Two tales of the same review...

Could these articles about a recent review on Ebola virus transmission be any more different?

Which do you "believe"?

Limited airborne transmission of Ebola is ‘very likely,’ new analysis says Post
From the Washington Post
http://www.washingtonpost.com/news/to-your-health/wp/2015/02/19/limited-airborne-transmission-of-ebola-is-likely-new-study-says/

No, A New Scientific Report Does Not Say That Ebola Is Now Airborne
From Vice News
https://news.vice.com/article/no-a-new-scientific-report-does-not-say-that-ebola-is-now-airborne

The article being referred to is from a team of "Ebola experts" and is entitled: 
Transmission of Ebola Viruses: What We Know and What We Do Not Know.
http://mbio.asm.org/content/6/2/e00137-15

At this juncture might I just add that I do not consider myself a real Ebola virus disease (EVD) expert. I'm just an interested scientist who blogs about Ebola virus and the most recent outbreaks and epidemic. To be an expert, at least in my opinion, one would have to have one or more of the following under one's belt:

• to have conducted experiments on the Ebola virus and written those up in the scientific literature
• to have generated data from other derivative works with parts of the virus, such as in vaccine works, and written those up
• to have treated or cared for patients with Ebola virus disease (EVD)
• to have worked in a public health capacity managing an outbreak of EVD

The rest of us are interested parties but will likely always miss some aspect of understanding the virus and its disease having not been in close contact with it, its hosts or the response to it.

Ebola virus disease: obliterating a variant and stalled case decline...

We've seen the words vigilant and vigilance used widely in recent weeks, ever since we entered a "new phase" of the Ebola virus disease (EVD) battle/fight/war.

The reason for vigilance in all things to do with this campaign has become obvious as the weeks have passed; the reduction in cases has stalled.

I've very crudely drawn in some trends below. Whether you agree with them or not, it is clear that since the fast fall in confirmed cases reported between November-January, it seems to have become very difficult to stamp out the last fires of EVD. 

The phases.
(Very) rough trends in the number of EVD cases over time.
Date from World Health Organization situation reports (SitReps)
and situation summaries (SitSumms).
Click on image to enlarge.

Liberia has come the closest to completing this goal of obliterating the Makona variant of the Zaire ebolavirus (EBOV|Makona) with just 3-9 confirmed cases between World Health Organization (WHO) Situation Report (SitReps) during any of the past 7 weeks. It seems that recent cases can be traced to known transmission chains too and that means no surprise outbreaks. 

However, the people of Guinea and Sierra Leone have not quite got the messages that those in Liberia seem to have embraced (without touching!) so admirably. 

In the last WHO SitRep [1] it was noted that 39-45 unsafe burials (probably not all that occurred) occurred in a week and >40 EVD cases were identified post-mortem. This last observation means exposure of the community to the virus, not getting help and treatment for ill people, and unnecessarily requiring contact tracers to play catch-up. Bad for the infected people their friends and families and the response to EVD. It doesn't have to be that way.

This paints a picture of problems with Ebola outreach and education, communication and cooperation. Those things will keep the latest EVD "phase" chugging along. 

We do need to destroy this variant of Ebola virus by isolating it in the last human cases in each of Guinea, Liberia and Sierra Leone. Once those people recover or regrettably die, EBOV|Makona will be gone, except for what's in lab freezers around the world and in sequence databases thanks to the efforts of a few expert research teams. Once gone from "the wild", the evolutionary clock resets back to the EBOV variants in the animals of the forest.

EBOV|Makona knows too much; it has seen too much; it has learned too much, to be allowed to "live". It has been passed through humans too many times and while there is a vanishingly small chance it will sprout wings, it is still a virus that spreads relatively easily under the right conditions and circumstances. Explosive loss of 8 litres of fluids a day provides many ways to pass along this blood/gastro virus. EBOV|Makona may also have adapted, and continues to adapt, in other ways that would mean its stay among humans becomes lengthy and its dissemination more widespread.

More bad news from an unsuccessful obliteration of EBOV|Makona-smouldering EVD in Sierra Leone and Guinea may release new case embers that drift across borders and set new fires in other countries. We don't need hundreds of cases a day for that to happen.[3] We know cases also fly with the aid of planes (not wings). And the cycle could renew. I don't think we'll see such big outbreaks of EBOV|Makona again, for reasons I laid out here, but chasing new fires is more work than stamping out the remnants of old ones. Vigilance and action. 

I think vaccines still have an important role to play in the final phase of this epidemic, even if only 3 new healthcare worker cases were noted in the past SitRep week. Vaccine given to more than just healthcare workers could be useful here if others will accept the needle.

