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Showing posts with label Guangdong province. Show all posts
Showing posts with label Guangdong province. Show all posts

Guangdong sees sense among the feathers...

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Guangdong province in southern China is suspending its poultry markets. All of them. From 15-Feb to 28-Feb.[1] While the closures are only for 2-weeks, this will be very important for stopping human cases of avian influenza, particularity of the H7N9 subtype, during the bustling spring period in China. 

Live poultry market closures also remove a traditional dish of fresh cooked chicken. One can be certain that no-one will die because of the substitution of frozen or factory prepared chicken for a fresh chicken, even if chefs don't succumb to the tantrums of last year and refuse to prepare dishes made from anything but fresh market-selected poultry. One can be equally certain that if the markets remain operating during the peak season for influenza virus circulation as they have been, that human infections, and deaths, due to H7N9 infections, will also continue 


Guangdong province has been a major
source of human H7N9 cases in 2015.
Some restrictions were put in place back in December 2014 [2], but that did not stop human cases of infection or deaths.

Why does this closure in Guangdong matter? 

Guangdong province has been a major source of human H7N9 cases this year, as it was in 2014. If we look at the activity under the outbreak curves, we can see the brown line of Guangdong cases has been prominent in both years, only brought under control last year after the closure of the poultry markets...although their temporary closure may have been the reason for the long tail on Outbreak #2's epidemic curve compared to Outbreak #1. Will that tailing happen again in 2015 because Guangdong's markets are only being closed for a short period? Time will tell. 

Occurring at a similar time is the change in seasons. Seasonal change towards summer, makes the survival of influenza viruses in the environment more difficult. It's hard to tease out any one main cause of the precipitous case decline; the market closures or the seasons changing or both. Because most H7N9 human cases have exposure to poultry listed among their details when they are passed along and posted by the World Health Organization, live poultry markets clearly are one major factor for human acquisition of infection. There is literature that agrees.[3,4,5]


The activity under the epidemic curves for each of the three outbreaks. Guangdong province-acquired human cases are indicated by the brown line and features in 2014 and 2015.
Having these markets close is a great achievement for stopping these unnecessary and preventable infections and deaths die to H7N9. Its a big step, a sacrifice and its social change in action. But shutting them permanently would be better.

References...

  1. http://news.xinhuanet.com/english/china/2014-02/15/c_126138118.htm
  2. http://www.thepoultrysite.com/poultrynews/33938/guangdong-restricts-poultry-markets-over-bird-flu-fears
  3. http://www.ncbi.nlm.nih.gov/pubmed/25340354
  4. http://wwwnc.cdc.gov/eid/article/20/12/14-0765_article
  5. http://jvi.asm.org/content/88/6/3423.long
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H7N9: the dotted lines that make sense of things...[CORRECTED]

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Click on image to enlarge.
The latest H7N9 case-per-day chart shows that the trickle of human cases of confirmed avian influenza A(H7N9) virus infection is becoming a drip. The tap? My money is still mostly with the market closures. What precisely in the markets is the source of human H7N9 acquisition? Dunno, but the consensus seems to be poultry; songbirds also look pretty good though. It doesn't have to be, and is unlikely to be, just 1 thing of course. We know that this virus, as with other avian influenza viruses, can be shared around among bird species. It can even go into a human and that isolate be used to infect a bird again. See my recent post on some of this.


Click on image to enlarge.
What's also particularly intriguing, among the many interesting aspects of H7N9's acquisition and spread among humans, is that we're seeing much more "shouldering" in the Wave 2 epidemic curve than we did in Wave 1's.

Instead of the precipitous decline we saw back in 2013, we're seeing a drop down to ~10 cases per day, but then a slower decline the rest of the way. Is this because we started human cases from more sites this time around?; because markets took longer to close after the cases numbers began to climb?; is it related to markets being closed at different times, in different ways, in different locales? Who knows?
Cases by region acquired, per week, with different
 regions highlighted by coloured lines and the 
total case number in the background (grey).
Wave 1 and Wave 2.Click on image to enlarge.

Dr Katherine Arden suggested I have a look at what's happening in each Province or Municipality and see whether any particular place can shoulder the blame for the shouldering. And that does seem to be the case if you look at the adjacent chart. Guangdong province seems to be the major culprit contributing to the shoulder effect. 


Cases by region acquired, per week, with different
 regions highlighted by coloured lines and the
total case number in the background (grey).
Wave 2 only.
Click on image to enlarge.
In the zoomed-in version that focusses on Wave 2 alone, we can see that the Wave 2 "peak" has in fact 2 peaks; the 1st peak dominated by Zhejiang province cases and the 2nd driven by a surge in Guangdong provincial cases. Guangdong cases took longer to drop away, and are in fact still being reported, possibly because the major poultry markets there were closed later than in Shanghai and Zhejiang province and only temporarily for a clean. Or perhaps the bird outbreak @influenza_bio and I discussed has a source in Guangdong province?

