Medical News Blog Information

Influenza in Queensland, Australia: 24-Feb-2014:03-Mar-2014.



Image adapted from Geoscience Australia,
The Australian Government.
Autumn is upon us as the temperatures drop and we've had several days of showery weather in Brisbane.

The Courier mail (and my local radio) media note that "swine flu" (H1N1pdm09 presumably) cases are dominating across Queensland in what may be an early flu season; 85% of notifications are influenza A virus subtypes, and "most" are the "H1N1 swine flu strain". That's the influenza A virus subtype which the northern hemisphere has been battling.


In the previous week's Queensland Health Statewide Communicable Disease Surveillance Report the higher than average number of influenza notification was apparent (unfortunately they don't carry subtyping data).


See my previous post on this uptick in 24-January ([2]; Summer down here). 

By higher, I mean that that there have been 2.4X more notifications in Queensland (840 year to date based on onset date; 85 cases in this reporting week) than the mean number over the past 5-years (the mean for the time period spanning 24-Feb to 02-Mar in the previous 5-year period is 348.8). In fact Queensland seems to be leading the pack for flu notifications this year to date.

This time in past years we have seen these notifications..
  • 840 case notifications in 2014
  • 516 cases by this time in 2013
  • 233 cases by this time in 2012
  • 820 cases by this time in 2011
  • 104 cases by this time in 2010
  • 71 cases by this time in 2009
...highlighting that there have been other large years, but also much smaller (testing bias perhaps?) tallies in other years.

Keeping in mind that these are total numbers, not proportions of samples tested. Presumably this is the basis for the media comments of an "early flue season". Cairns, Gold Coast, Logan and Moreton Bay public health unit areas are the source of notifications and it seems the more recent data add Townsville and Cape York as hotspots.

I guess the next publicly released QHSCDS Report will have these updated total numbers in it so stay tuned. 


At the end of the 2013 flu season, H1N1pdm09 comprised just 15% of all notifications (although most Flu As were untyped), <1% in 2012 [4]. Queensland followed New South Wales and Victoria in total laboratory-confirmed notifications for 2013 [4]. 2013 was a late-starting, shorter flu season compared to 2011 and 2012 [4].

Whatever the small details however - get that flu shot - it will be available from next week. An advertising campaign is about to kick off for flu vaccination but in the meantime have a chat with your GP about flu vaccination options. It really is worth preventing the severe disease, and sometimes fatal disease, that can come along with an influenza infection. Not just for you, but for your children, those around you who are pregnant, your partners and parents as well as for the wider community. 


This is one of the relatively few diseases we can attack with just a simple jab.


References...

  1. Queensland Health Statewide Communicable Disease Surveillance Report 3-Mar-2014
    http://www.health.qld.gov.au/ph/documents/cdb/weeklyrprt-140303.pdf
  2. Influenza in Queensland, Australia...
    http://newsmedicalnet.blogspot.com.au/2014/01/influenza-in-queensalnd-austraia.html
  3. Up to 85 per cent of current Queensland flu notifications are H1N1 swine flu
    http://www.couriermail.com.au/news/queensland/up-to-85-per-cent-of-current-queensland-flu-notifications-are-h1n1-swine-flu/story-fnihsrf2-1226851854384?from=public_rss
  4. Australian influenza report 2013 - 28 September to 11 October 2013 (#09/2013)
    https://www.health.gov.au/internet/main/publishing.nsf/Content/cda-surveil-ozflu-flucurr.htm

An update on avian influenza A(H7N9) virus cases in humans: Week 56

As we currently stand (this minute), there are 389 laboratory confirmed human cases of infection including perhaps 122 deaths (31% PFC). 

H7N9 cases are mostly noted in older males (Average age 54-years; Wave 1 57-years; Wave 2 53-years) with the major risk being exposure to birds and "poultry markets" (commas because it is not just poultry being sold at these markets). No sustained human-to-human transmission has been noted and no specific vaccine exists although one is coming soon apparently. Oseltamivir or zanamivir are useful antivirals while adamantanes are of no use because H7N9 is resistant. to them. The second wave has peaked but we are still seeing a shoulder off the main peak from Wave 2; smaller numbers of cases each week (no longer occurring every day), often from regions other than those with closed poultry markets or with only recently closed or temporarily closed markets.


First chart.
Click on chart to enlarge.
First chart: where is H7N9? It's in Southeast China, most cases having been acquired in Zhejiang province (139/389 cases; 36%) during both Waves of human infection and Guangdong province is currently a very close second place (95/389 cases; 24%).