• Ebola outreach
• Education
• Communication
• Cooperation

Oh, and vigilance.

References...

1. http://apps.who.int/ebola/en/ebola-situation-report/situation-reports/ebola-situation-report-18-february-2015
2. http://virologydownunder.blogspot.com.au/2014/08/behind-naming-of-ebola-virusesnot-yet.html
3. http://virologydownunder.blogspot.com.au/2015/02/cases-of-ebola-virus-infection-can-be.html

Avian influenza H7N9 human infection emerged 2 years ago...

Seems like only 365 days ago I wrote about H7N9 being 1 year old.

Now - it's another year later.

While we have studied, written, read and learned much, much more about this emerging respiratory virus than we have about the Middle East respiratory syndrome coronavirus - even after its 3 years among us - we are still watching a new outbreak of human H7N9 cases spread across China. 

Each year more provinces are added to the list to report human infections - more infections likely go unnoticed, unrecorded and/or unreported. Gaps in the reporting is not unexpected and not unusual. 

Each outbreak with its accompanying economic damage, financial losses, human illness and death is because of the desire to maintain a tradition, namely the consumption of freshly extinguished poultry.

We're really good at getting ourselves into pickles. And we seem to be doomed to repeat the patterns, playing catchup and never getting in front of our new and emerging infectious diseases problems. And each time we seem amazed at what we learn, but really, we learn the same thing over, and over and over again. Eventually we'll run out of infectious threats I guess. 

Or they'll run out of hosts in which to incubate in and spread from.

Happy Lunar New Year.

Gung hei fat choi! & Gong Xi Fa Cai!

..to the Cantonese and Mandarin speaking readers who may stumble across this blog, as well as everyone else who visits!

May all who read this have a happy, healthy and prosperous Lunar New Year, an enjoyable Spring Festival and much luck in the Chinese Year of the goat (mounrain sheep)!

Guangdong sees sense among the feathers...

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

Cases of Ebola virus infection can be exported any old time...

I'm adding my two cents on the issues around remaining vigilant about Ebola virus disease (EVD) cases. 

There are far fewer weekly EVD cases than there used to be but it remains absolutely essential to "kill off" this particular highly-passaged Zaire ebolavirus variant. In other words, push new cases down to zero per day in all three countries, keep it there for 42-days, and thus declare all three nations free of Ebola virus transmission.

Apart from the obvious desire to see these countries rid of this horrible and deadly pestilence, another, less likely thing to consider is that more spillovers to other countries can still happen at any time. And apart from the costs, the reaction from a certain country to its first imported case, just does not bear living through again.

Whether human cases were just kicking off, or after they began accruing at an exponential rate of hundreds per day, the hotspot countries have been the source of export of a case to another country. 

That said, in my opinion we are in a much better global position today than we were six to twelve months ago. We can much more effectively engage and thwart the spread of infection from an EVD case that appears on our doorstep because we now know Ebola virus is out there and can hop on a plane, and many countries and regions within countries have done something to prepare for that rare arrival. Some countries were already in a better position than others, simply because they have (relatively) huge healthcare 
processes in place and are now aware of how to help, and how quickly to respond, should a foreign neighbour acquire a case. 

None of that is to say zero spread in other countries is a given in the near future; humans being humans, accidents and mistakes will always happen. But we are just very unlikely to see EVD spread in a new country to the extent that we saw last year. Hopefully I'm not being too naive on that call.

If we look at the images below, it's plain to see that EVD cases were exported from these countries both early on and late in the outbreaks and later epidemic. Guinea being slightly more of a culprit than the other two countries of intense and widespread transmission (Liberia and Sierra Leone).

Guinea's Ebola virus disease experience. The approximate time at which 
another country receives a person infected by Ebola virus, most likely acquired
from within Liberia, are indicated by an arrow.
Click on graph to enlarge.

Sierra Leone's Ebola virus disease experience. The approximate time at which 
another country receives a person infected by Ebola virus, most likely acquired
from within Liberia, are indicated by an arrow.
Click on graph to enlarge.

Liberia's Ebola virus disease experience. The approximate time at which
another country receives a person infected by Ebola virus, most likely acquired
from within Liberia, are indicated by an arrow.
Click on graph to enlarge.

The filovirus tree has been shooting wildly

While there are not a lot of new branches, there are many, many new leaves on this growing tree. That is overwhelmingly due to the fantastic work of Dr Pardis Sabeti, and Stephen Gire at the Sabeti lab, Harvard University, and their many collaborators. 

It sounds like even more sequences will be coming out in the future. This group is the face of the molecular epidemiology of history's largest Ebola virus disease epidemic in Sierra Leone. If a team of scientists could be said to embody an aspect of an epidemic, it has been these guys and their virus characterization. Hugely impressive stuff.

