Research on MERS in South Korea seems fractured...

I would be remiss if I didn't point out that the Kingdom of Saudi Arabia (KSA) is not the only country that can be seen as slow to initiate local research on local cases of Middle East respiratory syndrome (MERS), MERS-coronavirus (MERS-CoV) or the epidemiology thereof.

The outbreak in South Korea began when an incubating person flew in from Qatar, arriving 4th May. He became ill while in South Korea, with symptoms beginning on the 11th May 2015. This was to become the largest MERS-CoV outbreak outside of the Arabian Peninsula and it is still to be investigated as the overarching single event that it really was. Scientific papers, letters, media and case reports all look at small groups of specimens, this or that specific hospital, a particular slice in time or an interesting group of cases and they reach a range of conclusions. But there appears to be no over-arching all-encompassing study of the outbreak. We did eventually see such a report from the KSA in its description of four dozen early MERS cases - 13 months after the first case became ill.[4] South Korea only had 185 cases in total (exporting one to southern China) so this should not be a great task.

A recent article in The Korea Times noted that "while the initial tests were conducted on a limited number of patients, research is underway to screen clinical specimens from 32 people that will help shed better light on the matter."[1] Well, perhaps a part of the matter. [1]
The article focusses on Spike gene mutations that were found in the MERS-CoV variants from 8 human cases - which is not a remarkable discovery and has been happening since we first saw sequenced MERS-CoV from humans (see "Tracking MERS-CoV through time: a spikey problem" [2]). 

The article also goes on to say that "There is a need to focus the country’s research capability on finding the reason for the change." Those will be dollars wasted since one cannot "find the reason" for a virus mutating because that is akin to asking why we exist. 

Scientific studies can determine that the variants have mutated at certain points and they can seek out whether those changes have any effect on the efficiency of viral replication, transmission or on our immune response to infection. This will be achieved by comparison to other non-mutated MERS-CoV variant viruses and will need more than one older variant to be included so as to encompass all of the different Spike gene mutations that have been determined to date. But these studies cannot find the reason for these mutations. Yes, that is a pedantic point.
We are about 6 months out from when the final MERS case first became ill in the South Korean outbreak. This media report sadly highlights that the world is still far away from seeing comparative experimental data defining whether or not there was anything special about the MERS-CoV variants in the outbreak. Strangely though, it has already been concluded that the rapid spread of MERS-CoV in South Korea was not due to viral changes but instead because of the poor control of transmission in healthcare settings.[3] That makes this report and its message to the public both a little stale and perhaps even unnecessarily alarming.

Clearly, the KSA was not alone in needing to improve its collaboration, communication and organization of research in response to the appearance of a new virus. 

References...

1. http://www.koreatimesus.com/mutation-detected-in-s-korean-mers-virus-govt/
2. http://virologydownunder.blogspot.com.au/2013/08/tracking-mers-cov-through-time-spikey.html
3. http://www.who.int/csr/disease/coronavirus_infections/situation-assessment/update-15-06-2015/en/
4. http://www.ncbi.nlm.nih.gov/pubmed/23891402

Zika virus disease (ZVD): 14 cases until 2007 then Yap island, Micronesia...

Update #1: 17JAN2016

Between the discovery of Zika virus (ZIKV) in 1947 and today's review subject, an outbreak on Yap Island,[1] there had only been 14 cases of Zika virus disease (ZVD) described. The keyword there is detected, or actively sought.

Some opinions on ZIKV...

In my opinion - and as the following study supports for this outbreak it describes - the confirmed ZIKV cases we heard of during 2014 are likely the tip of a vastly bigger iceberg of human infections. Many of the countries from which we have recent reports of "first" autochthonous (local) ZIKV transmission may well have had this virus in their midst for much (much, much, much?) longer since it often causes mild illness. Unless carefully looked for, ZVD is clinically very similar to other mosquito-borne virus infections. 

I hope that on the list of things to do to understand ZIKV - probably topped by investigating the suspected link between ZIKV infection and microcephaly) - is go back to stored human sera and look for traces of ZIKV or antibodies against ZIKV in these newly announced transmission zones. This will give us an idea of how long this virus has been around.

Yap Island ZVD outbreak in 2007...