It's all speculation beyond the data we can actually plot.
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Guangzhou reopens live poultry markets: Good idea or too soon?

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Curve of H7N9 human cases in the two most hard-hit
Provinces in China Zhejiang and Guangdong.
Hangzhou shut its poultry markets 24-Jan.  Guangzhou shut
its markets 15-Feb. Similar rate of cases in Wave 2 of H7N9.
The difference? Zhejiang's markets remain closed.
Well, that seemed like a very quick 2-weeks. But it is 2-weeks (see my earlier post when the markets shut) and a lot of financial hardship for the local poultry industry. They will breath a sigh of relief as the chickens start moving through the crowded markets once more.
With new H7N9 human case announcements reduced to zero for the past 2 nights (my time), we'll now get a look at what happens when a market gets restocked after the region it serviced has had a transmission interruption, and the weather moves towards Spring and its subtropical rainy season. Will the market be restocked from virus-positive farms? Is the weather still conducive to maximising H7N9's chances of being picked up by humans? Will surveillance methods have changed at the markets in Guangzhou? 
"..poultry traders are required to clean their stalls every day, carry out a thorough sterilization once a week and close business one day a month."                                                                                   Shanghai Daily.
It is like watching an experiment played out in real-time. Without the Aims. Or hypotheses. Or controls. Or stuff.

h/t to @Potrblog as my source for this article.

Related links...
  1. Zhejiang province leads the way in H7N9 cases and their decline 3-weeks after market closures...
    http://newsmedicalnet.blogspot.com.au/2014/02/zhejiang-province-leads-way-in-case.html
  2. Guangzhou reopens live poultry markets
    3. http://www.shanghaidaily.com/national/Guangzhou-reopens-live-poultry-markets/shdaily.shtml
  3. China.today Guangdong Province weather
  4. Shenzen shopper weather
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H7N9 snapdate: accumulating cases by region of acquisition

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Click on image to enlarge.
This is what happens when you do nothing to stem the possible source of an influenza outbreak in your back yard. 

Nothing. Nothing changes.

The infection keeps spreading. 

Very clearly the H7N9 hotzone in China has now shifted from Zhejiang province to Guangdong province (the brown line that represent the second highest number of human cases of disease..75 cases representing 21.3% of all H7N9 cases.

As we read today, this province has just shut some of its poultry markets. By the look of this rate of new cases, the people of Guangdong province could be in for a tough 2-3 weeks and will be hearing a lot more about "bird flu" much to the poultry industry's disgust.
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H7N9 snapdate: Zhejiang in the East, Guangdong in the South

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Click on image to enlarge.
Zhejiang province is still climbing in eastern China despite market closures almost 2-weeks ago. 

Guangdong in the south surpasses 50 cases as well as Shanghai municipality and Jiangsu province, in terms of total counts.

Fujian province adds a few cases (at least some markets have been closed for disinfection) and now Hunan province is rising above the background "noise".

CIDRAP recently noted that United Nations Food and Agriculture Organization (FAO) was confident that Vietnam, on the border with Guangxi province (now at 3 cases), had not detected any "signs" (ill people, PCR positive birds..?) of H7N9 to date but intimated porous borders were a reality. And in China, market closures do not necessarily mean a halt to the purchase and household preparation of live/freshly killed poultry; they just necessitate a longer trip into the countryside to maintain spring festival meal traditions.
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From birds to humans....

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Reports indicate 2 new cases of human infection with influenza A H7N9 in Guangdong. The 47-year-old (Foshan) and 71-year-old (Yangjiang) males are both hospitalized and in bad condition.

It was only a matter of time since the market testing has been revealing signs of H7N9 circulating.

For 47M...
"The Guangdong health authorities have on patients 60 close contacts under medical surveillance, not currently found exception."

For 71M...
"The Guangdong health authorities have on patients 65 close contacts under medical surveillance, not currently found exception."

So the contacts are under surveillance but I strongly suspect that if that surveillance was to extend to actual RT-PCR testing, then we would likely see some detections amongst those cases. Symptoms alone do not the full story tell.

My source was Twitter via @pandemic_news and associated blog post here.
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H9N2 confirmed in 86-year old Hong Kong citizen living in Guangdong province...

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Influenza A(H9N2) virus, another "bird flu" but this usually causing mild signs and symptoms of infection, has been confirmed in an 86-year old man reported Dec-30.

The man's underlying illnesses were added to by chills and productive cough from 28-Dec when he was admitted to hospital with a fever.

Sputum tested positive for H9N2. Not sure if an upper respiratory sample was tested.

