Qatari camels clear coronavirus

The camel herd that was previously Middle East respiratory syndrome coronavirus (MES-CoV) RT-PCR-positive is no longer positive for viral RNA according to an OIE report (OIE=Office International des Epizooties; the world organisation for animal health).
In there report they note that retesting of the herd, subsequent to the initial testing presumably, has yielded no positive this time around.

So it looks like the MERS-CoV infection is an acute infection (it is contracted, it causes illness - perhaps - and then it goes thanks to an immune response - perhaps), as are many/most) viral infections of animals and humans.

An interesting comment within the report states that...

The planned massive survey for MERS-CoV in animals is under implementation and the same herd is under systematic retesting. Follow-up reports will be submitted when there will be new data.

I do like a statement that includes the words "massive study" in it!

Hat tip to CIDRAP.

Influenza A(H7N9) virus case accumulation for 2013...

Click on image to enlarge.

Sure a full 12-months of H7N9 in humans hasn't passed yet, but 2013 is coming to a close. 

I have 148 H7N9 cases worldwide including deaths and the asymptomatic boy from Beijing who seems to still be off the official tallies for some reason. WHO have not had an official tally of fatal cases in their recent 2 disease outbreak news posts, the last with a tally was 6-Nov in which 45 deaths were recorded with 6 cases remaining in hospital and 88 having been discharged. Hong Kong's Centre for Health Protection (CHP) maintains a running tally of mainland China cases With the recent death of a Hong Kong man the tally of fatal cases rest around 46 (PFC of 31.1%).

I've just changed my spreadsheet to a weekly format from the daily version and the first chart it reveals is shown above. 

This includes the lay of the land for all H7N9 cases from the beginning of the outbreak, 11-Feb (date of pneumonia for son of index case), through to 29-Dec. Date data employ dates of reporting if no date of illness onset could be found.

We can see from this 47-week inclusive dataset that the principle period of activity was in late March to late April. Whether that will also be the case in the new year is anyone's guess really.

What we can say from the vast amount of influenza virus research data in the scientific literature, is that each and every new combination of 8 gene segments that comprise a distinct influenza A virus seem capable of their own distinct "personality".

What to watch for with human parechovirus (HPeV) infections...

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Merry Xmas and Happy Holidays 2013

Hi All,

Just a quick wish from me to you for a Happy Xmas time.

If you are lucky enough to have been born into a wealthy country, enjoy your good fortunes and have a very festive and well-fed time with friends and family over the next few days. 

But please also spare a thought for the many more people on the planet who have a much harder road to travel each and every day. Perhaps add substance to that thought with a last minute present in the name of some of your loved ones, gifted to a charity that can help. This year I am supporting  UNICEF via their excellent range of charity gifts. Polio vaccination kits will be in a couple of Xmas stockings this year!

All the very best for a safe, happy, prosperous (well-funded) 2014.

Ian 
Editor-in-chief,
Virology Down Under

Middle East respiratory syndrome coronavirus (MERS-CoV): camels, camels, camels!

Two studies in Eurosurveillance, an editorial note, A Lancet Infectious diseases report and a comment point 2 hairy toes toward camels as a harbour and source in some capacity, for MERS-CoV, or MERS-CoV-very-like, infections ticking over around the Arabian peninsula. All in the space of a week!

First up, Hemida and colleagues from Saudi Universities, China and the United States describe the search for neutralizing antibodies in animals in a 12-Dec Eurosurveillance article. Great to see Saudi Uni researchers involved. I've mentioned this virus neutralization assay and its intent before. This new study builds on that from Perera and colleagues who looked at camels and some other animals.

Some major findings from this study include:

• Dromedary camels (n=310), sheep (n=100), goats (n=45), cattle (n=50) and chickens (n=240) from MERS-CoV hotspots in Saudi Arabia (Riyadh and Al Ahsa) were tested with the pseudoparticle neutralization (ppNT) test
• 280 camel sera (90% of camel sera) were positive using the MERS-CoV ppNT test. No other animal sera reacted in this test
• 96% of camels had MERS-CoV (or a close relative)-reactive antibodies by 1-year of age; two-thirds of camels that were younger than 1-year of age reacted, which suggests acquisition of these infections accrues rapidly during that 1st year, or maternal antibodies remain in the offspring
• 54 randomly selected camel sera (18% of all camel sera) were diluted out and tested using ppNT and a standard MERS-CoV microneutralization test (MNT). High levels of calf antibody specific to BCoV did not block MERS-CoV infection nonetheless there were some similar titres to both viruses in some of the camel sera. A ≥4-fold higher amount of antibody reactivity towards 1 virus compared to the other defined which was the most likely virus reacting. It's possible (likely?) that camels have "seen" (been infected by) both viruses or similar viruses at some time. Some of the subset of camel sera had high levels of antibody only to MERS-CoV (or a close relative)
• Cows did not have any sign of MERS-CoV-reacting antibodies in their sera; they did have BCoV reactivity though
• It was not stated whether the camels were ill or healthy at sampling

So other animals were not neutralising-antibody positive but young Saudi camels, like Omani, Spanish [retired to the Canary islands] and Egyptian camels before them, had acquired and reacted to infection by MERS-CoV (or a close relative) according to these validated antibody-detection tests. Regular sampling of an animal cohort is one suggested future direction.