Second chart.
Click on chart to enlarge.
Second chart: where has H7N9 been focused over time? We can see from this chart that Zhejiang and Guangdong provinces have accrued H7N9 cases most rapidly. While Zhejiang featured in both waves, Guangdong is of Wave 2. It will be interesting to see what happens if there is a Wave 3; without finding and controlling the source of human acquisitions and if the birds with the virus continue to have the virus, I expect we will see future waves.


Third chart.
Click on chart to enlarge.
Third chart: the waves of an outbreak. Wave 1 was 2013 while Wave 2 started in Oct-2013 but really kicked off in Jan-2014. Cases dived in Feb-2014 but there are still sporadic cases being reported each week. The Week (#53) beginning 17-Feb-2014 saw 8 cases followed by 7, 4 and 0 for subsequent weeks. Keeping in mind that there are around 4-12-days (currently averaging 8-days overall) between onset of illness and when a case get confirmed by a laboratory (or reported publicly if no specific lab date is available), we may see a few more cases assigned to the last week of February yet.


Fourth chart.
Click on chart to enlarge.
Fourth chart: Age and sex of H7N9 cases. The age pyramid shows a decidedly upside down pyramid indicating that H7N9 disease is one of the older age bands. It also shows that it is a disease of men morseo than women.


Fifth chart.
Click on chart to enlarge.
Fifth chart: age by week and proportion female. This is an interesting one. There was a dip in the proportion of female cases for the week the week beginning in 3-Feb (right hand y-axis) which bounced back up a week or two later. 

Sixth chart.
Click on chart to enlarge.
Sixth chart: H7N9 cases per day and the rolling average. The decline in Wave 2 cases continues with multiple recent days recently in which no new cases occurred.

H7N9 and human infections: not just a paltry matter

Jones and an all-star cast of colleagues from Hong Kong, Shenzen, Beijing and Tennessee have looked at songbirds and their susceptibility to a human isolate (infectious virus recovered from a human case of H7N9 influenza) H7N9 infection (1).

But before I note the good bits of their study, this paper is one of importance for adding a lot to our understanding of how H7N9 is jumping to people from poultry/live bird/wet markets. It's also a great reference if you want to better understand influenza and birds overall. 


We've read much about human cases of this avian virus having had contact with "poultry" and bird markets and  from that we assume that poultry are the pool in which H7N9 is swimming (reservoir); but where did the poultry get it from (source/natural host)? Its also interesting to note that: 
  1. Very few poultry test positive for the virus; may simply be because of a test-based problem including using a test that is insensitive or sampling from the wrong end of the bird (testing the cloaca instead of throat as was discussed ). 
  2. Looking at the sequences of the H7N9 gene segments suggested that wild birds (bramblings) played a part in the evolution of the virus currently infecting humans in south east China (4)
  3. Pigeons have tested H7N9-positive (2,3)
So it might be that at least some of the human exposures are not from poultry but from other birds.

The authors of this latest article note the songbirds are common pets and so are in close contact with their owners. In the wild, such birds are likely to interact with farm birds.

Some key findings of this new study are:
  • A/Anhui/1/2013 was the strain used for H7N9 studies; it was an isolate from a human but early on and similar to bird (6) strains. H5N1 (A/Vietnam/1203/05) and H3N8 (A/songbird/Hong Kong/SV102/2001) were also used for comparisons
  • Zebra finches (Taeniopygia guttata), society finches (Lonchura striata domestica), parakeets (Melopsittacus undulates) and wild-caught house sparrows (Passer domesticus) were kept isolated for 3-weeks prior to experiments to let any naturally acquired infections burn out; none of the birds had antibodies suggestive of previous infection by an H3, H5, H7 influenza A virus (is that low prevalence normal?)
  • Birds were inoculated with 105 50% egg infectious doses of virus via nose, eye and mouth (that should do it) and then put in the same cages, sharing water and food, with uninfected birds
  • Virus testing was by growth using eggs (3/sample collected)
  • All inoculated birds shed virus (only) from the oropharynx; finches shed most virus at 2-days post inoculation (dpi); parakeet viral shedding could be detected by culture for 2-days and from finches for 6-days
  • Communal water troughs yielded culturable virus; zebra finches shed most virus but water consumption and drinking frequency were not measured and may have differed among bird species
  • No virus could be detected at 8dpi
  • 1 sparrow showed signs of disease and died; 1 zebra finch died without signs of disease (some loss of appetite)
  • Birds in contact with infected birds did not often acquire infection but when they did, they also shed via the oropharynx
  • In finches that were killed for organ testing, virus was mostly found in the trachea; some was isolated from brain and eye tissues of 1 society finch and in the small and large intestine and a high titre form the lung of the other. H7N9 was grown from the brain, lung and intestines of zebra finch. H7N9 was not found in surviving sparrow organ tissues; in the dead sparrow, some H7N9 was found only in the lungs
  • Nearly all inoculated birds mounted a specific antibody response to H7N9 after inoculation. Among the contact birds, 3/3 zebra finches, 1/3 society finches (had highest amount of antibody), 2/3 sparrows and 0/2 parakeets mounted a response to virus indicating that they were infected but did not show signs of illness nor did they shed virus, at least at culture-detectable levels
So songbirds, can be infected by a human H7N9 isolate, they can shed the virus into the environment, they can die (presumably) due to H7N9 infection, 33-66% of songbirds in contact with an experimentally infected songbird acquire aninfection (even if it was rare to grow infectious virus from that contact which may be a sensitivity issue of the testing) and they mount an immune response to the infection. Given that H7N9 acquisition seems to be a numbers among humans, this degree of transmission among birds fits well.