He had no recent contact with poultry and no contacts have shown signs of illness.

Mild human cases in Hong Kong have previously been reported in 1999, 2003 and 2007 and imported cases in 2008 and 2009.

As ProMED moderator CP (Craig R. Pringle) noted, enhanced surveillance in the region is likely to continue to pick up all sorts of H and N viruses and variants. Interesting watching these pop up - especially if they remain as mild infections, unlike H7N9 has so far.

Sources...

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No symptoms but still shedding virus?

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Click on image to enlarge.
A stylized trace of the temperatures during a PCR cycle.
D-denaturation, when primers and double-stranded
DNA (dsDNA) are reverted to single strands of DNA;
A-annealing, when primers bind to their complementary
target and DNA re anneals to form dsDNA; E-extension,
when the DNA-dependent DNA polymerase enzyme
finds a primer, binds to it attached to a strand of
template  and makes the complementary strand.
Feel free to use. Please cite this website and
Dr I M Mackay as illustrator.
One of the many questions that remain unresolved for MERS-CoV is whether a human who is PCR-positive for the virus, but does not show signs or symptoms of being sick, can spread that infection on to other humans - or animals for that matter.

Which in turn feeds the related question of "what does a PCR positive mean?"

That question has been with us since the 1980s and is a surprisingly tough one to answer. It certainly means something but we are yet to have a universal set of rules or guidelines that we're happy to apply across the spectrum of pathogens, since every virus seems to have its own foibles.

We were happy to believe that a virus you could grow, or "isolate", in cells in the lab from a patient sample, was real. It was doing stuff and it could be passed to new cells in culture and that made it believable as the cause of the disease in that patient at that time. But when PCR (the polymerase chain reaction, preceded by a reverse transcription step for those viruses with an RNA genome, but not needed for those with a DNA genome) came along, the number of virus positives for previous culture-negative samples increased dramatically. This was due to:
  • Inability to isolate some viruses using the cells of the day
  • Viruses present in very small amounts could not be grown by poorly sensitive cell culture
  • Culture was just not reproducible enough
  • Samples weren't transported carefully enough to keep virus alive for culture
The length of time a person is positive for a virus has also appeared to increase using PCR methods leading some to shout "persistence" or "chronic shedding" where really, we are just better able to see what's happening thanks to our new molecular reading-glasses.


Click on image to enlarge.
Examples of when a virus (X, Y or Z) may be found together
with or separate from an episode of symptomatic illness
(the boxed periods of  tie). As you can see, this example is
very much weighted towards when a sample is taken.
3 testing scenarios are shown. (a) 1 sample at the beginning 
and end of a study, (b) sampling only at the beginning of the 
symptomatic periods and (c) regular sampling1. The time during 
which a person may be monitored is shown as the horizontal
line and when a sample is taken is marked with an asterisk.
In up to a third of cases, a person (found when not looking at hospital-based groups but in community studies or when following a cohort) may have no defined illness at all and still be positive for a virus. Heresy!!

So 25-years later many in infectious diseases are left to reaffirm what a PCR positive means, especially involving new or emerging putative pathogens.

For the Middle East respiratory syndrome coronavirus (MERS-CoV) we may be able to draw some conclusions from a viral relative; the severe acute respiratory syndrome (SARS) CoV, did during its short time in humans back in 2002-2003.

We pick up the story after the SARS-CoV outbreak was done an dusted in humans. Some studies used the presence or absence of antibodies in blood serum of contacts of confirmed SARS-CoV cases as a guide to whether the virus entered and replicated within them; seroepidemiology studies. The contacts do not appear to have been screened using RT-PCR; also the current situation with MERS. 

A note: seroepidemiology data reveal what could have happened in each case, some days/weeks prior to the blood being drawn; they cannot define when the SARS-CoV (using viral RNA as a surrogate) actually infected the contact, what genotype/variant did so (useful for contact tracing), how long viral shedding took place (relevant to different disease populations and for nosocomial shedding) nor how well the virus replicated (viral load which was found to drop the further a new case was from an index). 

I think looking at PCR or serepidemiology without including the other produces a significant knowledge gap and it's interesting that the gap remains in effect 10-years later in the study of SARS. Perhaps MERS-CoV is just like SARS-CoV and, as we see below, no symptoms=no infection=no onward transmission. Gut feelings don't really tick the box in science though.

Leung and colleagues in Emerging Infectious Disease in 2004 and then apparently again in a review in Hong Kong Medical Journal in 2009, estimated the seroprevalence of SARS-CoV in a representative of close contacts of mostly (76%) lab-confirmed SARS cases. 

