Middle East coronavirus infection control and personal protective equipment...

...are not at all part of the thinking judging by the imagery in this story on alRiyadh.

For a virus that kills 2 in 5 symptomatic people and for which animal hosts or intermediate hosts remain to be excluded or confirmed, there is an alarming and completely irresponsible level of safety being employed by those workers.

Thanks to FluTrackers for bringing it to my attention.

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Cute little hedgehogs get CoVs too?

Corman and colleagues from the University of Bonn Medical Centre (clearly not just for human medicine!) have found a proposed new species of coronavirus (CoV) they've assigned to the Genus Betacoronavirus clade C. The new virus is called erinaceus CoV (EriCoV). It inhabits the same clade  that houses the MERS-CoV, but it is not as closely related as are batCoVs and MERS-CoV.

The authors, writing in the Journal of Virology, thought that searching in an order of insectivorous animals, the Order Eulipotyphla, might yield results since most CoV-positive bats (Order Chiroptera) are insectivorous. 

Two of 146 (58.9% of 248 samples were tested  positive sample were targeted for genome sequencing using next generation (454) and conventional PCR sequencing technology, from European hedgehogs (Erinaceus europaeus). Virus was not isolated in cell culture using Vero, pipistrellus bat or shrew (same Order) cells making it less promiscuous in culture than MERS-CoV. Also, it probably uses a different receptor. No sign of disease could be discerned.

With GenBank recovering from being shuttered, it might be a while until the sequences are publicly available.

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A summary of Influenza A(H7N9) virus findings in birds and humans [UPDATED, AMENDED FIGURE]

An article from Bloomberg news highlights some interesting studies, how they present opposing conclusions and why we can expect to see more H7N9 activity, perhaps peaking at Chinese New Year.

Click on image to enlarge.
H7N9-positive birds and humans (see MOA report) in 
April 2013. 17x more humans were virus-positive 
than humans were PCR/symptom positive. Based on 
Li et al's April 24th New England Journal of Medicine 
article from a similar time period which uses observation 
for signs of disease among 1,251 followed contacts of 81 cases and
sentinel surveillance PCR data from 5,551 humans to
identify H7N9 cases).

The authors (Khan and Loo) remind us that earlier in the year, China's Ministry of Agriculture reported 46 positive poultry samples among 68,060 tested positive using viral culture, for H7N9 (0.07% or about 1:1,500). 

In a more detailed report from MOA from 30th May 2013, 88 of 899,758 [0.009%] duck, pigeon, chicken (722,380 or 80% of all the samples tested), wild bird, pig, geese, "other" animal or environmental samples were virus [197,389 of the samples tested this way] &/or antibody [702,369 of the samples] positive (chicken, duck and pigeons were the positives; 3 were positive for both). The report presented by Zhang Zhongqiu does not make clear how many swabs and bloods were tested per animal so I'll just talk about sample numbers. The report notes that there were no clinical cases reported from 44 million farming households and no positives from 51,876 samples of 746,212 samples (?chickens) sent to Hong Kong; monitored by the General Administration of Quality Supervision, Inspection and Quarantine, China) nor among the 120/samples being tested per day in Hong Kong. In 1,874 samples collected from Henan and Jiangxi provinces, none were positive. Transmission among chickens was possible but was not efficient among ducks.