In April and May of 2007, an outbreak of rash, conjunctivitis, subjective (not measured) fever, arthralgia, and arthritis occurred on an island group (the 4 Yap Islands; population ~7,400 in 2000) that comprise Yap State in the Federated States of Micronesia. Three initial patients tested positive for IgM antibodies that suggested recent dengue virus (DENV) infection (although IgM can be non-specifically triggered as a result of another infection). However. the doctors believed the symptoms were not due to DENV infection.

Samples were sent away to the United States Centers for Disease Control and Prevention and ZIKV RNA was detected in the sera of 10 of 71 (14.1%) symptomatic people using a specific reverse transcription polymerase chain reaction (RT-PCR) assay. Other viruses were considered but could not be detected using specific assays. These viruses included dengue, chikungunya, o’nyongnyong, Ross River, Barmah Forest, and Sindbis virus. The finding implicated ZIKV as the likely cause of the outbreak, and ZVD as the disease.

The result triggered a bigger investigation during which 185 suspected cases (including 49 confirmed and 59 probable) were further investigated. 66% of the confirmed and probable casess were female and these 108 people had a median age of 36y. The earliest infections occurred 15th April. Among 31 of the confirmed cases who reported symptoms, rash lasted for a median of 6d (2-14d) and arthralgia for 3.5d (1-14d). None had travelled outside of Yap.

Enzyme-linked immunosorbent assay (ELISA), an antibody detection method, was used to look for IgM antibodies indicating recent ZIKV or DENV infections. The identification of very specific infection-neutralizing antibody to these viruses was also sought and the level determined by using a plaque reduction neutralization test with a threshold value of 90% (PRNT₉₀). Antibodies to other flaviviruses were not sought in this study.

A case definition was created:

• A patient with suspected ZVD had acute onset of generalized macular or papular rash, arthritis, arthralgia, or nonpurulent conjunctivitis. 
• Blood samples were requested from acute phase ( within 10d after the symptom onset) and convalescent phase (14d later)
• A patient with probable ZVD had:
• IgM antibody against ZIKV
• ZIKV PRNT₉₀ that was still detectable at a dilution of (titer) at least 1:20
• A ratio of ZIKV PRNT₉₀ titre to DENV PRNT₉₀ titre was less than 4
• Either no ZIKV RNA detected by RT-PCR or a sample which was inadequate for the performance of RT-PCR
• A patient with confirmed Zika virus disease had:
• ZIKV RNA detected in their serum or 
• IgM antibody against ZIKV (detected by ELISA) and 
• A ZIKV PRNT₉₀ titre of at least 20 and 
• A ratio of ZIKV PRNT₉₀ titre to DENV PRNT₉₀ titre of at least 4. 

173 of 200 randomly selected households were surveyed yielding 557 blood samples of which 414 (74%) had IgM anti-ZIKV antibody detected and 156 of these recalled a relevant recent illness. Among those without any IgM detected, 27 also recalled a relevant illness. Extrapolation of these figures resulted in the authors estimating that 73% of residents were infected during this outbreak with 18% of those infected having a clinical illness likely due to ZIKV infection.

An examination of 1,366 containers holding water, frequently (43%) found that they also contained 9 species of mosquito larvae/pupae and such containers were present in 87% of households. [A simple intervention method is to tip these out and ensure they cannot refill with water]. Three other mosquito species were identified to as adult mosquitoes. Aedes hensilli was the most frequently identified mosquito species overall. 

No mosquitoes tested contained detectable infectious ZIKV (examined by cell culture methods) or ZIKV RNA (RT-PCR).

So, jumping forward from the 1940s to the naughties (2007), we see a major shift in the diagnostic arsenal which supported this study. It allowed us to see just how effectively a mosquito-borne virus can apparently consume an entire island community. I wonder what IgG results - generally interpreted to indicate older earlier infection by an agent - on these same sera would yield? Would they further support the author's conclusions that a viraemic human (infected individual with ZIKV in their blood) or a virus-infected mosquito had only recently arrived from somewhere else?

Could something have changed in the levels of the vector population/species resulting in a sudden surge in virus? 