It was also very interesting that water troughs often contained lots of shed H7N9 virus. This is not new in the world of influenza virus but its nice to cross the 't' for H7N9. The authors note that studies of transmission from songbirds to poultry via communal water sources are yet to be conducted. Seems like this would be a very important piece of the influenza puzzle and with broad application to future outbreaks and seasonality in birds via migration. 

Add to all of this that songbirds are present in many markets (thanks to @Crof, @Laurie_Garrett and @debmackenzie1 for supporting info via Twitter this morning; also see refs from Jones et al (1) and a related story from New Scientist (8)) and that older males are a key demographic for keeping songbirds as luck-enticing (and cute) pets. They are also over-represented among H7N9 cases (see adjacent chart). A good fit.

Another recent study (7) shows chickens and quail (a possible amplification host helping bridge the gap between wild birds and poultry) shed a lot of H7N9 after experimental inoculation via an intranasal route. Also, quail (but not pigeons) shed enough H7N9, for long enough, to pass it along to their contacts; less so ducks.

None of this may be very new to some of you, but it's nice to see data that confirm it all for H7N9. After all, as someone reminded me recently on Twitter, data is just how we roll.

It's not hard to see the circle of life for influenza viruses is there for the interpreting and that non-poultry birds may be important intermediate hosts of H7N9 and act as a source of other influenza A viruses. 

Just how many human cases of H7N9 are acquired by songbirds vs chickens/ducks/quail/geese remains unquantified....perhaps unquantifiable.

References...

  1. Possible Role of Songbirds and Parakeets in Transmission of Influenza A(H7N9) Virus to humans.
    http://wwwnc.cdc.gov/eid/article/20/3/pdfs/13-1271.pdf
  2. A summary of Influenza A(H7N9) virus findings in birds and humans
    http://newsmedicalnet.blogspot.com.au/2013/10/a-summary-of-influenza-ah7n9-virus.html
  3. Emergence of avian influenza A(H7N9) virus causing severe human illness - China, February-April 2013.
    http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6218a6.htm
  4. Sunny summer or birds on the wing?
    http://newsmedicalnet.blogspot.com.au/2013/05/sunny-summer-or-birds-on-wing.html
  5. Origin and diversity of novel avian influenza A H7N9 viruses causing human infection: phylogenetic, structural, and coalescent analyses
    http://press.thelancet.com/H7N9genetics.pdf
  6. Genetic analysis of novel avian A(H7N9) influenza viruses isolated from patients in China, February to April 2013http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20453
  7. Role of poultry in spread of novel H7N9 influenza virus in Chinahttp://jvi.asm.org/content/early/2014/02/20/JVI.03689-13.long
  8. Budgies may be behind latest spread of H7N9 bird flu
    http://www.newscientist.com/article/mg22129542.000-budgies-may-be-behind-latest-spread-of-h7n9-bird-flu.html#.Ux5CnvmSx8F

Influenza and chips: tracking bird movements using transmitters

Understanding bird migration is one important aspect to better understanding of influenza viruses. This is because water birds, including ducks, geese, swans, gulls, terns and waders are natural hosts for low pathogenicity avian influenza viruses (LPAI). High pathogenicity avian influenza (HPAI) viruses are mostly assembled in/found in poultry.

Little detail exists on the extent of wild bird movements from wintering areas to breeding grounds and back again, in both hemispheres. An interactive map that presents some of those data addresses some of this.  The map is located on a Food and Agriculture Organization of the United Nations (UNFAO) and United States Geological Survey (USGS; (1)) website here.

