Sunday, 23 February 2014

Live bird market closures continue...

Changsha, capital of Hunan province has had its live poultry markets closed since 21-Feb (1).
H7N9 case map.

So that can be added to Shanghai, major markets in Hangzhou, Ningbo and Jinhua cities in Zhejiang (15), markets in Guangzhou, Guangdong ((3); plus a previous 2-week pause for disinfection in Shenzen (15) ), Hong Kong recently extended its ban (4) on live poultry imports from mainland China and Fujian provinces markets were closed fro disinfection back in 21-Jan. 

No word, that I can find anyway, on market closures in the Jiangsu province (11.8% of all H7N9 cases), other sites in Fujian province (5.5%) or Anhui province (2.5% but over-represented in cases recently).

And yet with no cases announced yesterday - the latest in a recent precipitous decline in total human cases per day - it's tempting to wonder whether market shutdowns in regions that have had the highest case activity (Zhejiang and Guangdong provinces) and which produce or trade a lot of the nation's chickens, have had enough of a flow-on effect to stem the tide in other regions supplied by these. 

Aside #1: Poultry eggs are mainly produced by >1-billion birds in Henan, Shandong, Hebei, Liaoning, Jiangsu, Sichuan, Hubei, Anhui, Heilongjiang and Jilin (7,8) whereas >4-billion broiler chickens (bred for meat) are more concetrated in Shandong, Jiangsu, Guangxi, Liaoning, Guangdong, Anhui, Sichuan and Henan provinces  (2,6,8,9,10,11,12,13).
Aside #2: An interesting to read (5,9) that the volume of chicken consumed per capita has risen by 9-fold or more in recent years - it has not always been the staple but is part of the tradition.

Sources...


  1. http://english.cri.cn/11354/2014/02/22/2702s814226.htm?utm_source=dlvr.it&utm_medium=twitter
  2. http://www.globaltimes.cn/content/843788.shtml#.Uwl4ovna6-1
  3. http://virologydownunder.blogspot.com.au/2014/01/zhejiang-live-bird-market-closures-and.html
  4. http://www.interaksyon.com/article/81029/hong-kong-extends-ban-on-live-poultry-imports-from-mainland-china
  5. http://www.iatp.org/documents/fair-or-fowl-industrialization-of-poultry-production-in-china
  6. http://www.forbes.com/sites/russellflannery/2013/04/13/by-the-numbers-chinas-poultry-industry/
  7. http://www.prweb.com/releases/chinas-egg-and-poultry/industry-research-2013/prweb11170628.htm
  8. http://www.ccagr.com/content/view/117/184/
  9. http://www.newschinamag.com/magazine/poisoned-plucked-processed
  10. http://www.tysonfoods.com/Around-the-World/International-Operations/Tyson-China/About-Tyson-China.aspx
  11. http://www.wantchinatimes.com/news-subclass-cnt.aspx?cid=1103&MainCatID=11&id=20140219000043
  12. http://articles.chicagotribune.com/2012-04-19/business/sns-rt-us-usa-china-food-factboxbre83j05v-20120419_1_hog-farm-province-hubei
  13. http://english.agri.gov.cn/hottopics/ah/201310/t20131028_20492.htm
  14. http://news.xinhuanet.com/english/photo/2014-01/22/c_133063832_2.htm
  15. http://news.xinhuanet.com/english/china/2014-01/31/c_133087279.htm

H7N9 snapdate: nothing new to report

No new human cases of avian influenza A (H7N9) virus yesterday.

None.

Markets.

Precipitous.

Friday, 21 February 2014

H7N9 appears in a new north eastern Chinese province: Jilin

Click on image to enlarge.
...and the map expands a little more. 

It would be interesting to know if this case was acquired from a live poultry market stocked with birds sourced within the province or from the vast network of poultry movement that links the provinces and their markets across thousands of kilometres.

As I write this, there are 365 cases and 113 deaths, if I can add the latest Guangdong fatality to the 112 I wrote about, earlier today.

H7N9 deaths jump significantly....

Click on image to enlarge.
Twitter was buzzing this morning with news that several sources had announced a new total number of deaths in human cases of H7N9 infection.