Secondly we have Reusken and colleagues from the Netherlands, Jordan and Germany look at animals from the first known site to harbour MERS-CoV infections in April 2012 at a hospital in Zarqa city in Jordan. This was published online 12-Dec in the same issue of Eurosurveillance. Just fyi, Prof Marion Koopmans is senior author on this study and on the study below.

Some of the key points include...

• Sera from 3-14-month old dromedary camels (n=11), goats (n=150), sheep (n=126) and cows (n=91) were tested by an antibody microarray method, used previously by this group, and the results confirmed by identifying antibodies with the ability to neutralize MERS-CoV infection.
• The lower levels of antibody than seen in an earlier study may reflect leftover maternal antibody protection, although the authors note than maternal camel antibodies wane within 2-months of birth and that adult camels had higher levels of antibodies
• This study cited a reference noting that apart from cows, camels, goats and sheep are major sources of meat and milk in the region, ~1 sheep/pilgrim or ~1 camel/7 pilgrims is slaughtered in Saudi Arabia for the Hajj which equates to ~3,000,000 animals!
• 11/11 camel and 6/126 sheep sera had antibodies that reacted with MERS-CoV but, in additional testing, the sheep sera were not able to neutralize infection by MERS-CoV
• 23/91 cows and 128/150 goat sera reacted with the human CoV, OC43 (antigenically related to BCoV); no sera reacted with SARS-CoV
• A broadly reactive CoV, or "pancoronavirus", PCR method was used to screen camel faeces; 3 BCoV sequences were obtained, but no sign of MERS-CoV RNA in the faeces hinting that there was not an active infection at the time of sampling. This last point assumes that MERS-CoV is excreted from the camel gut during/after an acute infection. The next study may not support that assumption.
• It was not stated whether the camels were ill or healthy at sampling

Add young camels from Jordan to those from Saudi Arabia, Oman and retired Spaniard animals as possibly having been infected by MERS-CoV (or a...you know, similar thing) or at least having antibody acquired from their mothers. 11/11 POS may yield some more data to narrow down the age of acquisition; 3-months and seropositive could suggest MERS-CoV acquisition at or very close to birth, or simply remaining protective maternal antibody. Perhaps camel farms and farmers should be a next stop for detailed testing. 

In an Editorial note, the Eurosurveillance Editors note that these data do not define the primary source for human acquisition is still unclear.

Thirdly we have Haagmans and colleagues from the Netherlands, Qatar and the United Kingdom describing the study of the Qatari farm camels and temporally related human infection, from which MERS-CoV was detected back in late November. This article was published online by the Lancet Infectious Diseases (17-Dec).

Some key findings here include...

• The article's introduction suggests that the genetic diversity of human MERS-CoV viruses determined to date is the result of multiple zoonotic acquisitions 
• This study started with a 61-year-old Qatari male (61M; FT#144) farm owner who had not travelled outside Qatar and his 23-year-old male (23M; FT#150) employee
• 61M was RT-PCR POS (upE assay) on a sputum sample (collected Oct-13) and 23M on a throat swab (collected Oct-17) and subgenomic (ORF1b and nucleocapsid [N]) sequencing at the Public Health England confirmed the detection to be MERS-CoV
• MERS-CoV genomic sequences from the 2 human cases were placed on GenBank and called Qatar_3_2013 [61M] and Qatar_4_2013 [23M] as were camel sequences from the subsequent experiments
• Sera, rectal swabs and flocked nasal swabs were collected from all of the farm's 14 camels as well as 5 stool samples from 3 cages, by a team wearing personal protective equipment. Samples were shipped to the Netherlands for upE, N and ORF1a RT-PCR testing
• Vero and Huh-7 cells were inoculated with swabs that had been added to viral transport medium onsite. A single culture from Camel#7 was upE RT-PCR positive at day-4 after inoculation but no culture yielded infectious virus
• 5/14 camel nose swabs were MERS-CoV PCR positive using upE, N and ORF1a assays
• Sequencing of a fragment of Spike gene yielded 100% identity with other Saudi MERS-CoV sequences; sequence only differing by 1 base from the original isolate, MERS-CoV/EMC.
• All camel sera were antibody positive using an immunofluorescence test on MERS-CoV/EMC-infected cells
• There was no "direction" to the acquisition of MERS-CoV. Whether the camels infected the humans or the humans infected the camels could not be determined from this outbreak
• The authors conclude that detailed cases histories are important to identify animal exposures. These might not otherwise be though important in a cursory question and answer of a patient, their family or contacts

