H7N9 numbers....no-one agrees...

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On Zika and microcephaly: causality, consensus and checklists....

Over the past month the World Health Organization (WHO) and then the United States Centers for Disease Control and Prevention (CDC) have associated infection of by Zika virus (ZIKV) with cases of microcephaly and central nervous system disease (M&CD).[1]

The first WHO statement cited a scientific consensus identified at a meeting called to examine the evidence linking ZIKV infection with foetal malformations and neurological disorders.[1] Later in March the WHO pointed to case studies as the origin for that scientific consensus.[2] I've talked about my views on gaps in some of these studies before - for example here and here.

The CDC based their much stronger comments on a review of the literature and its application to address historically robust checklists - Shepard's criteria and the Bradford Hill criteria - that have heretofore proven themselves useful to identify teratogens (causes of embryonic malformation).[3] The CDC authors of this paper note that there is no "smoking gun" at this point and Dr Tom Frieden, CDC Director said it could take years before answers to other questions are found.[12] But not about ZIKV causing microcephaly. That question is answered according to two of the world's leading public health agencies. 

Checking the checklists.

The checklists CDC used were applied to resolve the questions around the cause of an apparent surge of M&CD diagnoses - the so-called congenital Zika syndrome.[4,5] To date this has been almost exclusively occurring in north east Brazil. Some instances have been reported in other countries with current - or past - ZIKV epidemics, but the numbers are small enough for questions to linger about whether these represent part of "normal" M&CD figures, perhaps brought to attention because of the enhanced focus on congenital deformities in 2015 and 2016 or ZIKV-caused disease.

Shepard noted in 1994 that..

"the rare malformation/rare exposure 
or case report method is far easier, 
less expensive, and more common than 
full epidemiologic studies."

He described "Examples of this rare defect/rare exposure "proof" (or better stated strong association)"[sic] including the virus driven congenital rubella. I'm not sure about rare in terms of ZIKV infection tough. While data are near on-existent from Brazil, we've been told that over a million people have been infected with ZIKV.[19] That seems to be a much less stringent use of Shepard's criteria than that of the CDC's "no longer any doubt".[12] Shepard's criteria have gone on to be used in legal definitions [7] which also take a broader view on causality in the study of teratology..

"causation is demonstrated between an 
exposure and an outcome if the outcome 
would not have occurred but for the exposure. 
The but-for test is typically modified by a 
substantial factor test, that is, the 
exposure was a substantial factor in 
bringing about the outcome, or by 
consideration of the exposure as a 
contributory cause"

The other checklist was the tabulated criteria of Bradford Hill, described in 1965 in his occupational medicine-focussed paper, The Environment and Disease: Association or Causation? which sought to relate sickness, injury and conditions of work.[18] I find Bradford Hill's comments in the Experiment section of his criteria interesting as they discuss whether a preventative action in fact reduces the frequency of the event...

"Here the strongest support for the
causation hypothesis may be revealed."

The CDC interpret this wholly in relation to an animal model.[3] Perhaps this meaning has evolved in subsequent analyses that I admittedly haven't read, but I see this criterion differently. To me it is addressing the need to wait and watch for any impact on reduced mosquito breeding and presence either because of seasonal variation or human interventions; a long wait.

In a statement similar to Koch's about his postulates, Bradford Hill stresses that none of these criteria can be used as if they were set in stone and none bring indisputable evidence for or against a cause-and-effect hypothesis. They are intended to..

"help us to make up or mins on the fundamental 
question - is there any other way of 
explaining the set of facts before us, is 
there any other answer equally, or more, 
likely than cause and effect?"

This seems - to me at least - at odds with the CDC's strident use of these criteria to define causality here.

Neither checklist necessarily hits the mark perfectly for what we're seeing in Brazil but, as with Koch's original postulates, these have been "matured" and tuned over time to fit the need of the moment-presence of a common virus infection causing a rare syndrome. 

Is the strong language essential to a response?

But let's back quietly out of the courtroom and return to the world of science, research and causality. We don't have a smoking gun but that has not prevented some important triggers being pulled. Principal among these was that the WHO called a Public Health Emergency of International Concern (PHEIC) on the 1st of February 2016.[8] Well before the need to use stronger language in March 2016, the PHEIC generated recommendations [9] for...

• To interrupt ZIKV transmission using enhanced surveillance, diagnostics, risk communication, vector control measures, counselling and more
• research and develop vaccines, therapeutics and diagnostics and increases  relevant services in affected areas
• provide uptodate advice on travel to affected areas, disinfection of aircraft but do not restrict travel or trade
• ensure rapid and timely reporting and sharing of information of public health importance relevant to the PHEIC

Obviously those things are expensive. We know from recent experience that the WHO struggled to get the pledged funds they'd requested to mount for an effective Ebola virus disease reposes fast enough and to match the requested spend. Perhaps stronger language is intended to free up the purse strings.[10,11] The main sigh of relief outcome from making such a strong statement by the CDC was...

"Now that we've determined the causal the 
relationship, we can use this information to 
redouble our efforts to prevent Zika, more 
narrowly focus our research and communicate
 even more directly about the risks of Zika."

And herein lies one of my concerns. Narrowed research, by definition, could miss things that have contributed to congenital Zika syndrome. Things that might include...