It was not a total surprise that there were more deaths than we had heard about, and that is for several reasons:
  • In Wave 1, Spring 2013 in South east China, there had been a greater proportion of deaths than we have seen in Wave 2. That's seemed unusual.
  • After Wave 1, the proportion of fatal cases (PFC; see background here) sat up as high as 33%. Wave 2's high case numbers but few reported deaths had lowered that to 18% at one point. If the virus hadn't changed and human-to-human transmission had not changed then that was incongruous
  • The media were reporting higher numbers than we had data for in early Feb and in late Jan, Xinua reported 26 deaths in Zhejiang alone for 2014 - this far outstripped any publicly data available
So now we see that the tally is 112 fatal H7N9 cases among people infected with a laboratory confirmed H7N9 virus, since the outbreak began in 2013; that tally includes both waves of human cases. That makes the PFC among the 361 confirmed human cases at 31%. 

So this one new piece of news has bumped up the PFC by 10%. From 1:5 (22% last week) to nearly 1:3 cases dying after acquiring infection. 

Thankfully, H7N9 is not spreading efficiently among humans (or chickens according to reports). But these are numbers to care about.

For comparison, my Excel sheet has 64 cases with data that I can cross-check (I believe that agrees with the FluTracker's count also). 

The last media update I looked at had a tally of 77 fatal outcomes

So we have between 35-48 people have died without any ability for anyone outside China to link them to:
  • their age
  • when they became ill
  • where they were
  • how they may have acquired their infection
  • their sex
  • time to hospitalization and diagnosis
  • length of stay in hospital 
  • what contacts they had and how they have fared. 
I think that this is a ball that has been not just been dropped, but buried in a hole and covered over with feathers. I'm disappointed by such a gaping data loss. And don't get me started about the absence of H7N9 sequences from 2014 cases!

Sources...
  1. SCMP with higher death tallies than public data indicated
    http://www.scmp.com/news/china/article/1425289/january-worst-month-chinas-human-h7n9-outbreak
  2. Xinhua lists 26 deaths in Zhejiang alone for 2014
    http://news.xinhuanet.com/english/china/2014-01/21/c_133060657.htm
  3. VDU blog on missing deaths
    http://virologydownunder.blogspot.com.au/search?q=deaths+h7n9
  4. Mike Coston's Aviann Flu Diary take one the new data, with other sources
    http://afludiary.blogspot.fr/2014/02/chinas-moh-h7n9-fatalities-higher-than.html?m=1&utm_source=dlvr.it&utm_medium=twitter
  5. FluTracker's thread with links to eth WHO report
    http://www.flutrackers.com/forum/showthread.php?p=525996#post525996
  6. China's Ministry of Agriculture report of enlarged H7N9 death tally
    http://translate.google.com/translate?u=http%3A%2F%2Fwww.moa.gov.cn%2Fgovpublic%2FSYJ%2F201402%2Ft20140220_3791429.htm&hl=en&langpair=auto|en&tbb=1&ie=UTF-8
  7. The WHO report under the "vaccines" section
    http://www.who.int/influenza/vaccines/virus/recommendations/201402_recommendation.pdf?ua=1

H7N9 snapdate: epidemic curve as Wave 2 looks to be ending...

Click on image to enlarge.
This image is another way of showing that the current wave of human cases of avian influenza A(H7N9) virus is ending and that we are solidly within a period of "tailing" (cases only ticking over at low levels in the lead-in or lead-out of the main peak).

BUT: These data are based on figures that are publicly available. As we learned overnight, those numbers can come in fits and starts, if at all. The addition of a large number of deaths without any identifying information linking to the case onset, supports what some have been suspecting for a while; we don't have a full picture of what's happening with H7N9. 

There are now up to 48 more deaths due to H7N9 infections, depending on where your base count is taken from (verified updates or or the media) than we knew about 12-hours ago.

More on that topic later today.

Thursday, 20 February 2014

Allergy and viral infection: wheeze and more wheeze

I really liked this Letter by Karta and colleagues from the University of Wisconsin. Not just because it makes some sense to me but because it's not a long drawn-out immunology study written in alphabet soup with multiple 12-panel figures that make me cry.

Trying to understand how viruses (my thing) trigger asthma exacerbations (a clinical thing) via activation of multiple inflammatory pathways (an immunology thing designed to be impossible to follow unless you love keeping tract of tiny little initialisms and what each of them do, did and used to be called 5-minutes ago) is heavy going. This Letter somehow adds to the field without all of "that".