The authors note that there had not been any previous disease outbreaks of this sort reported on Yap-but were isolated cases occurring earlier? Had the virus been slowly smoldering in rare transmissions from mosquito to human/other animal to mosquito etc, for a while before building up speed and manifesting as an outbreak?  Why did none of the tested mosquitoes contain traces of ZIKV virus? 

It is also worth noting that many ZVD "cases" described in more recent months may be better defined as "suspect" and not yet confirmed. But I stand to be corrected on that.

References...

1. Zika Virus Outbreak on Yap Island, Federated States of Micronesia
   Duffy MR, Chen TH, Hancock WT, Powers AM, Kool JL, Lanciotti RS, Pretrick M, Marfel M, Holzbauer S, Dubray C, Guillaumot L, Griggs A, Bel M, Lambert AJ, Laven J, Kosoy O, Panella A, Biggerstaff BJ, Fischer M, Hayes EB.
   N Engl J Med. 2009 Jun 11;360(24):2536-43. doi: 10.1056/NEJMoa0805715.
   http://www.nejm.org/doi/full/10.1056/NEJMoa0805715

Updates...

1. Added 18% figure to clinical illness from population extrapolations in this paper

The third outbreak of influenza A(H7N9) virus seems to be over...

Cumulative curves of reported H7N9 cases and deaths in humans.
Click on graph to enlarge.

By the looks of the curve on the right, the rush of cases that defined the third known outbreak of the low pathogenicity avian influenza A virus subtype, H7N9, is over...for another season anyway. 

If we get into the nitty gritty, as I have below, there are a couple of interesting things to see. First though - let us remember that these are just reported data:

• there may have been some cases that were not reported for whatever political, medical, social or personal reasons - these data are an idea of what happened - look at the rends and don't get hung up on the specific values
• the overwhelming majority of the cases have reported to a healthcare facility with respiratory disease due (presumably) to either infection - we have no idea how many other people have been infected, what proportion were mild or asymptomatic (as I've discussed e.g. here and here, so we know it is possible). It could be half as many again, or 100 or 1,000 times as many.
• these are only cases that have been examined with a laboratory test (as far as we know) - there may have been many other cases of "influenza-like illness" that did not get sampled and tested but were managed under (or not) the assumption that they were influenza of some type, subtype or strain.

Please note-the graphs used here can all be found on my fixed interactive H7N9 page at:http://virologydownunder.blogspot.com.au/2014/11/influenza-ah7n9-virus-detection-numbers.html

The interesting stuff includes:

• For the 2 outbreaks we have continuous data for - 2013-14 and 2014-15, the start of the outbreak seems to be around October/November, with the peak around January/February. 
• Outbreak 3 did not seem to reach the heights of the preceding year however, from what we could glean from pretty poor data, the link to poultry exposure was as strong as ever. Perhaps market closures in response to deaths were a little more effective/efficient/wide-ranging in Outbreak #3? Pure speculation

Click on graphs to enlarge.

• Most of the cases in 2015 (bottom maps) were on the east coast of China

Click on map to enlarge

• Most of the activity in the 3rd outbreak was focussed in Guangdong, Fujian and Zhejiang provinces (the red ones above) 
• Xinjiang Uyghur Autonomous region (in the far west) and Guizhou and Hubei provinces joined the list of host regions in Outbreak #3
• Xinjiang joined Guangxi and Jilin provinces (which reporting cases in Outbreak #2) as regions of China that share a border with another country - heralding the movement of this H7N9 variant beyond China's borders possibly into Vietnam, North Korea, or a -stan

Click on graphs to enlarge.

Keep an eye out for H7N9 Outbreak #4 - coming to a colder China around November 2015. 

But for now, it might be time to hit the FluTrackers line lists (okay, I've had 4 tabs open for ages) and graph the course of another source of concern - H5N1 cases in humans.

Perhaps Bili|1956 was an Ebola virus disease outbreak...

I didn't blog this one earlier in April when it was mentioned in the literature, but have been reminded of it by Secret Squirrel D in relation to my last post.[1]

The main gist of the Letter to Lancet Infectious Diseases by Colebunders and Van den Ende [2] is that there was a clinically compatible outbreak of disease in Bili, Democratic Republic of Congo in 1956 - 20 years earlier than the first documented and laboratory-confirmed EVD outbreak there - when the DRC was called Zaire.