I only wish we could see more Guinean and Liberian sequences - they are both hugely under-represented in this tree of complete genomes downloaded from GenBank a week or so ago.

Click on tree to enlarge even further.
Coloured boxes surround those sequences generated during the
2014 EVD epidemic. Orange boxes point out the nearest neighbours
and the year from which the sample that was sequenced, originated.
The West African Ebola virus Makona variant has been
traced back to sharing an ancestor in common with a 2007
variant in 2004.

References

1. Genomic surveillance elucidates Ebola virus origin and transmission during the 2014 outbreak. Gire SK, Goba A, Andersen KG, Sealfon RS, Park DJ, Kanneh L, Jalloh S, Momoh M, Fullah M, Dudas G, Wohl S, Moses LM, Yozwiak NL, Winnicki S, Matranga CB, Malboeuf CM, Qu J, Gladden AD, Schaffner SF, Yang X, Jiang PP, Nekoui M, Colubri A, Coomber MR, Fonnie M, Moigboi A, Gbakie M, Kamara FK, Tucker V, Konuwa E, Saffa S, Sellu J, Jalloh AA, Kovoma A, Koninga J, Mustapha I, Kargbo K, Foday M, Yillah M, Kanneh F, Robert W, Massally JL, Chapman SB, Bochicchio J, Murphy C, Nusbaum C, Young S, Birren BW, Grant DS, Scheiffelin JS, Lander ES, Happi C, Gevao SM, Gnirke A, Rambaut A, Garry RF, Khan SH, Sabeti PC.
   Science. 2014 Sep 12;345(6202):1369-72. doi: 10.1126/science.1259657. Epub 2014 Aug 28.

Are fewer Ebola virus disease cases being confirmed than previously?

A very quick graph plotting the proportion (percentage, %) of laboratory-confirmed Ebola virus disease (EVD) cases reported by the WHO over time. That is, the of samples taken from clinically suspected EVD cases that are RT-PCR positive for Ebola virus in a given report, divided by the total number of suspected + probable + confirmed cases in that report.

Taken from my static
EVD tallies and graphs
page here. Updated
28JAN2015 AEST.Click on graph to enlarge. 

Looking at the graph below, it seems like a lower proportion of total cases are being confirmed now compared to before the total case load began decreasing (especially from December onwards-see adjacent graphic). 

Presumably this is due to the larger number of other infectious diseases in the region that cause signs and symptoms, especially early signs and symptoms, that cannot be easily clinically differentiated from EVD; more suspect cases that don't test positive for EVD than before.

When considered in the context of the now smaller number of EVD cases overall, the non-EVD infection's background "noise" has become louder.

But the bottom line is that EVD cases are steadily declining thanks to the many efforts of many people and the changes to habits, traditions and practices that increased risky contact.

The proportion (%) of EVD detection that are laboratory confirmed at each World Health Organization Situation Report or Situation Summary. Anomalous values have been removed. Click on graph to enlarge.

Societal change and H7N9..

The importance of societal change for controlling infectious disease outbreaks really cannot be over-stated. 

For Ebola virus disease, it came down to stopping the tradition of direct contact with the body of those who have died and dircet contact in general. For MERS it

seems that occasional camel contact triggers insertion of the MERS-CoV virus into hospitals where lax infection prevention and control practices add to the case load. 

For influenza A(H7N9) virus cases, it is the habit of obtaining live poultry from retail markets where rare virus-laden chooks are culled and handed over because of a desire to see, choose and purchase the tastiest fresh chicken. 

There is a common thread among these stories about direct contact or inefficiently droplet-transmitting virus infections: we can stop their spread. 

But we also amplify and prolong their spread. 

However, when it comes to human-adapted, efficient droplet-spread or airborne-transmitted viruses - well, then we're in trouble. Of course we could all just lock ourselves in a room for a few weeks but that won't ever happen.

So its very important to head off these "emerging" viruses while we still have a modicum of control over them. Once they get away from that control, and theoretically that could happen in the blink of an eye-right now even-no amount of fancy infra red cameras, poorly donned surgical masks or fancy hospitals laden with machines that blink and go ping, will stop them from spreading globally.

Cheery.

In the meantime - here's hoping China speeds up the closure of those live poultry markets. Habits can be changed but death is forever.

Click on image to enlarge.

Some changes to my Ebola virus disease (EVD) graphs...

To perhaps provide clearer info and to accommodate the changes in the epidemic, namely the reduction in cases and the focus on ridding Guinea, Liberia and Sierra Leone from any and all cases of EVD, I've made some tweaks to my Tableau data visualizations (or dashboards). Briefly...

