Influenza in Queensland, Australia: 1-Jan (Week 1) to 8-June (Week 23)

Map of Queensland's Hospital and Health service 

areas. Adapted from

http://www.health.qld.gov.au/maps/hhs_facilities.pdf.

Click on image to enlarge.

Waaaay back on 18-March we looked at how influenza notifications in Queensland (population ~5mill) were above the 5-year-to-date (YTD) average. 

"Woopty Doo" some, perhaps very few, of you said. "That number means nothing until you look back at it later". 

So, let's look back at it now that it's later. 

It was Autumn then and now its Winter which is Flu season and also the season when we get some more public info on a handful of other  respiratory viruses circulating here in Queensland thanks to the collatory (I don't care if a dictionary doesn't recognize it) genius of the crew at the State of Queensland, Queensland Health (SoQ|QH).

So what's happening with flu Down Under? For all the detailed detail, I recommend you check out the Open Access document, Statewide Weekly Influenza Surveillance Report that spans up to Week-23 (that's the week ending 8-June; we're in Week 25 now)

Turns out its still 2x (well,  1.987x but who;/s counting?) above the 5-year-to-date mean. No, this is not a "I told you so" - just that it's interesting to see that on this occasion at least, autumn trends predicted a winter event. Still, its only early winter. We've also had a very warm and dry autumn (see the Bureau of Meteorology for more on Autumn) for those who like to link weather and influenza activity.

I like to look at virus interactions as driving their own seasons. How is that possible I eerily hear you ask (I'm not listening to the "Oh what a load of..." comments by  the way, so sit back down and put up your hand)? Well, they don't do anything themselves of course, but my theory goes like this...

When there are enough of us in the community infected by one virus (say respiratory syncytial virus [RSV]) and our immune-thing-a-me-whats-it is all fired up and producing an inflammatory response to rid us off said pestilence, that responsey thing offers a kind of "Shield's Up" effect. 

For a short while we feel like rubbish but we also don't let other viruses get in as easily because we're in an "antiviral state". Enough of us in that state and we get a kind of short-term herd immunity (a fairy died) - where the number of people fully susceptible to another virus (say, an influenza virus) is too small for it to get a good toehold in us and the population. This pattern among seasonal respiratory viruses is most often observed, in my experience, for viruses with an RNA genome like RSV, rhinoviruses and influenza viruses. 

Thankfully for my hypothesis, the data from SoQ|QH show a nice example of this pattern of viruses interacting with viruses within us, projected to the level of the community. 

A snippet from the State of Queensland, Queensland 

Health Statewide Weekly Influenza Surveillance 

Report  for 1-January-2014 to 8-June-2014.
Edited by Ian M Mackay, VDU.

Click to enlarge. 

Let's have a look at the adjacent figure I've mixed around from reference [1]. Hopefully I haven't broken any copyright laws in hacking pasting as I have.

Part A shows the notifications for influenza viruses in Queensland. Peaks and troughs, As and Bs. Cool

Part B shows some of the respiratory viruses, including RSV which has been having a bonza season this past autumn by the looks of things.

Can you see the pattern?

Part C is a cobbled together composite I made in Photoshop/Illustrator by laying B over A and making B partly transparent. It's a bit rough and has had the axis labels and legend trimmed off for clarity, but it makes the point. What it shows (to me anyway) is that when RSV numbers go up, influenza virus notifications head downwards. 

Is this due to RSV influencing influenza or influenza exerting its muscle on RSV? Can't tell from this sort of analysis. 

The fact that RSV can rise in the presence of influenza virus may speak to its dominance. But take a step back. Remember we're taking about people not cells in a dish. It may be that 2 distinct populations are at play initially; perhaps younger children with RSV versus older children and adults with influenza. Once infected people reach a critical mass, that virus may win out and "push put" the other.What's happening in a single household - kids bringing home one virus, parents another perhaps? That would be intriguing to know with these concepts in mind using molecular methods and longitudinal regular sampling of whole families, regardless of symptoms.