The 5-week disease outbreak manifested as a fever and rash followed after 10 or so days by bleeding from the mouth and nose and some times bloody diarrhoea. Vomiting blood was a precursor to death. Those without any bleeding survived and recovered after 3-weeks.

About 80 of at least 215 people died (37%), with cases clustering among family groups. A very good survival rate for some filovirus infections. Quarantine efforts and safe burials  seemed to halt the outbreak although some bodies were "recovered" by family for re-burial under more traditional circumstances. Its not clear if this process caused any new infections as it did in west Africa in 2014.

The authors of this letter conclude that the disease course, consumption of monkey meat (but not bats, despite the proximity of colonies) suggests the outbreak could have been due to a filovirus of some sort.[1]

Unfortunately we don't know which filovirus, if a filovirus at all, was responsible since there was no laboratory testing to confirm the specific agent. 

So this one remains a "could be" for now. If only there were stored samples.

References...

1. Yes, there were signs that Ebola was in west Africa, perhaps as far back as 1973...
   http://virologydownunder.blogspot.com.au/2015/04/yes-there-were-signs-that-ebola-was-in.html
2. Filovirus epidemic in 1956 in Bili, DRC
   http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(15)70092-7/fulltext

Jeddah changed the MERS-CoV age:sex landscape...

Note. Not every death or case is listed.
See bottom-left corner for breakdown.
Click on charts to enlarge.

I've broken down the age and sex in these charts.

As usual, it's mostly about males and older people until we get to the Jeddah outbreak.

In the top pair of charts (note the different scale used here compared to that used in the charts below) we see the breakdown for all MERS-CoV detections to date on the left and the fatal cases from among those on the right. 
An apple in terms of people shapes.

In the middle pair of charts we look at all cases form 2012 up until the day before the Jeddah outbreak. The total case pyramid shows an older age bulge but the deaths look very similar to those for all fatal outcomes. M:F is similar to the total case charts above.

In the bottom pair of charts we're looking at what happened from the beginning of the Jeddah outbreak until now. We see a marked change in distribution with many more younger adults being positive for MERS-CoV. We also see a major shift towards more females than we'd seen beforehand. All the result of more widespread testing and a greater healthcare worker contribution I presume. Strangely though, given the younger adult demographic here, we see no accompanying jump in numbers of children. Are they not subject to testing? Are the younger adults often foreign workers who do not have children/children with them with them? There is no reason for children to test any less frequently MERS-CoV-positive and they are also just as likely as healthy adults to get mild or asymptomatic disease (as far as we know). If positive, children will have an important potential role in the MERS-CoV transmission story, especially when visiting elderly relatives.

The recent Al Qunfudhah teacher who is MERS-CoV just reinforces that children are shaping up to be a strange data gap. Yeah. I know. Another one.

MERS-CoV cases continue steep climb thanks most to 2 healthcare-related clusters...

Click on image to enlarge.
Data are for lab-confirmed cases only, and 
from FluTrackers, Ministries of Health
and the World Health Organisation Disease Outbreak
News reports.

The Jeddah cluster | Jeddah | Kingdom of Saudi Arabia. 

It is the biggest of any of the clusters of MERS-CoV cases within the Kingdom of Saudi Arabia, MERS-central (0 to date. It has seeded at least 2 internationally exported cases (a fatal case in Malaysia and now a case in Greece). It totals 53 cases so far; the tally for this cluster began after the onset of illness in the first case, 6-Apr.

The paramedic cluster | Abu Dhabi | United Arab Emirates

Happening simultaneously and right next door is a cluster of cases that began 28-Mar. It stands at 14 cases as I compose this; most recent with an onset of 14-Apr.

These dates, starting points and information are all up in the air of course. 

There have been no solid answers from either site on how each cluster commenced, so we don't know the actual 1st case nor how they became infected, what their status is or what type of contact occurred (animal or human-to-human). 

We don't know how many cases are linked together or even whether the 2 sites are linked. We don't know whether these focal outbreaks are ongoing nor just how so many healthcare workers (HCWs) can be infected by a respiratory virus that was already well known to the region and its hospitals (Wk 109, 2.1 years since first MERS cases). 