This study adds very important data that indicate a recent or resolving MERS-CoV infection in camels. No positivity was found from gastrointestinal samples. Despite no isolation of infectious MERS-CoV, the detection of RNA is an acceptable surrogate for the presence of "live" virus in an animal or person (even if it could not propagate in vitro). So the camel story has some very important new chapters added in this series of studies.

In a Comment in LID, Ferguson and Verkhove note how the One health concept is exemplified by not only this publication; as it has been by the entire MERS-CoV story. The comment also notes the need for much more study, passive and active surveillance of human and animal disease/movements and better and faster reporting to link these, or any other, animals back to the cases that are spread across a very broad geographic region. They hold Haagmans and colleagues' article up as an example of how to get more answers and prevent sustained MERS-CoV transmission among humans from developing in the future.

Tracing and testing camels imported into the region from Africa for use as food may also open a new front to identify the transmission potential of MERS-CoV (or a similar beastie) in camel infections. Testing of pneumonia causes at these other sites both for virus and antibodies against virus is probably also warranted. 

As usual, new data bring new questions and so many papers in only a week makes for lots of questions. 

Little rhino...

To the tune of ‘I’m a little teapot’

I’m a little rhino,

Strain in doubt

Bind with my canyon

Bind without

When I’ve replicated

Just the right amount

You’ll need to get a tissue to blow me out

[alternate: exacerbate your wheezing and cough me out]

Thanks to Cassandra Faux for putting this one together back in 2007.

Twelve weeks of childcare...

To the tune of the twelve days of Xmas

In the first week of childcare,

some kids got sick with me

The lab said they might have HRV

In the second week of childcare,

some kids got sick with me,

Two had paraflu,

and a few might have had an HRV

In the third week of childcare,

some kids got sick with me,

Three had an entero

Two had paraflu

and a few had uncultivable HRV

In the fourth week of childcare,

some kids got sick with me,

Four had OC43

Three had an entero

Two had paraflu

and a few had untypeable HRVs

In the fifth week of childcare,

some kids got sick with me,

Five had MPV

Four had OC43

Three had an entero

Two had paraflu

and a few had something like an HEV

In the sixth week of childcare,

some kids got sick with me,

Six had HKU1

Five had MPV

Four had OC43

Three had an entero

Two had paraflu

and a few had newly identified HRVs

In the seventh week of childcare,

some kids got sick with me,

Seven had an adeno

Six had HKU1

Five had MPV

Four had OC43

Three had an entero

Two had paraflu

and a few had pleconaril-resistant HRVs (we think!)

In the eighth week of childcare,

some kids got sick with me,

Eight had bocavirus

Seven had an adeno

Six had HKU1

Five had MPVs

Four had OC43

Three had an entero

Two had paraflus

and a few were PCR-positive for HRV

In the ninth week of childcare,

some kids got sick with me,

Nine had RSV

Eight had bocavirus

Seven had an adeno

Six had HKU1

Five had MPV

Four had OC43

Three had an entero

Two had paraflu

and a few had antigenically distinct HRVs

In the tenth week of childcare,

some kids got sick with me,

Ten had NL63

Nine had RSV

Eight had bocavirus

Seven had an adeno

Six had HKU1

Five had MPV

Four had OC43

Three had an entero

Two had paraflu

and a few had more than a single HRV

In the eleventh week of childcare,

some kids got sick with me,

Eleven had Wuv and Kiv

Ten had NL63

Nine had RSV

Eight had bocavirus

Seven had an adeno

Six had HKU1

Five had MPV

Four had OC43

Three had an entero

Two had paraflu

and some came from a clade of HRV (which was distinct!)

In the twelfth week of childcare,

some kids got sick with me,

Twelve had IFAV

Eleven had Wuv and Kiv

Ten had NL63

Nine had RSV

Eight had bocavirus

Seven had an adeno

Six had HKU1

Five had MPV

Four had OC43

Three had an entero

Two had paraflu

and a few had what we call HRV C

Thanks to Katherine Arden and Cassandra Faux for helping me put these together back in 2008.

You're the virus I got...

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The Bocavirus...