The authors obtained mononuclear cells from the lower respiratory tract of 10 volunteers with mild atopic (allergic) asthma, by bronchoalveolar lavage. That was Day zero (D0). At 48-hours (D2) the donors were given an allergen and cells were collected by BAL again. 

Macrophages were obtained from the D0 and D2 cells (they stick to the plastic culture flasks, other blood cells don't) and they were then challenged with 1 of 3 rhinoviruses (RV); either RV-A16, RV-B14 or RV-A2. I say challenged because rhinovirus doesn't replicate within macrophages (also written in shorthand as MΦ) but they do interact with them.

The team then looked at a bunch of initialisms which represent some potent chemicals called chemokines:


  • CXCL10 (IP-10)
    • C-X-C motif chemokine 10; formerly interferon gamma-induced protein 10
    • secreted by macrophages that have been activated by RV interaction
    • also secreted by endothelial cells and fibroblasts
    • secreted from cells in response to interferon gamma (IFN-γ)
    • signal the recruitment of immune cells  (monocytes/macrophages, T cells, natural killer [NK] cells and dendritic cells) that take charge of getting rid of virus
  • CXCL11
    • C-X-C motif chemokine 11; formerly known as Interferon-inducible T-cell alpha chemoattractant (I-TAC) and Interferon-gamma-inducible protein 9 (IP-9)
    • also secreted by macrophages that have been activated by RV interaction
    • secreted in the pancreas and liver
    • secreted from cells in response to IFN-γ and IFN-β
    • interacts with cell surface receptor, CXCR3
    • recruits activated T-cells
  • CCL2 
    • Chemokine ligand 2; formerly known as monocyte chemotactic protein-1 (MCP-1) or small inducible cytokine A2
    • can also be secreted by macrophages after RV exposure
    • also secreted by monocytes and dendritic cells and expressed by neurons, astrocytes and microglia
    • recruits monocytes and basophils
    • binds to the cell surface receptors CCR2 and CCR4
  • CCL8
    • Chemokine ligand 2; formerly known as monocyte chemoattractant protein-2 (MCP-2) 
    • can be secreted by macrophages after RV exposure
    • recruits mast cells, eosinophils, basophils, monocytes, T-cells and NK cells
    • binds to cell surface receptors CCR1, CCR2B and CCR5
Some key findings...
  • D2 samples that were not challenged with virus made less CXCL10, more CCL2 and nothing much changed in levels of CXCL11 or CCL8.
  • D0 samples incubated with RV saw a statistically significant rise in the amount of all 4 chemokines
  • D2 samples incubated with RV saw a rise in CCL2 but a drop in CXCL10 and CXCL11 but no effect on CCL8 
So the first batch of findings indicate that RV infection does not induce the same chemokine response from lower airway macrophages of people with allergy that have just been exposed to an allergen (think pollen or dust mite).

Further, it identified that in macrophages, a key immune cell in controlling viral infections in the airways, may not respond as effectively to RV infection in the body if such infection follows an allergen hit. At the same time, increasing CCL2 may increase inflammation by attracting those types of cells (eosinophils, neutrophils and more macrophages).

The team also went on to look at the levels of the 2 known RV cellular receptors, intercellular adhesion molecule I (ICAM-1) and the low density lipoprotein receptor (LDLR) and LDLR-related protein-1 (LRP-1). Receptors have been used as a way to categorise RVs in the past and some adhere to this when making choices in the design of their immunology research relating to RVs.
  • D2 macrophgaes had raised levels of ICAM-1 on the cellular surface but lowered levels of LDLR and LRP-1
  • Other blood cells showed no difference in receptor levels
  • Allergen-induced effects on RV receptor expression are distinct from its effects on chemokine levels
Great to know that RVs are ubiquitous and so are allergens!

References...
  1. Information on some cytokines and cell signalling following viral infection
    http://www.jleukbio.org/content/74/3/331.full.pdf+html
  2. Wikipedia as a starter for detail on cytokines

Wheezing after respiratory virus infection...

Takeyama and colleagues from Japan delved into the viruses present among young children (≤ 3-years of age) hospitalized with a clinically defined lower respiratory tract infection.