Statistically, when I've looked at this with other data, that negative association, more obvious and frequent between influenza virus and rhinoviruses, does reach significance. You can read one of my group's hospital-based studies in [4] and a collaborative community study in [5]. Rhinovirus seasons usually bracket influenza season. So I offer a different view of how seasonal viruses are seasonal. With the sources of variability I discuss above as well as genetics and differences in everyone's past virus exposures and immune-thing-a-me-whats-it status to each virus, some cross-protective, some not, some having got really sick last year, some not...its not hard to see how those virus seasons can shift around from year to year as well.

Yet another reason to test for viruses, and to include more than just 1 or 2 viruses in that testing; the more you test, the more you can observe and learn.

By the way, interferon-the major player in causing these virus:virus interactions, got its name because it could block a secondary viral infection much like those that I've described above, but on a population level.

Now, try and get some funding to do any research on that. I hate you if you do by the way (yes, I failed miserably).

References...

1. Statewide Weekly Influenza Surveillance Report, 1-January to 8-June 2014.
   http://www.health.qld.gov.au/ph/documents/cdb/influenza-qld-140101-140608.pdf
2. Queensland in autumn 2014: A warm autumn; coastal rainfall but dry inland of the Great Dividing Range
   http://www.bom.gov.au/climate/current/season/qld/summary.shtml
3. Do rhinoviruses reduce the probability of viral co-detection during acute respiratory tract infections.
   http://www.ncbi.nlm.nih.gov/pubmed/19376742
4. Community-wide, contemporaneous circulation of a broad spectrum of human rhinoviruses in healthy Australian preschool-aged children during a 12-month period.
   http://www.ncbi.nlm.nih.gov/pubmed/22829638

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

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

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

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

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

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

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

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

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

It's a numbers game. 

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

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

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Ways in which seasonal and pandemic influenza infections differ

In commenting on another article in the American Journal of Pathology but Gao et al, Kevin Hartshorn nicely summarizes some of the possible reasons why a pandemic influenza kills otherwise healthy young adults more often than a seasonal influenza does. 

The answer is as complex as the milieu of interactions between viral proteins and nucleic acids and our innate and adaptive immune systems, our health, genetic factors, environmental factors and our prior exposure to different influenza viruses - and that's pretty complex!

Hartshorn categorizes the differences between seasonal and emerging influenza impact in young adults using 3 sections:

1. Differences in their ability to cause disease (pathogenicity).
• pandemic influenza generally kill more young adults whereas seasonal influenza kills mostly the elderly and the young
• This is also apparent in ferret animal models
• The viral haemagglutin (HA) protein is key to pathogenesis, playing a central role in pathology due to immune responses and inflammation whereas increases in viral replication are due to the viral replication complex (including PB1, PB2 and PA). Glycosylation of HA is a key pathogenicity determinant because a lack of apical glycosylation allows viral escape from a major non-specific defence; the action of surfacant protein D.
2. Differences in the way the infected host responds to them.
• Pregnant mice and humans show increased severity of disease. This may relate to a reduced innate immune response to pandemic influenza. Bypassing innate immunity may also allow the virus to bypass a key regulatory process, leading to a more over-reactive inflammation.
3. Differences in past history of influenza virus exposures
• Possibly, even with a strong immune cell response, the absence of any prior exposure to a related influenza results in the absence of any cross-protective neutralizing antibodies - the type that can moderate disease - in younger adults compared to older adults. The elderly may have such antibodies from exposures to other H1N1 strains between 1918 and 1957. 

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(formerly pandemic) H1N1 is a seasonal influenza virus these days.

Some people look aghast when I suggest a pandemic virus could now be "just" a seasonal virus...but here is the word from the H�rtl's mouth...

.@pandemie6 #h1n1 is no longer a pandemic but a seasonal virus. it is to be expected that it returns in winter.
� Gregory H�rtl (@HaertlG) July 17, 2013

Printed words from the mouths of others, including some good points, can be found here.

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