To the tune of Copacabana

Its name was boca, it was a parvo
No membrane just a shell, a tiny genome n’ there as well
It was found worldwide, but first in Sweden
And while it might yet be a star, its role remains unclear by far

Around a crowded globe, its mode of spread unknown
It was newly found and yet endemic
PCR helped show

Call it boca, the bocavirus
Quite close to a dog and cow virus
Call it boca, the bocavirus
Coughing and sneezing, expiratory wheezing
But the boca, was it a cause?

Its name was boca, and just this year
It was found in blood and stool, but isolation did not ensue
Although with EM, something was seen
And now systemic is where it’s at, PCR alone is falling flat

And so more questions flow, we still have far to go
Most often found with another virus
Co-detections rule!

Call it boca, the bocavirus
Quite close to a dog and cow virus
Call it boca, the bocavirus
Pneumonia and sneezing, expiratory wheezing
But the boca, its everywhere

Its name is boca, it raises questions
But two years later on, no real answers have been found
It is a virus, on that we’re certain
Still reports from far and near, describe detections everywhere

Sequences don’t change much, although two clades show up
We need more trials and more controls
But will that be enough?

Call it boca, the bocavirus
Quite close to a dog and cow virus
Call it boca, the bocavirus
Gastro and sneezing, expiratory wheezing
What does the boca, do to us?

Thanks to Katherine Arden and Cassandra Faux for helping me put these together back in 2007/8.

FluTrackers needs your help....HELP THEM!!

I've written before about how much we smaller bloggers and interested other parties rely on FluTrackers to be the rock on which we can rely. Have a quick read of that post here.

FluTrackers are a bunch of volunteers who self-fund the computer infrastructure that houses and serves us with the carefully agglomerated rantings of a seemingly endless stream of information sources on all manner of infectious disease happenings, from all over the world; almost instantly in many cases. There's a very good chance that if it made it onto any website anywhere, then that information has been read and filtered and posted by one of the very few super-diligent FluTrackers newshounds.

I cannot imagine, even if blogging was not only a part-time hobby for me, how I would ever manage to do what FluTrackers manages.

Over 50,000,000 page views this year provide ample data to indicate that they perform a service that is of considerable value to many. 

FluTrackers punches very far above its weight in the complex, fast-paced world of infectious disease communication. I frankly don't know how they do it for the price - which, of course, is borne entirely by them.

So it comes to this time of year when we see a request from the crew at FluTrackers for some financial aid from us - some of those millions of page viewers. If only a tiny fraction of us were to donate $10 (that's a tub of Sara Lee ice cream in my neck of the woods), FluTrackers would be able to fund themselves for many a day.

So come on guys - help keep the FluTrackers tracking flu...and rhinovirus...and bocavirus...and respiratory syncytial virus...and parechovirus...and enterovirus (including poliovirus)...and parainfluenzavirus...and adenovirus...and staphylococcus...and unusual spikes in hospital admissions...and pneumonia cases... and emerging diseases...and emerging viruses...and disease outbreaks...and tuberculosis and...far too many more other things to list.

I might now be $10/poorer for each user that reads/uses the data in my own household, but I'll be exponentially more enriched in 2014 for the data I know they will (hopefully continue to) provide to the world's amateur and professional disease trackers and the public-at-large. 

Read more about where this paltry amount of money will go from FluTrackers themselves.

And more from Mike Coston's blog here on the Cost of fluing business.

Randall the red-nosed toddler...

To the tune of Rudolph the red-nosed reindeer

Randall the red-nosed toddler
Had a very runny nose 
Asthma exacerbation 
Fever adding to his woes 

All of the other toddlers 
Didn't have immunity 
They all came down with symptoms 
Differing in severity 

Then one group of researchers 
Virus-hunting was their game 
Swabbed, extracted, amplified
A rhino POS of course was spied 

Randall’s rhino was sequenced 
Turned out to be rhino C
Randall the red-nosed toddler
Just a 'common' cold indeed!

Randall the red-nosed toddler

Had a very runny nose 
Asthma exacerbation 
Fever adding to his woes 


Thanks to Katherine Arden and Cassandra Faux for helping me put these together back in 2008.

More confirmation that rapid influenza diagnostic tests (RIDTs) should be used in context

The Texas Department of State Health Services have a useful couple of paragraphs from an Influenza Health Alert that puts into context reliance on the convenient and rapid, but ultimately intensive rapid influenza tests.