This exemplifies what many such studies do; sample from the upper respiratory tract to find signs of replicating virus in order to study a disease of the lower respiratory tract

It's a stretch but if you go along with it you are implying that an upper respiratory tract infection either triggers the symptoms from afar or that the virus travels into the lower respiratory tract to directly cause inflammation and/or cell destruction.

Viruses were detected by PCR-based methods.

Some key findings...
  • Respiratory syncytial virus (RSV) was the virus detected most often (51/102 samples from 153 children) in children who were admitted with wheezing followed by rhinoviruses (RV; 21 or 14%), RSV+RV (12 or 8%) and then parainfluenza virus 3 (PIV3; 8 or 5%), influenza virus (IFV; 5 or 3%) or human metapneumovirus (hMPV; 5 or 3%)
  • A similar pattern was observed in 259 children who were admitted without wheezing (RSV-25%; RV 9%; IFV 7%; RSV+RV-4%; PIV3-3%; hMPV-1%)
  • 67% of children with wheezing were virus positive (POS)
  • Children with an allergic predisposition (IgE antibody levels >30IU/mL at admission and a parental history of asthma) POS for RSV more often had wheezing later
  • Children who were wheezing & RV POS when they were admitted were more likely to wheeze again than were those who were RV POS without wheeze at admission.
So [allergic predisposition + RSV] or [wheeze/clinical severity + RV] were 2 factors related to subsequent wheeze.

The authors also raised the spectre of RV positivity occurring in asymptomatic individuals in other studies. However, that can happen to some extent with all respiratory viruses. No other virus has 160 distinct type like the RVs...but that's another story.

Article...

Humans unlikely to infect poultry with H7N9? Data please!

The United Nations Food and Agriculture Organization (FAO) has said that poultry is not at risk of being infected by humans carrying H7N9 virus.
In fact, we have no evidence that affected people could transmit the virus to other species, including birds. The highest risk of virus introduction is uncontrolled live poultry trade between affected and unaffected areas.
But absence of evidence is not evidence of absence.

We have seen studies, like this one, that use a human H7N9 virus and use it to successfully infect chickens. So the virus is capable of replicating even if it is inefficient at spreading to other chickens or even ferrets ( a human surrogate of influenza infection). But then we do know that humans get infected from exposure to something in poultry markets.

I agree (for what that's worth), that the risk of spreading virus is more in the area of moving infected birds around, as well as their own migration movements. But I think it is too early be early to issue strong denials that humans may infect poultry until we find some data to support them.

Sources...

Why I think the 2nd wave of human influenza A(H7N9) virus infections has broken...


If you look at the chart above, it shows declining:

  • Average cases per day (blue data points) in 2014
  • Less noticeable but consistently declining average cases per day when calculated across all of Wave 2 (oranges data points)
  • And importantly, a drastic decline in the number of new cases being announced after the 27-Jan peak. 

From 5-Feb, we have not seen more than 2 cases/day whereas in Jan we were regularly seeing 5-6 cases/day (peaking at 12/day).

The last time we saw this steep a drop in cases was 19-Apr 2014; the end of H7N9's 1st wave of human infections. 


That doesn't mean the virus has gone away or that the outbreak has been "solved". I learned that lesson last year. H7N9 is still out there. 


If these latest case numbers accurately reflect what is happening in China, then it looks like closing poultry markets did the same job in 2014 that it did in halting the 2013 Spring outbreak in southeast China. It will be down to the poultry industry and perhaps the Ministry of Agriculture in China to find evidence that specifically disproves a role for poultry in human infections; and it seem clear that changing from fresh to processed poultry has some even more safety data to support it.

We still have no data that lets us point the finger at chickens, or ducks or song birds or pigeons or geese or some other animal in the markets as the source. 

We just know there is a strong association between humans getting infected after being in the presence of "live poultry" usually in a market setting. With reports suggesting better growth of H7N9 in song birds compared to chickens as well as poor spread of virus between infected chickens, there is much work to be done outside of chickens to track the source of the virus down.


Wednesday, 19 February 2014

I care what the H7N9 numbers are...


This was the Tweet from Crawford Kilian (hereafter "Crof") a couple of days ago. 