We don't know if this outbreak is just bad infection prevention and control at some hospitals/among some people. We are all wondering how this has continued among HCWs as it seems to be? After a couple of confirmed cases wouldn't masks and gloves and gowns be standard fare - if they weren't already in the management of unknown acute respiratory disease cases? Whether a "super spreader" is involved or not, such measures should have prevented so many healthcare workers becoming infected shouldn't they? 

Is this MERS-CoV Mk II - now with the ability to transmit efficiently and rapidly (before extra prevention measures are in place)? We have no MERS-CoV sequences to answer that. Spike gene sequences would at least help us understand he virus aspects? I don't really care about complete genomes-they are for phylogeny more so than public health; changes in Spike yielded information of value in the SARS-CoV event and for coronavirus in general, and could do so again. Just sequence that region guys! Do it quickly and release that info now. It's something informative. Don't wait for a scientific paper. Start a blog and put the results on there. Not just in Arabic and then in English some time later; with Yemen, the Philippines, Malaysia and Greece picking up cases in the past week, these 60+ cases are not just a Saudi thing (although the case numbers say otherwise-but you know what I mean), it's global village thing. Just tell us what's going on with the virus! 

So many things we don't know. "So what?" you ask Go and Google "MERS SARS" and limit it to the past 24-hours. That's so what. The media are starting to heavily lean towards the "MERS is the next SARS" story again and that stirs up concern at many levels. Is that concern justified. At the moment who the heck knows??? If there is no change in Spike, while not the be-all and end-all for change in the virus, it will allow the experts to make comments that inform the media that may calm a rapidly progressing situation with economically damaging potential for the world, and the region.

For crying out loud Ministry of Health|Saudi Arabia, get ahead of this thing.

Sources...

1. The world's greatest resource for tracking MERS-CoV cases, the FluTrackers line list
   http://www.flutrackers.com/forum/showthread.php?t=205075

Ebola outbreak in Guinea: 13-lab confirmed cases, 73 more suspect, includes 59 deaths

Schematic of an Ebola virus virion.
Its a work in progress but feel free to use.
Just cite Ian M. Mackay, PhD and
http://virologydownunder.blogspot.com.au/
Click to enlarge.

There's an outbreak of Ebola virus (species Zaire ebolavirus) haemorrhagic fever going on in Guinea just now (see the map for where that is within Africa).

Haemorrhagic fever? That's the scary stuff that books get written about and movies based on - bleeding from tissues and person-to-person spread to infected healthcare workers and grieving family carers...horrible, scary stuff for those in the thick of it. If anything can be said to be good news to this, it is that usually (to date) cases do not pass several hundred (see Storify article of tonight's Twitter information [5]) because the virus does not transmit as easily as influenza for example (no aerosol route; spread is by bodily secretions);  scary bleeding from everywhere is not as common as the movie make out and there are survivors of infection. 

A very digestible backgrounder on Ebola that will get you up to speed on this virus and disease can be found at Mike Coston's Avian Flu Diary, here [9].

On 22-March, the World Health Organization (WHO) was made aware of an outbreak in the west African country by its Ministry of Health [1]. The outbreak of febrile disease commenced 9-Feb. When the Minister of Health released a statement, 22-Mar, he noted the disease was characterized by fever, diarrhoea, vomiting, fatigue and sometimes bleeding. 

Guinea and surrounds, Africa.
Maps purchased from maptorian.
Click on image to enlarge.

Since then, haemorrhagic fever cases in the country's capital, Conakry, have been shown to be due to something other than the Ebola virus according to testing results from the Pasteur Institute Dakar [3]. 

The Institut Pasteur in Lyon had earlier identified Ebola virus (so far in 13 cases) in Guekedou, Macenta, Nzerekore and Kissidougou districts; they also genotyped some strains using the L gene as a PCR target[10]. This led to identifying the species Zaire ebolavirus.