Rapid Lab Tests: Rapid Influenza Diagnostic Tests (RIDTs) can be useful to identify influenza virus infection, but false negative test results are common during influenza season. Clinicians should be aware that a negative RIDT result does NOT exclude a diagnosis of influenza in a patient with suspected influenza. When there is clinical suspicion of influenza and antiviral treatment is indicated, antiviral treatment should be started as soon as possible, even if the result of the RIDT is negative, without waiting for results of additional influenza testing.

Mike Coston also has an excellent article touching on some of the many other viruses that can cause influenza-like illness and on rapid testing, over on his blog, Avian Flu Diary. I highly recommend it.

Cost is always an important factor when hospitals and attached diagnostic laboratories consider how to address infections. Rapid turnaround time is another major cost because, for those small number of viruses with this option available, an antiviral drug can be administered and there seem to be benefits from doing this as early as possible for severe influenza. In some cases of course, a vaccine is available to block severe disease from occurring when you get infected (they don't stop infection, but a response to a vaccine is much safer than a bad response to an actual virus infection, as we've seen in the recent media for H1N1 in Texas. 

During flu season, influenza virus is an obvious cause for a spike in hospital admissions for acute respiratory symptoms - but if confirmation of that pathogen relies on a testing platform that can miss a third of infected individuals (only 17/45 PCR positives were detected by am RIDT in Ref#2) then antivirals may not be used in time. In a more recent comparison of RIDTs using PCR results as the standard, viral load in the upper airway (less virus gave fewer positives - duh), age (the young and elderly were less often positive), presentation time (sampling >2-days after onset of illness reduced the proportion of positivity), virus type (less sensitive for subtype B infections than A) and whether there was pneumonia or not (the former were less often positive perhaps reflecting less viral replication in the upper airway than in the lower airway?) were factors in how well the antibody-based RIDTs performed. Sensitivity ranged from 50% to 94%. These 2 studies used samples from the upper airways (swabs or nasopharyngeal aspirates respectively, as suggested by the BD™ Directigen EX Flu A+B assay, Alere™ Influenza A & B Test and the QuickVue® 117 Influenza A+B test)

In these instances, PCR-based methods (used as the "gold standard" in those published evaluations) shine but they take longer to generate a result and require more expertise to conduct than a rapid test. The slightly longer time is not just because they take hours to conduct instead of the minutes of a rapid test (remembering that viral lab diagnoses used to take days not hours) but because lab testing is only part of a process which also involves paperwork and passing verified and signed off results and information to all concerned clicnial parties and patients. That can take more time-and sometimes be a bottleneck for result release. Its hard for a patient's family and friends to wait, but the results will be that much more reliable when they come.

A feature of influenza season is the concurrently reduced levels of activity of other viruses. Influenza tends to "push out" a lot of other viruses during it's peak season - probably reflecting influenza's ability to dominate the immune response in an infected individual, and by extrapolation, reduces the number of susceptible individuals at the community level, remembering that the majority of influenza cases are acute upper respiratory tract illnesses.

So it looks more like the Montgomery County deaths may have been due to the high levels of influenza A(H1N1)pdm09 virus generally circulating in them there parts. A KHOU news outlet report, also circulated on ProMED, suggest that 4 Montgomery county deaths were due to H1N1, as well as other sine the regions. However, the Montgomery County Public Health District reports only 2 H1N1-confirmed deaths, so things are still a little confusing there. And as for whet other viruses may also be in these patients...so far, who knows?


A brief guide to some terms used in these sorts of discussions (also from Ref #2 below)

Sensitivity
No. of true positives / no of true positives and false negatives

Specificity
No. of true negatives / no of true negatives and false positives

Positive predictive value
No. of true positives / no of true positives plus no. of false positives

Negative predictive value
No. of true negatives/ no of true negatives


References and further reading...

1. FluTrackers story. http://www.flutrackers.com/forum/showthread.php?p=517368#post517368
2. Accuracy of rapid influenza diagnostic test and immunofluorescence assay compared to real time RT-PCR in children with influenza A(H1N1)pdm09 infection. http://www.ncbi.nlm.nih.gov/pubmed/23175329
3. Clinical and Virologic Factors Associated with Reduced Sensitivity of Rapid Influenza Diagnostic Tests in Hospitalized Elderly and Young Children. http://www.ncbi.nlm.nih.gov/pubmed/24285739

Texan flu step: flu-like illness outbreak in Montgomery County [UPDATE #2]

Click image to enlarge.
County of Montgomery highlighted in red.
From Wikipedia

While 1,920 influenza-like illnesses (briefly that's measurable fever plus one or more particular symptom usually; includes sore throat, fatigue, body aches and complications including pneumonia) have occurred in this county since the start of the local influenza season, 8 severe infections (all with pneumonia) in adults (41-years to 65-years old) have been admitted to 1 (?) facility. These 8 cases are not all testing positive for the "common" influenza virus types. Initial testing may have been by rapid "bedside" influenza test which are known for their lack of sensitivity. PCR testing would be preferred, if that wasn't used.