I respect Crof. He has been as much of a mentor in my year doing this as has anyone. He even sent me his book on "Writing for the Web". I immediately changed a few things that I did after reading parts of it. Unfortunately nothing can help my appalling typing skills.

So when I saw that Tweet I thought it must have been a hook to get people to come read the full story. Twitter is a great way to attract readers to my blog; its a top referring site. Among other things, it's an important tool for promoting what we write to a wider audience. Sometimes a catchy title can be as good a bait as something more straight down the line. So, hooked, I dutifully read on.

What I found has been disappointing me ever since I read it 2 days ago, because I care about these numbers, and I thought you did too, Crof.

The article is of a type that I have read several times from Crof. It reminds those of us getting carried away with small, confined disease outbreak that hey, it's a great big world of misery out there and many more people are suffering and dying of all manner of diseases, a lot of which we forget about. Sometimes we don't forget though, we just focus on other things for a time.

I think it is a very valid point to make; and to make it over and over again is also fine with me. Points made in a blog post are very quickly forgotten, if they are ever read in the first place. At least a search engine may lead some back to that post or online newspaper story, unlike a printed newspaper which if not read may never have existed.

What really disappointed me I think...and I've been trying to work out why this has stuck with me for 2-days now, even causing me to give up on writing this last night or on blogging about viruses at all...is that Crof's post never did back away from the message of that original Tweet. Who cares about those numbers? It continued to hammer home that to follow such small numbers of deaths needed a special kind of justification, even for Crof. He said....
When I see WHO's H7N9 updates extending to 10 or 15 cases, it looks a bit alarming, I grant you. But let's put it in proportion.
and
Yes, I pay more attention to avian flu than to lung cancer and malaria. So, unfortunately, does everyone else...if you define "everyone else" as affluent, educated, vaccinated individuals living in countries with excellent public health systems and drinkable tap water.
and 
For us, it's the implicit threat of some clever virus that holds our attention: we don't have a vaccine for this one, so we ourselves are as vulnerable as some kid in Cité Soleil or Asunción or Gorakhpur.
and
I suppose we can justify our interest by arguing that by studying these new diseases, we learn more about other diseases, and ourselves, as well. And that's a plausible argument.

Finishing with
Meanwhile, since I posted a few minutes ago that 768 mothers died in childbirth today, the number has risen to 775.

So Crof, are there so few people on the planet that some cannot keep an eye on one disease, some on another? I get that we do have to prioritise certain diseases over others. We have limited resources and human nature seems such that we never get everyone to pull in the same direction for long enough to truly solve our problems. But there is no definition of a suitably attention-worthy number of lives lost to infection. Every infection that takes a life, or even those that make life miserable, are worthy of our attention, our study, our understanding and eventually, our efforts in defeating it. I care about those numbers.

You cited a number of examples of other causes of far greater human death and disease. I remember a post or comment of yours with similar information that has always sat in the back of my mind as a check and balance of over-reacting.  Yet I have also read many other posts from you that champion the need for better information about MERS and MERS-CoV cases, for example. You often provide "granular" (my word of the month) detail on individuals with infections. You followed the story of a single French MERS patient for many weeks. And so did we because of you. So I simply don't "get" how this post fits, if not to remind us that ALL the numbers are always worthy of our care. 

Yes. There are very few cases of H7N9 compared to the world’s population. But there could be many more, as I know you are more aware than many, with only a few bits of bad luck and circumstance lying between "sporadic" and "sustained". Why not have more eyes rather than fewer on such risks?

There were very few cases of SARS, H5N1 or even now, few new cases of polio or measles compared to such a huge denominator. But each and every one of those diseases has been and should be watched, followed, tracked and its every aspect quantified. 

Every death that could be prevented now with vaccination or in the future by better education, better research, better understanding of the patterns and changes to those patterns, and better awareness by the public themselves, is one more person who remains a living family member. I don't dwell on every death I've reported but I know what it would be like if it happened to someone close to me.  


So I leave you with these 2 thoughts...

And if a little pandemic porn helps all of us protect our health, and outgrow the need for such porn, then maybe it's worthwhile.
..the attention we pay to these fringe viruses is certainly worth the effort..

...and I hope to read many more like them in the future Crof. 

Just like you care about the words that you masterfully write, I think you like me, also really do care about what the H7N9 number are.