• Lam and colleagues (previously reviewed) identified 8 avian H7N9 strains from 1,308 (0.6%) chickens (95% of samples), ducks, pigeon and geese samples collected from live bird markets (LBMs) in Rizhao, Shandong province (about 9 times more than the 1st MOA study above, if they can be compared directly). 
• Yang and colleagues (previously reviewed) found H7N9 antibodies in 25 (6%) of 396 humans poultry workers (none prior to 2013) but only 9 of 1,129 (0.8%) members of the general community showed some weak sign of past exposure (or cross-reaction with another influenza). No viral RNA was found in these poultry workers.
• Wang and colleagues, writing in the Journal of Infectious diseases,  recently traced the source of some cases in the Hangzhou region of Zhejiang, to LBMs. 95 samples from chickens (n=47 samples), ducks (n=9), quails (n=2), pigeons (n=3) and poultry handlers and 4 from water were inoculated into eggs and were tested by real-time RT-PCR, within the first 2-weeks of April 2013. H7N9 RNA was found in 41/85 (48%) of samples. 40% of the chicken samples, 89% of the duck samples and a third of the pigeon samples. No human or environmental samples were positive. The authors concluded that migratory birds would continue the spread of H7N9 viruses and that their findings highlight LBMs as the major source of infection an as such control measures are needed.
• Shi and colleagues reached a similar conclusion in April in the Chinese Science Bulletin. "Strong measures" were needed to control the spread of H7N9 in order to prevent more infections. This followed the testing of 970 samples of drinking water, soil, cloacal and tracheal swabs from LBM poultry in Shanghai and Anhui province using egg inoculation. All 20 (10 from chickens) of the H7N9 isolates came from LBMs in Shanghai, confirming high genetic homology across the H7N9 genome from human H7N9 cases.

Today's Bloomberg article quotes researchers' concerns that the cooler weather will drive the re-appearance of H7N9, since influenza usually reaches epidemic levels during cooler months. In other words they believe this particular strain of H7N9 (the one infecting humans) was never removed from the ecosystem.

Re-opening of the LBMs has been ongoing since June in Shanghai municipality and Zhejiang and Jiangsu provinces, albeit in a more regulated fashion. The cleansing of the markets after culling more than 560,000 poultry from LBMs as of May 2013 combined to precede the precipitous decline in what had been an alarming rate of new cases in those regions. Is testing of these markets an ongoing process?

With the markets refilling from farms located in rural regions with exposure to mobile wild bird populations that may (albeit infrequently) carry H7N9 (and many other influenza viruses including its components), the risk of fresh outbreaks among humans is also growing. 

It's a numbers game. 

Even 1 human case, like the one we saw infected this week could signal an even wider level of circulation of H7N9. Let's hope testing will make sure our number's not up this time around.

Editor's Note - the figure was altered 01.02.14 to correct an error in the proportions and to adjust down the number of contacts since not all had been followed.

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Middle East respiratory syndrome coronavirus: how tough is it?

Slide tweeted by @HZowawi captured from my talk on H7N9
and MERS-CoV presented at the Royal Children's Hospital,
Brisbane, Queensland, to the local Serology/Virology &
Molecular Special Interest Group of the Australian Society
of Micorbiology. 15th October, 2013.

This publication is nearly a month old so apologies if you know of it already.

For the rest of you, Doremalen, Bushmaker and Munster recently wrote in Eurosurveillance about the results of their experiments to discover how resilient MERS-CoV is on surfaces at different humidities and temperatures and how it survives in an aerosol. They also used MERS-CoV (the EMC/2012 strain) to influenza A (H1N1)pdm09 (Mexico/4108/2009 strain) virus for comparison.

Some key findings below (you can read the entire article yourself because this excellent journal has open access):

• Plastic and steel surfaces behaved similarly for these viral survival studies
• MERS-CoV was still infectious after 48-hours at 20�C in 40% relative humidity (RH; low humidity similar to indoors). 
• MERS-CoV remained viable for 8-hours at high temperature (30�C)/high humidity (80% RH) and 24-hours at high temperature/low humidity (30% RH)
• (H1N1)pdm09 was inactivated after 4-hours at any of those conditions
• Viruses were aerosolised and the amount of viral RNA and viral infectivity compared at 20�C/40%RH or 20�C/70%RH, after the aerosol was impinged into tissue culture medium.
• MERS-CoV viability dropped 7% at 40%RH and 89% at 70%RH - both at 20�C. Viral genome copies did not drop significantly.
• (H1N1)pdm09 dropped 95% and 62% respectively.
• SARS-CoV reportedly survives for 5-days at 22-25�C and 40-50%RH

The authors go on to conclude that MERS-CoV remains viable in the air and on surfaces for longer than a pandemic influenza virus. When you consider that a pandemic results largely from efficient transmission, of which virus stability is a component, this is a significant study.