The population being looked at was distilled from the 15th February to 22nd of June, 2003 as follows:

  • 3612 close contacts of  samples 
  • 505 were diagnosed with SARS
  • Of the remaining 3107, 2337 were contacted and 1776 were interviewed
  • 1068 blood samples were analysed for SARS-CoV IgG antibody
Only 2 of the 1068 (0.19%) had an antibody titre of 1:25 to 1:50. Most recovered SARS cases had titres of =1:100. Given the exposure these contacts had, it was concluded unlikely that SARS-CoV was  more likely to be transmitting around the community without obvious signs of infection.

Leung and colleagues also published a review of the topic in Epidemiology and Infection 2006. They concluded an overall SARS-CoV seroprevalence of 0.1% overall with 0.23% in healthcare workers and contacts and 0.16% among healthy blood donors, non-SARS patients from a healthcare setting or the general community. Other interesting bits of information from this review include:
  • 16 studies were examined
  • Asymptomatic infection was <3%, excepting wild animal handlers and market workers
  • In live bird markets, 15% of workers had prior exposure to SARS-CoV (or closely related virus) without significant signs and symptoms
  • In handlers of masked palm civets (older males compared to control groups) in Guangdong, where SARS began, Yu and colleagues reported that 73% (16/22) had SARS-CoV-like antibodies (unvalidated assay) but none reported SARS or atypical pneumonia. Which leaves room for milder illness, and larger studies.
  • Prevailing SARS-CoV strains almost always led to symptomatic illness

So what has been done for MERS-CoV? We have some camel seroepidemiology studies which I've previously described here and here. Human studies?

  1. In the study that found MERS-CoV-like neutralizing antibodies in Egyptian camels, no human sera from Egypt (815 from 2012-13 as part of an influenza-like illness study in Cairo and the Nile delta region) nor any from China (528 archived samples from Hong Kong) were MERS-CoV neutralizing-antibody positive.
  2. No sera or plasma from 158 children admitted to hospital with lower respiratory tract disease or healthy adult blood donors were MERS-CoV neutralizing-antibody positive. Small sample and the ill children may not yet have mounted a relevant antibody response if they had been infected by MERS-CoV.

Work like that mentioned for SARS largely remains to be done for MERS. The SARS-CoV studies provide a useful model on which to base such studies and the World Health Organisation recently provided a detailed approach for seroepidemiology studies seeking to test contacts of laboratory confirmed MERS-CoV cases. 

What does a positive PCR result mean in an asymptomatic MERS-CoV case? Still can't answer that. Are contacts seroconverting as an indication of MERS-CoV infection? Still can't answer that. How many mild or asymptomatic MERS-CoV infections are there beyond contacts of lab-confirmed cases? Still can't answer that.

Once we can rule out occult community transmission - we can tick another concern off the MERS-list.

Further reading...

  1. Observational Research in Childhood Infectious Diseases (ORChID): a dynamic birth cohort study
    http://bmjopen.bmj.com/cgi/pmidlookup?view=long&pmid=23117571
  2. Middle East respiratory syndrome coronavirus: quantification of the extent of the epidemic, surveillance biases, and transmissibility
    http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(13)70304-
    9/abstract
  3. Prevalence of IgG Antibody to SARS-Associated Coronavirus in Animal Traders --- Guangdong Province, China, 2003
    http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5241a2.htm
  5. Viral Load Distribution in
  6. SARS Outbreak
    7. http://wwwnc.cdc.gov/eid/article/11/12/pdfs/04-0949.pdf
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Human H7N9 case in Guangdong province: Update [Updated!]

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Hat tip to crofblogs for alerting me to this news article.

The Guangdong case was confirmed by Chinese CDCP.

A story on Xinhuanet describes that most (54/96) of the contacts of the 51-year old positive woman have been released - it is not clear whether they were lab tested or only under observation for signs or symptoms of respiratory disease. The patients son had a mild fever (now
resolved), but has so far tested negative for H7N9.

I wonder if the child was positive for any other virus, or if H7N9 is/was just not at sufficient viral load yet in the site of sampling (upper/lower respiratory tract).

The consulting clinician who devised the treatment plan, Prof  Zhong Nanshan noted that the current practice is to use twice the amount of Tamiflu with intravenous peramivir to be used sparingly if warranted.

Samples from 69 chickens, 8 ducks, a goose (no partridges?) and 25 environmental samples - all collected from the marketplace where the woman worked - tested negative of any H7-type influenza A viruses.

The mother remains in critical condition.

The H7N9 tally now stands at 136 cases (which includes an asymptomatic boy and Taiwan case not added to the mainland tally) with 44 (according to the Xinhuanet report) deaths. This makes the proportion of fatal case (PFC) is at 32.3%; rising by 1 from the last WHO H7N9 update here [New update just out confirms 44, will be on this list soon).
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