While this map does not include analysis of bird movements further southwards, it is clear that the tracked birds have distinct origins and endpoints. There is also visible overlap between different bird's flyways and endpoints. Such overlap represents chances for different viral passengers to be shed and acquired by the migrating birds, resulting in the production of new influenza virus subtypes and variants. At these endpoints there is also the possibility of local birds, poultry, pigs and perhaps other animals being infected by the visiting birds, also creating the possibility for new viral subtypes and variants to result.

Bird migration clearly involves countries all over the world. It is also seasonal. So just how big is the role for water bird movements in the "seasonality" of influenza outbreaks among poultry? I don't know but the answer is influenced by additional variables including the species and age of the birds, their interactions, their previous exposures to influenza viruses, health and immune status, differences between how and where wild birds exist, how and where poultry are farmed and caged and the health and environmental factors affecting virus survivability including humidity and temperature

From our human point of view, we sit at various points along this migratory transmission/acquisition chain, and that shows up when viruses spillover to us and cause overt disease. 

Amazing it doesn't happen more often really.


Links of interest...
  1. FAO-USGS Avian Influenza Projects at the USGS WERC
    http://www.werc.usgs.gov/ResearchTopicPage.aspx?id=17
  2. H7N9 in wild birds...a review of the literature (VDU post)
  3. http://newsmedicalnet.blogspot.com.au/2013/09/h7n9-in-wild-birdsa-review-of-literature.html
  4. UN FAO Avian influenza telemetry studies
    http://www.fao.org/avianflu/en/wildlife/sat_telemetry.htm
  5. Persistence of highly pathogenic avian influenza viruses in natural ecosystems.
    http://wwwnc.cdc.gov/eid/article/16/7/pdfs/09-0389.pdf

Pediatric Medical Education in Mbarara, Uganda

Before my arrival in Uganda I had read numerous articles on commonly seen conditions, spoken with residents and attendings who had previously worked at Mbarara Regional Referral Hospital (MRRH), and did my best to familiarize myself with cultural practices.  However, nothing could have prepared me for the reality of working at MRRH.  I am privileged to train in a country and hospital where essentially no resource or specialist is more than a phone call away.  There is almost always another test or procedure which can be performed to try to reach a diagnosis, and many third (or fourth or fifth) line treatments available before we tell a patient or their family that there are no further options.  At MRRH, the residents and students practice in an environment where they are never certain what resources might be available that day � do we have patient files or order forms, oxygen available for those in respiratory distress, or appropriate antibiotics for any of the numerous infectious processes encountered daily?  The answer is dynamic, changing from one hour to the next.  Too few nurses leads to the residents and students checking vital signs on rounds and family members administering most oral medications and alerting care providers to changes in a patient�s condition.  There are limited diagnostic tests available, and the providers learn to live with a high level of uncertainty. 



Many of us chose careers in healthcare because we strive to improve the health systems that we work in (locally or globally), but particularly in settings where we see such overwhelming need it is challenging to know where to begin, and many of our well intentioned efforts may have unintended or unexpected adverse outcomes.  The reality is that no matter what one�s prior experiences are, it requires a significant amount of time to adjust to a new way of life and practicing medicine, and even begin to understand the people you are caring for.  
View of entrance to Mbarara Regional Referral Hospital and Mbarara University of Science and Technology.
Outside you can see multiple "boda-boda" motorcycles waiting for potential passengers,
often 2-3 per vehicle and many traffic accidents result from this.