These are pure preparations of virus under experimental conditions so it's fair to say that things would be different "in the wild". Rougher environmental conditions may accelerate viral decay although, if larger droplets were expectorated during coughing fits, extra material may act to prolong the survival of virus.

Transmission through fomites (e.g. door handles, glass screen phones, other hard surfaces, cups, utensils, clothing) is a possible route that now has some data to support it-although the current high temperatures (30s-40�C) in the Kingdom of Saudi Arabia suggest survival on surfaces, away from air conditioning, won't be for long.

What would be nice to know next, is whether mild and moderate cases of MERS are also capable of producing aerosolised virus. And what about asymptomatic cases? What about the mysterious animal sources? Could infected animal excreta further prolong viral survival? So many questions.

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Influenza A(H7N9) virus case appears in Zhejiang province....

Look I know hypotheses are there to be disproved  but did this one have to be shot down in flames 60-minutes after I said at a talk today, "...perhaps the very quick and large scale bird cullings and the live bird market closures actually eliminated the particular H7N9 that was spreading through humans in South East China earlier in the year. Perhaps even  reaching far enough back to require a whole new random chance mixture of the different H7s and N9s and other genome segments to occur before that virus would ever be seen again."

Brrraaappppp!!!!!

Today we see the first new H7N9 case since early August (which was an onset of July 28th).

A 35-year old male from Shaoxing County, hospitalised on October 8th, tested positive by PCR. He is in serious condition.

Peak daily temperatures are not high in this part of the world currently - below 25'C for the week.

It looks like H7N9 might be well entrenched after all. Where there are severe cases, there may well be less severe ones. 

A scientific article that I reviewed back in August, written by Yang and colleagues, showed that some poultry workers had been exposed to H7N9. These were relatively younger and healthier people than the PCR-positive ill H7N9 cases.

We're in for some interesting times ahead with H7N9; it's not done with us yet.

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The Hajj begins

The Kingdom of Saudi Arabia showing the major sites of MERS-CoV
infections and the site of Mecca.

Al Riyadh reports that on Saturday and Sunday 13th the 1,379,000 international pilgrims (94% arriving by air) moved into Mina Valley from the holy city of Mecca (Makkah) located in the Mecca province, the most populated province of the Kingdom of Saudi Arabia (over 5.8 million people). The number includes 752,424 males (55%).

The Hajj starts at sunset (Mahgrib) on Sunday, but many have begun on the Saturday evening.

Pilgrims perform �Tawaf Al-Qudoom� at Mecca (initial round of circumambulation [the act of moving around a sacred object, in this case the cuboidal Kaaba at Mecca]) then move to Mina prior to midday. They sleep there and then move to Arafat after morning prayers.Temperatures were expected to reach 37-41� C yesterday and throughout the week.

Given a 14-day incubation period (most lengthy estimate), if the MERS-CoV is going to show up any differently among hajis this year than it did as a result of last year's Hajj (you may have noticed that no pandemic ensued), we should see those cases having presented with symptoms by 
Sunday the 27th. If we really want to get a feel for how easily transmissible this virus is, then this is the opportunity to observe and test.

Of course, this is an artificial date, given pilgrims have been assembling and mingling for some time during the lead-up to Sunday evening, but I'm using that date as the outer limit for appearance of symptomatic cases using a timepoint in which many people definitely congregated together in large numbers.

We may also see a rise in cases appearing outside the KSA as retuning pilgrims picking up infection just before they depart, become symptomatic on home soil. Or we may not.

Thanks to FluTrackers for posting this link.

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