The dots take their leave.

Was this.

Gone are the dots in my cumulative chart, to be replaced by a third "area under the curve" style graph. 

This brings out the importance of the confirmed cases-more on why that matters later. This week Cedric Moro @Moro_Cedric) asked why we seem to have a relatively large number of suspect and probable cases released in each report World Health Organization situation report (WHO SitRep) or summary (SitSumm). I imagine this is due to the turnaround time once the sample arrives, occasions when results may need to be repeated to confirm strange results, time between seeing a patient and sampling them for Ebola virus testing...but there are probably more obvious reasons. Chime in.

Is now this.

Plot the right data for now.

I'm not an epidemiologist - yes, I know you epidemiologists out there already know that. But I like to play with numbers and pretty colours. So this week I got some information that I didn't have before - the reason why use of cumulative curves was frowned upon by the excellent numbers communicator, Prof Hans Rosling (@HansRosling). 

I had read previously that Prof Rosling was no fan of cumulative curves in graphically explaining progress in ridding west Africa of EVD. But I like them - I've even explained, in my epidemiologically unprofessional opinion - how a flat plateau on a cumulative curve clearly shows the stalling of an outbreak or epidemic. Turns out I either didn't read all of that quote, or the text I read didn't contain the key fact. 

It's not really that cumulative curves are at fault, it's what they are plotting that can mislead. The important thing to plot, especially now that cases are fewer and laboratory capacity is in place, are the confirmed cases, not the total cases which include suspected+probable+confirmed cases.

Confirmed cases are Ebola virus, unconfirmed cases may never be.

In the last WHO SitRep (14-Jan-15) it was noted..

All 54 EVD-affected districts (those that have ever reported a probable or confirmed case) have access to laboratory support within 24 hours of sample collection.

"Access" doesn't mean a result will appear 24 hours after sampling though. But even with this shorter access period, suspected and probable cases are in fact still making up a decent proportion of the total cases reported in even the most recent reports. For example...

• In Guinea the numbers between 14-Jan-2015 and 15-Jan-2015 saw suspected cases rise by 3, probables stayed the same and confirmed cases lifted by 8; 27% of the total cases reported between this pair of reports were not confirmed to be Ebola virus infections, at the time of reporting. 
• In Liberia over this period, suspected cases rose by 29, probables by 2 and confirmed case numbers did not change-so none of the 31 cases were laboratory confirmed as an Ebola virus infection. 
• In Sierra Leone over this period, suspected cases rose by 10, probables remained the same and confirmed cases lifted by 16; 38% of the total cases were not confirmed to be Ebola virus infections.

If we compare those figures to 2 SitReps from well before the WHO had declared the 24 hour laboratory support, dated 24-Sept-2014 and 26-Sept-2014, we find that Guinea only had 8% of its tally unable to be confirmed, Sierra Leone was at 12% not confirmed while 87% of EVD-like cases added to Liberia's tally between reports were not confirmed as due to and Ebola virus infection. 

This may not be a fair comparison of course and it's not one that accounts for every report - just the 2 pairs of reports I arbitrarily chose as being from 'now' and 'back then'. Nonetheless, I expected there to be a bigger and more obvious difference in the proportion of cases that were now being quickly confirmed-I thought that percentage would have gone up as the unconfirmed cases were less frequent. Instead, it seems that the proportion is not that much better. Perhaps this is an indication of the other diseases which mimic EVD early on, that normally emerge at this time of year or have emerged because of the state of healthcare in the countries blasted by the EVD epidemic. As I said above, it may also just be the time it takes to observe, collect a good history and make a clinical decision before a sample is collected. It may also be that laboratory turnaround times (including testing, verifying and reporting) take a bit longer than we naively expect from reading that quote from the WHO above.

More visualizations of confirmed case numbers.

So for the reasons above, I've added the changes I've mentioned and I've also duplicated some of the "total case" graphs by creating versions that only include confirmed cases. 

In the example below I'm showing that it looked like Liberia was experiencing an uptick in cases for 2 consecutive reporting weeks (blue bar graph, right column). I tweeted about this during the week. In fact, those rises were due to unconfirmed cases. The confirmed case plots (green titles in the right-hand column of graphs) show the consistent decline in new EVD cases we had been hearing about. 

Live and learn.

Graphs plotting total EVD cases (including suspected, probable and laboratory confirmed;
brown title bars, left-hand column) versus graphs plotting only the laboratory confirmed cases
(green title bars, right-hand column). 
Data are from WHO SitReps and SitSumms
Click on image to enlarge.