According to the US Centers for Disease Control and Prevention website, seasonal influenza's populations at greatest risk of severe disease usually include the very young (under 5-years) and older adults (>65-years), pregnant women and indigenous populations, and those with a range of pre-existing medical conditions.

4/8 cases died and none of the fatal cases were vaccinated against influenza (?survivors were vaccinated). Kidney issues have also been reported according to a video report at the Houston Chronicle.

1/4 surviving case has tested positive for influenza A(H1N1)pdm09 virus, which is circulating locally as the annual flu season is well engaged in the region. 2 other survivors have tested NEG for all influenza viruses and have been sent on to the CDC. Test results are outstanding on the other survivor.

Click on image to enlarge.
2013-14 Influenza season data from FluView, CDC at
http://gis.cdc.gov/grasp/fluview/main.html.
Of those 221 antigenically subtyped by the CDC,
184 are H1N1 2009.

Management steps include staying away from ill people, hand-washing using soap and water/alcohol-based hand rubs, covering coughs and sneezes, staying at home when ill, cleaning linens, eating utensils and dishes used by ill people, and wiping down frequently touched surfaces if likely to be a landing spot for virus from an ill co-habitant/co-worker/school or daycare child.

It would be interesting to know what testing has been employed for influenza and what other respiratory viruses and bacteria have been tested for and excluded because, despite some enthusiastic but highly misleading and inflammatory guesswork, there are not yet enough data to identify an infectious aetiology for this pneumonia cluster. I'm sure in a busy environment like this, work is progressing on many levels to resolve the mystery. Since at least 2 of the 8 patients have tested negative for influenza viruses, it is premature to extrapolate from the 1 positive case that H1N1 is the cause of all cases; it may be but those results are not yet in.

References...

• CIDRAP story. http://www.cidrap.umn.edu/news-perspective/2013/12/texas-health-officials-probe-severe-flu-illness-cluster
• Montgomery County Public Health on Facebook page. https://www.facebook.com/mctxpublichealth
• FluTrackers page. http://www.flutrackers.com/forum/showthread.php?t=214964
• Fox Houston. http://www.myfoxhouston.com/story/24257668/the-return-of-h1n1

Influenza A (H10N8) virus, the new kid on the block...

Click on image to enlarge.

Step by step we seem to be getting familiar with the entire influenza spectrum of naming combinations and permutations. When you consider that even 2 influenza viruses with the same common naming scheme (like H7N9) may have completely different evolutionary histories and clinical impact, well, influenza is a tough act to follow epidemiologically.

The latest, called H10N8 was detected in a human (73-year old female) for the first time Dec-6th. H10N8 has been found in the environment in the past.

The woman, who had visited a live bird market, died from respiratory failure following pneumonia, although whether that was due to H10N8 infection is not clear. The woman was treated in hospital in Nanchang, Jiangxi province from Nov-30; she also suffered a heart attack, was immunocompromised, had high blood pressure and a neuromuscular disorder.

Hong Kong's Centre for Health Protection (CHP) urged travellers to stay away from live bird markets and to avoid contact with the birds/poultry and droppings.


As CIDRAP noted, low pathogenicity avian influenza A(H10N7) virus has been reported in 2 Australian adults processing chickens during an outbreak of the virus in 2010 and reported in 2 Egyptian infants (1-year old) possibly linked to market ducks during late April 2004.

h/t to crofsblog and CIDRAP.

A new rhino type is coming to town...[corrected]

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Flu bad, MERS a diversion?

In an "Infection hot topic" article in Clinical Microbiology and Infection, the Editor, Prof. Didier Raoult writes of the importance of not letting our excessive pride or self-confidence drive our desire to understand a rare and poorly transmissible (slowly-growing epidemic?) virus like the Middle East respiratory syndrome coronavirus (MERS-CoV) and distract us from "real infectious disease epidemics that are well known" at times of mass gatherings like the Hajj.

Because why not?

He notes that the recommendation for influenza vaccination during the recent Hajj probably prevented thousands of influenza cases and that 9% of returning French pilgrims returned an influenza virus positive throat sample. An example of some good communication then.

I wasn't aware that the scientific press, World Health Organization or governments had dropped any other balls in order to give MERS the attention any potentially new human pathogen, with or without pandemic potential, well and truly deserves.

I guess in hindsight, it might look like a lot of wasted effort went into MERS-related reporting. Readers of this blog would be aware of my own opinion on that matter - not nearly enough effort has gone into solving a number of questions about the MERS-CoV and certainly not enough data has been described and reported to make it easy to track and present new cases.