Throughout my month in Mbarara, Uganda working on the Pediatrics ward, I often reflected on how my involvement impacts the healthcare providers and the patients.  I am still a resident � I have no further subspecialty training, or particular expertise to offer to my colleagues at MRRH.  But what residency does prepare you for is learning how to approach patients and formulate a differential diagnosis and a plan, to navigate areas of uncertainty in your knowledge base, and to advocate for your patients and seek out assistance when something is beyond your capability.  You learn how to work with your colleagues to improve systems and share knowledge, and how to supervise while also teaching interns and medical students.  These skills are vital and universal in the practice of medicine, so focusing my efforts in working together with my Ugandan colleagues in medical education was a natural fit.
Walkway between hospital wards
In Uganda, undergraduate university and medical school education are combined into a five year program.  Years 1-2 are pre-clinical and principally didactic and then year 3 is the first year spent on the wards rotating through the primary specialties.  Interestingly, the fourth year is the �community� year, where students are assigned to work in various rural locations throughout the country in local health centers, alongside village health workers, and are even exposed to traditional healing practices.  The goal of the 3rd year, as it was described to me by one of the senior pediatricians on the ward, is to allow students who oftentimes grew up in more urban environments, to understand the reality of the living situations of many of their future patients - to fully appreciate the hard work and patience required of growing millet, the challenges of safely storing chemicals like organophosphates in a single room thatched hut with no shelving, and why a woman might not make it to the health center 1km away when in labor, because that kilometer is up a steep hill on a treacherous road during rainy season.  During the 5th year the students return to the wards for advanced clerkships.  During this year they will also be applying for paid internship spots where they will spend 3 months each on Internal Medicine, Surgery, Obstetrics and Gynecology, and Pediatrics.  After internship, the young doctors will typically work as medical officers until if interested and they are able to save up enough money, they may decide to return for their Masters in Medicine, or post-graduate education somewhat equivalent to a US residency to further specialize. 
Pediatric Lab area
While on Pediatrics, each week we would have a new group of 10-12 3rd and 5th year students arrive.  Each morning these students would round with the senior post-graduate, the intern, and me and then in the afternoons I along with other post-graduates and attendings would dedicate time in small groups with the students to allow them to �clerk� presentations.  In other words, we would listen to their presentations of the history and physical for patients they had admitted, discussing the differential diagnosis, and questioning them on their thoughts regarding evaluation and management of the patient.  Many things stood out to me during these sessions.  First and foremost, they impressed upon the students the importance of understanding every patient�s background.  Each presentation began with demographic information about the community the child came from, the tribe they belonged to, the occupation of their primary caregiver, the location of the nearest health center, and the cost to the family to transport the child to the hospital (typically by motorcycle called a boda-boda).  Given the limited diagnostics available at MRRH, a large emphasis is placed on the nuances in the history and details of the physical exam (Changes in the hair pattern or color? Grade of digital clubbing? Characterization on palpation of an abdominal mass?).  These basic skills are the foundation of the practice of medicine, and the ritual that unites the doctor with their patient, yet too often in the United States we find ourselves buried in computer screens or piles of documentation rather than looking at the person sitting right in front of us and listening to their story.  Lastly, the students were quite astute in their understanding and application of pathophysiology � when discussing jaundice the conversation wouldn�t just involve the total and direct bilirubin, liver function tests, and the ultrasound results- we would also review the breakdown of red blood cells and the points at which it is bound or converted, differentiating between forms that are excreted in the stool and the urine, and how these different processes are distinguished clinically.  This learning environment was a tremendous amount of fun and at the same time a great challenge to me as it required me to rely on my knowledge and skills as a clinician and teacher, rather than the myriad of technology I am used to having at my fingertips.
Rescuscitation equipment
As someone who is not an expert in the common conditions afflicting many patients at MRRH (malaria, TB, HIV, typhoid, malnutrition), I concentrated my efforts on helping the students and interns broaden their differential diagnoses and plans for management.  In a practice environment with limited diagnostics and where the ultimate diagnosis often remains uncertain, the tendency can be to focus (appropriately) on what is more readily detected or treated.  However, in a child whose clinical condition can rapidly change from one moment to the next, particularly when there is limited monitoring capability, prematurely narrowing in on a specific diagnosis can be devastating.  Additionally, due to the high acuity of illness there is often a focus on the acute presenting condition, but it can be very important to think about a child�s development and chronic co-morbidities in trying whatever way we can to prevent future complications.  These are teaching points that are of course emphasized by the Ugandan physicians as well, but cannot be overstated.
When it came to working with the post-graduates, I often found myself wondering what I could possibly have to add.  They are some of the brightest, most resourceful and hardworking people I have ever met, and to me, they are the strength and capacity of MRRH.  In getting to know them I found that they enjoyed being able to just discuss challenging cases, talk about differences in how we manage conditions, review how to read radiologic studies (since they less commonly have access to these), and just share general information such as how we run journal club conferences.  I don�t think you can underestimate the impact of building these relationships, and even just beginning to understand the day to day practice in another hospital.

Bins for collection of files with stack of patient files (to the right, green)
On my last day, one of the students said to me that he hoped I had learned as much from them as they had learned from me.  It was the exact thought I had in mind, and I think if we can continue to teach and learn from one another we will both be better physicians.  I look forward to continuing to learn from and with my new colleagues in the years to come. 

Thank you so much to Partners Center of Expertise in Global Health, MGH, MUST, and MRRH for your support in this tremendous experience.

Best,
Meredith Eicken, MD
Internal Medicine-Pediatrics, PGY-3
Massachusetts General Hospital

Guangzhou reopens live poultry markets: Good idea or too soon?

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
  4. China.today Guangdong Province weather
  5. Shenzen shopper weather

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