The Emerging and Dangerous Pathogens Laboratory Network (EDPLN) is working with the Guinean VHF Laboratory in Donka, the Institut Pasteur in Lyon, the Institut Pasteur in Dakar, and the Kenema Lassa fever laboratory in Sierra Leone to make available appropriate Filo-virus diagnostic capacity in Guinea and Sierra Leone [1]

There is no specific treatment or vaccine for Ebola disease. The first Ebola virus outbreak was identified in 1976. Ebola virus is the conversational name of the viruses that are members of the Family Filoviridae, Genus Ebolavirus and exist as 5 species [4]:

1. Species: Tai Forest ebolavirus ("Tai Forest virus")
2. Species: Reston ebolavirus ("Reston virus")
3. Species: Sudan ebolavirus ("Sudan virus")
4. Species: Zaire ebolavirus ("Ebola virus")
5. Species: Bundibugyo ebolavirus ("Bundibugyo virus")

"Multidisciplinary teams have been deployed to the field to actively search and manage cases; trace and follow-up contacts; and to sensitize communities on the outbreak prevention and control. Médecins Sans Frontières, Switzerland (MSF-CH) is working in the affected areas and is assisting with establishment of isolation facilities, and also supported transport of the biological samples from suspect cases and contacts to international reference laboratories for urgent testing." [1]

But where was the crack team of experts laden with ultra cool tech capable of diagnosing the tiny beast within minutes, containing it within hours and saving more people from becoming afflicted in days? 

Unfortunately no such crack team or timeline exists, except in the movies anyway. But as we are going to see in the coming days as diagnostic delays cause headaches for those multidisciplinary teams trying to educate the locals and begin helping contain, confirm cases and trace the disease, there is a real need for faster identification of the causes of acute and serious disease outbreaks worldwide. 

Wouldn't it be great if the world's governments and biotech industries could come together to assemble and maintain some sort of rapidly deployable multinational pathogen detection force? Several teams of scientists and healthcare workers assembled and trained by the world's best, and remaining linked to them, carrying with them all the (perhaps bespoke) tech they'd need to identify any pathogen (unbiased molecular methods). They could analyse their data on the fly or rapidly send it to others for help using satellite links. The "Force" could be funded by the contributing States, biotech and Pharma; coordinated by the WHO perhaps. I'd love to see a dedicated set-up for pathogen identification; a kind of virus/bacteria/parasite-hunting fire department that can down its regular tools and jump on a plane ASAP; someone whose number is on every country's speed dial. 

Ahh 'tis to dream. 

In the meantime, I have a lot to learn about Ebola; something that is more nightmare than dream to me.


References..

1. WHO situation report as of 22-Mar-2014 [PDF]
   http://www.afro.who.int/en/clusters-a-programmes/dpc/epidemic-a-pandemic-alert-and-response/outbreak-news/4063-ebola-hemorrhagic-fever-in-guinea.html
2. Epidemic hemorrhagic fever in Guinea after 29 deaths, the Health Minister announces new measures
   http://www.lejourguinee.com/index.php/fr/societe/3072-epidemie-de-fievre-virale-hemorragique-en-guinee-apres-29-morts-le-ministre-de-la-sante-annonce-des-nouvelles-mesures
3. Guinea: fever cases detected in Conakry are not due to Ebola.
   http://www.france24.com/fr/20140324-guinee-conakry-ebola-virus-fievre-hemorragique-epidemie-institut-pasteur/
4. Prof Vincent Racaniello's Virology blog on Ebola virus naming
   http://www.virology.ws/2012/08/07/is-it-ebolavirus-or-ebola-virus/
5. Storify: Early timeline of the events in the Guinea Fever outrbreak
   http://storify.com/MackayIM/early-timeline-of-the-eventsin-the-guinea-fever-ou
6. WHO webpage on the Guinea Ebola outbreak
   http://www.afro.who.int/en/clusters-a-programmes/dpc/epidemic-a-pandemic-alert-and-response/outbreak-news/4063-ebola-hemorrhagic-fever-in-guinea.html
7. WHO primer on Ebola haemorrhagic fever
   http://www.who.int/mediacentre/factsheets/fs103/en/
8. Avian Flu Diary (Mike Coston) on WHO Twitter Messaging On Ebola
   http://afludiary.blogspot.com.au/2014/03/who-twitter-messaging-on-ebola.html
9. Avian Flu Diary (Mike Coston) on A Brief History Of Ebola
   http://afludiary.blogspot.com.au/2014/03/a-brief-history-of-ebola.html
10. Guinea Ebola outbreak believed to be deadly Zaire strain
    http://www.reuters.com/article/2014/03/24/us-guinea-ebola-idUSBREA2L0MI20140324

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

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.