Far from being distracted, the developed nations have continued their fight against flu (so long as their governments aren't shut down), reporting heavily on it and other vaccine preventable diseases that are reappearing in the population (measles and polio for example). Many science communicators of all types in many locations around the world have also been discussing and describing in detail the oncoming wave of antibiotic resistant bacteria and many other viral and bacterial pathogens that can be considered rare depending, on the denominator you choose at the time. SARS-CoV infections were pretty rare (~8,200 confirmed cases) but the social, economic and healthcare impact of that little outbreak was incredibly disproportionate. Or perhaps it was perfectly proportionate? Remembering the SARS outbreak began in the dark without suitable coverage and communication to illuminate the early stages. 

What is the evidence that reporting on MERS has displaced any other efforts to monitor, debate or describe more endemic human infectious diseases?

Thankfully Prof. Raoult didn't call out the scientific community who are working hard to add new knowledge about "rare" human infections; work that will hopefully ensure they stay as rare as possible, for as long as possible if they are not halted at the source forever. 

I'm personally in no rush to read the bazillion Editorials that will follow in the wake of a pandemic due to infection by MERS-CoV, H7N9 or any other viruses with "little known effect on the human population".

Hindsight can be a harsh mistress but communication fosters preparedness.

New MERS-CoV genome sequence on GenBank...

I'm a little bogged down in my day-job for lots of posts just now (and too busy at nights hanging Christmas lights at home!) but just thought I'd post about the latest Middle East respiratory syndrome coronavirus complete genome sequence that's dropped onto GenBank.

It was submitted in October but came online 7-Dec.

I've added in the likely FluTracker's case number - this is the nearest match to the collection date but it may be from the index case (FT#31); both detected in France, the former form the United Arab Emirates.

Key features...

• Name: Middle East respiratory syndrome coronavirus isolate FRA/UAE, complete genome 
• Date of sample collection: 7-May-2013, France
• Sequence length: 29,901nt
• MERS-CoV case: FT#34; 
• GenBank accession number: KF745068
• Link: http://www.ncbi.nlm.nih.gov/nuccore/KF745068.1
• Authors: Enouf,V., Briand,D. and van der Werf,S.
• Virus sample source: Vero cell culture isolate
• Sequencing type: Sanger

Editor's note #12

Click on image to enlarge.
Latest H7N9 map.

VDU's Editor-in-Chief (okay it's just me - I also get coffee and sweep up the keyboard at the end of the day) was asked to comment on the recent influenza A (H7N9) virus case in Hong Kong.


See Bloomberg's latest article here.

“Respiratory viruses do their own thing; they don’t respect boundaries,” said Ian Mackay, an associate professor of clinical virology at the University of Queensland in Brisbane, Australia, in a telephone interview. “It does seems that it’s continuing to add to provinces and regions, rather than reappear in all the old places it started in back in February and March.”

References...

1. http://www.bloomberg.com/news/2013-12-02/hong-kong-confirms-city-s-first-human-case-of-bird-flu.html

Rhinovirus transmission by aerosol and lower respiratory tract disease after inoculation

In the next instalment to answer the question posed in last week's post, we also find that rhinovirus can a lower respiratory tract infection (LRTI), if it is delivered directly to the site; several issues around this topic are contentious in current age of PCR diagnosis of lower respiratory tract disease using specimens from the upper respiratory tract (URT).

From Thomas R. Cate et al, Am J Epidemiol.

Author: Thomas R Cate et al
Journal:  Am J Epidemiol 81(1):95-105
Year: 1965
RV type used: NIH 1734 (RV-A15¹)
RV receptor type: major group; ICAM-I

This study set out to investigate the impact of RV on the lower respiratory tract.

Key features of the study layout..

• 16 healthy adult male inmate volunteers
• Safety-tested preparation of RV-15
• 6 volunteers given 1ml nasopharyngeal serum-inactivated virus via a hand atomizer (coarse droplets expected to mainly deposit in the upper respiratory tract), and 1ml instilled intransally by pipette with subject lying on back
• 8, RV-15-antibody-free volunteers were exposed to 10l of air (16, 20 or 66 TCID₅₀ RV15), via a mask, containing 15-second-old 0.2-3.0um particles generated from a Collison atomizer (see Figure)
• A number of re-inoculations were also performed on each virus-delivery group
• Aerosols was also sampled using a Shipe impinger (this device contained cell culture medium onto which some aerosol was impacted) for virus isolation, after storage at -70°C. These data determined the dose that had been used
• Prior (2-days) to inoculation, nasal, pharyngeal and anal swab specimens and 10ml of nasopharyngeal wash (NPW) were collected, frozen at -20°C for testing to identify pre-existing viruses or bacteria (all culture based). The same specimen types were collected after inoculation (minus the anal swab). RV culture was conducted on human embryonic fibroblast cultures, with rotation at 33°C)

Key results included...

