on samples of the MERS-CoV to other laboratories (40 labs have received the virus from the Erasmus researchers to date). This restriction was stipulated in the Material Transfer Agreement (MTA) that accompanied the sample from the Dutch researchers at Erasmus Medical Center (who characterized HCoV-EMC, now known as the MERS-CoV). The comment that China "gave away" H7N9 samples has been used as an example of a better way to conduct collaborative research on emerging pathogens.

MTAs are a pain in the neck. They slow things down. They are not necessarily crafted by the researchers themselves but by the legal advisory team and administrators to protect new knowledge and discoveries. They can also manage and record where and to whom a putative pathogen is sent and what is done with it by the recipient. Is that a bad thing? MTAs are not uncommon in science. They protect many things. Yes, they can protect intellectual property-with the potential to make some money. Good luck with that - there are as many scientists who have found riches in this endeavor as there are Tony Starks and Bruce Waynes.In this case the MTA, among other things, reportedly limits the distribution of what iscurrently a virus with a case fatality rate of 50%. That sort of virus needs to be worked with by experts using expert facilities with suitable restrictions and pre-existing ethical, genetic manipulation and biocontainment standards in place. We observed the uproar among scientists recently when a recombinant influenza pathogen that had the (unproven) potential to be as lethal was created in secure laboratory environment.

Why has no such uproar accompanied the shipping of observably lethal viruses around the world in the absence of MTAs and tighter restrictions?

If other labs would like the virus, they can also apply to the lab that has gone to the effort to detect, characterize, isolate, grow, purify and store it - just as the NML did. The US CDC noted similar caveats on sharing MERS-CoV were put upon it by the UK laboratory that provided it with samples, presumably form the Qatar case.How long will the attacks on Prof Zaki continue? Hard to know. He is no longer working for the Kingdom. Is losing one's job enough punishment for his putative protocol breach?

It is encouraging to read that samples from various potential animals will be sent to researchers in the US who have the expertise to conduct the studies necessary to track down a possible host.

The first human case of MERS-CoV was in June 2012 - it's now May 26th 2013.

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