Just normal viruses folks.

It seems that the cluster is a collection of normal respiratory virus infections. Its worth remembering that it is very hard to distinguish between the 200+ different respiratory viruses using signs and symptoms alone. What is usually a common cold virus has been found to trigger asthma attacks and been associated with middle ear infections, pneumonia, bronchitis, influenza-like illness...its a game of probabilities.

Certain viruses are usually cause certain disease. Usually is not always.
In the current climate of MERS-CoV and H7N9 it's understandable that an uptick in acute respiratory illness cases causes alarm but the odds are in favour of one the usual culprits today.

This event is also a reminder of the great job done by expert public disease diagnostic entities like the CDC during times of disease outbreak. Imagine the number of samples that get sent to the CDC for special investigations then scale that up logarithmically during outbreaks. Realistically, even during a pandemic, to find an answer to the type of infectious agent a patient may have requires many separate tests to be conducted on each sample. Time is needed to receive, log and store each patient specimen, to set up, add to and run the diagnostic methods, to carefully interpret the results, sometimes to repeat or add novel testing methods and then to report the results to an increasingly data-hungry public. There's a lot of specialist work in there - even with high throughput system in place these things take some time. We should remember that when reading headlines like "CDC still 'investigating' mystery illness". The implication could be that there is thumb twiddling going because a press releases doesn't appear as quickly as a pirated TV episode on a torrent site. Be assured that there are many steps in a process that seeks to get it right first time.

On a side note, this makes a great case for enhancing diagnostic testing capacity to detect seasonal and endemic respiratory viruses at the local hospital laboratory level. Its surprising how few labs regularly test for the 150+ known rhinoviruses or the 4 non-SARS/MERS coronaviruses for example - together called common cold viruses.

"Mystery" respiratory illness in Alabama, US.

The past couple of days has seen many reports on a growing number of cases of cluster of acute respiratory illness. The Alabama Dept of Public Health (ADPH) issued an alert yesterday requesting that care providers to be on the lookout for unexplained case of pneumonia.

Cases of interest present with fever, cough, shortness of breath and "something" on their chest x-rays. Upper airway swabs or aspirates have been requested from such cases, regardless of "quick flu" test results. To date, samples have been collected and sent to local labs and to the US CDC.

A total of 10 cases - including 2 deaths (30-40y of age ) - are yet to be linked to a suspected pathogen and are not epidemiologically linked to one another.
Two cases positive for influenza (H1N1 and a seasonal H3) have already been reported (rapid antigen point of care testing?) although the flu season is currently winding down in the US. Two patients have already been discharged.

The cluster of respiratory illness can be traced back to around April 19th. Preliminary testing results should be arriving from the CDC soon.

FluTrackers are keeping a close eye on every report here.

The crowded virus escapes from Hofuf?

While MERS-CoV (f. HCoV-EMC) cases have been detected in the UK (3-2 fatal), Jordan (2-both fatal), the United Arab Emirates (1, fatal) and Qatar (2) since April 2012, it has been the Kingdom of Saudi Arabia (22 cases-13 fatal) that is the current hot zone. 

These cases are from 5 different clusters according to the FluTrackers. 

The latest news paints a bleak picture. According to the Wall Street Journal, Al Moosa General Hospital is not the only hospital treating patients from the current outbreak. 

Given that human-to-human transmission has been noted for MERS-CoV, this may nor bode well for containment.

H7N9 outbreak Week 6 begins.

We start week 6 of the H7N9 outbreak with confirmation...or new test results....that H7N9 (not some other H7) is indeed among the poultry in Guangdong province, which is adjacent to Hong Kong. 

One sample was positive from s wholesale market in the city of Dongguan, which had previously (see post on 28.04) been positive for an H7 virus that was not H7N9.

Previous testing of 542 poultry workers (method unknown) in Guangdong had not identified H7N9 infection. As ProMED noted, in "AVIAN INFLUENZA, HUMAN (71): CHINA H7N9 UPDATE", this makes animals sentinels, instead of humans, for H7N9's presence for the first time during this outbreak. 

Shows the benefits of screening for virus without relying on symptomatic presentations hmm?