• Only 1 other virus, apart form RV-15, was found in the subjects. Culture may have missed fastidious or unculturable respiratory viruses (like the RV-Cs) however.
• During the 1st week after inoculation, usually starting from day-2..
• NPWs contained culturable virus in at least 1 specimen from 8/8 subjects
• During the 2nd week after inoculation..
• 7/8 subjects gave virus-positive NPWs
• During the 3rd week after inoculation..
• 5/8 subjects gave intermittent virus-positive NPWs
• Maximal virus titre aligned in time with most severe illness
• Nasal and pharyngeal swabs specimens did not yield virus as often as NPWs
• All subjects had a rise in antibody titre of 4-fold or greater, indicating infection, by 3-weeks with a further bump after 4-5-weeks
• Tracheobronchitis was diagnosed in 6/8 antibody-free aerosol-inoculated volunteers. This is a lower respiratory tract disease.
• Signs and symptoms included cough (sometimes in fits), substernal chest pain,, wheezing, tender trachea.
• 3 had a primary diagnosis of tracheobronchitis , the other 3 also had a prominent coryzal illness (nasal obstruction/discharge, sneezing, sore throat, swollen neck lymph nodes). 
• Fever was determined in 5/8, within the 1st 1-2-days.
• Signs and symptoms lasted for 1-4 days, a little longer for a rhinitis-alone
• No tracheobronchitis developed among 31 antibody-free volunteers inoculated through a course spray/drop method into the nasopharynx
• No infection (no suitable rise in antibody) or illness was detected among 6 volunteers inoculated with a preparation of virus that had first been inactivated by incubation with an antibody-positive serum. This identified that there were no other viruses/bacteria in the preparation that could have caused the disease. This had been, infrequently, found in other preparations by the authors so this step was important part of their comprehensive approach.
• 4-weeks later, 2 volunteers from the aerosol infection group, 2 from the inactivated virus group, and 2 new volunteers, were (re-)inoculated
• No infection, illness or virus shedding resulted in the aerosol pair
• No illness but infection and shedding occurred in the pair previously inoculated with inactivated virus
• Infection, illness and shedding were apparent in the new volunteer pair
• Neutrophil counts were significantly raised in aerosol-inoculated volunteers at illness onset and also, but to a lesser extent, in the 6 volunteers given inactivated virus. This explains to me why in those with a predisposition to severe RV outcomes, including those with asthma, a symptomatic RV infection is not necessary to trigger an attack.

The authors concluded...

• The aerosols generated here, which carried relatively small amounts of virus, would likely travel beyond the nasopharynx and tracheobronchial tree and be carried into the lungs, probably with <50% deposited and the remainder exhaled
• No evidence of pneumonia was found
• If RV is suitably aerosolized in sufficiently small particles, inhalation can result in lower respiratory tract disease while site-specific installation into the upper respiratory tract usually results a typical URTI or "common cold"

How do these findings translate to everyday exposures to RV coughs and sneezes and in children? In the general community we are constantly exposed to virus and have a complex, person-specific panoply of antibodies resulting from different infections beginning in childhood. This is probably why we are incapacitated by bad colds and LRTIs all the time! An addendum in the discussion of Cate's paper highlights how symptoms resulting from RV infection are best considered as part of the entire spectrum of possible outcomes. 

Previous symptomatic infection, as shown above, protects from lower respiratory tract disease hence adults are less likely to have LRTIs than children who see these viruses for the first time. Also, there is literature showing that the antibody to some RVs can protect against, or moderate, disease due to infection by other RVs. If you are antibody-free, then disease can potentially be more severe.

Cate's studies are all conducted without knowledge of the 50+ RV-Cs because they could not be grown (detected) using the cells employed by the culture methods of the day. Why is that relevant? Because some consider RV-Cs to be more asthmagenic/pathogenic and because we don't know the receptor or natural tissue tropism/distribution of the RV-Cs in humans. How the RV-Cs perform in human volunteer infections is unknown.

Certainly room remains for some new research building upon excellent studies like this one by Cate et al and highlighting (a) that RV can infect the lungs and cause disease if an aerosol is encountered and (b), that one outcome from RV infection does not fit all.

Further reading and references...

1. First HRV nomenclature assignment publication
   http://www.nature.com/nature/journal/v213/n5078/pdf/213761a0.pdf