• other viruses - rubella and cytomegalovirus are teratogenic viruses that are sometimes sought and not often found but that search can use a hodgepodge of methods. But what about new viruses and new variants of existing viruses? 
• the impact of chemicals or toxins - the pesticide issue has not gone away [13]
• the very complex immune responses that to date have mostly been a topic for discussion as a problem for antibody detection in the lab, but may be a part of the process [14,16] although did not seem to play a role in Guillain-Barre syndrome [15]

But all those things may still be included in a narrowed research focus. Those things aside we do know that ZIKV loves to grow in epithelial cell-derived neural stem cells; there is a lot of IgM antibody to ZIKV in babies born with microcephaly [20] and ZIKV has been found in the brain tissues of foetuses with disease.[21]

Devil's advocate - what other things might we consider?

We have not yet addressed whether ZIKV is just as harmless as we used to think it was and whether it is found in these tissues as a passenger and not a pathogen. 

Might it also be in the brain tissues of ZIKV-infected foetuses who do not develop any congenital anomalies? There has been little or no exploration of controls in most papers to date. Mostly - this would be unethical, but there might be other reasons for related tissues to be sampled which could then be leveraged fro important testing. Its important yet missing information.

Excerpted from WHO Zika virus microcephaly
and Guillain-Barre syndrome situation report. [17]

There is also the Colombian elephant in the room. 

This week saw the number of M&CD diagnoses in Colombia double...okay, from 2 to 4... having decreased the week before. This might be normal and part of the 140 annual cases reported in Colombia annually-that's an average of 2.6 per week. 

More time has now passed in Colombia than had in Brazil before Brazil reported its first concerns - and 141 M&CD diagnoses - over ZIKV and M&CD, after it identified local ZIKV transmission. As I've discussed previously, there could be many reasons for that difference - and a rise in cases in Colombia this week may herald that the starting line has been crossed indicating the beginning of some important supporting evidence for ZIKV causing M&CD. Or we might just be seeing normal levels of M&CD that also happen to be ZIKV infected-during an epidemic of ZIKV.

To my mind, the studies used to check off the lists leave some important things unanswered. Patience might have been advisable since the previous announcement of a PHEIC mean that there was no obvious need for the issue to be forced. Or perhaps this is more about the politics of finding a better way to secure the funding needed to address congenital Zika syndrome, and avoid the pitfalls of funding gaps dug during the fight to contain Ebola virus syndrome.

Only time will tell whether such strong WHO and CDC language was needed, helped or even hindered the response and understanding of congenital Zika syndrome. 

References...

1. WHO Director-General briefs the media on the Zika situation
   http://www.who.int/mediacentre/news/statements/2016/zika-update-3-16/en/
2. Zika situation report 31-March 2016
   http://who.int/emergencies/zika-virus/situation-report/31-march-2016/en/
3. Zika Virus and Birth Defects — Reviewing the Evidence for Causality
   http://www.nejm.org/doi/full/10.1056/NEJMsr1604338
4. http://www.bbc.com/news/world-latin-america-35763232
5. http://annals.org/article.aspx?articleid=2498549
6. "Proof" of Human Teratogenicity
   http://onlinelibrary.wiley.com/doi/10.1002/tera.1420500202/pdf
7. Causation in Teratology-Related Litigation
   https://www.teratology.org/pubs/Causation_Ter-Rl_Litigation.pdf
8. http://www.who.int/mediacentre/news/statements/2016/emergency-committee-zika-microcephaly/en/
9. http://www.who.int/mediacentre/news/statements/2016/1st-emergency-committee-zika/en/
10. http://www.globalissues.org/news/2016/02/01/21800
11. http://www.oxfam.org.uk/media-centre/press-releases/2016/01/international-community-fails-west-africa-yet-again-ebola
12. http://www.cdc.gov/media/releases/2016/t0414-zika-update.html
13. https://peerj.com/preprints/1959/
14. http://www.sciencemag.org/news/2016/03/qa-scott-halstead-zika-will-subside-5-years-max
15. http://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(16)00562-6.pdf
16. https://www.statnews.com/2016/02/17/zika-dengue-infections/
17. http://apps.who.int/iris/bitstream/10665/205505/1/zikasitrep_21Apr2016_eng.pdf?ua=1
18. The Environment and Disease: Association or Causation?
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1898525/pdf/procrsmed00196-0010.pdf
19. http://www.reuters.com/article/us-health-zika-brazil-exclusive-idUSKCN0VA331
20. http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)30253-7/fulltext?rss=yes
21. http://www.nejm.org/doi/full/10.1056/NEJMe1601862?af=R&rss=currentIssue

Avian influenza A(H7N9) virus case data in humans: more chicken scratchings

This is an example of a 2015 case announcement from the World Health Organization (WHO). I think it aims to provide information on some avian influenza A(H7N9) cases that occurred in China.

From WHO Disease Outbreak News (DON) at
http://www.who.int/csr/don/15-june-2015-avian-influenza-china/en/

I suppose it does do that in the most basic sense. Yes, if you were a casual electronic browser to the WHO disease outbreak news site (...get out more!) then you would learn of 15 additional human cases of disease presumably due to H7N9 infection. Twenty percent of these cases died and this happened within a month. 

But consider these questions for a moment:

1. Why would you visit the WHO to learn of this, if you were not seeking some actual detail and evaluation of risk?
2. If you were a casual browser, I expect you would come away from this with some out-of-context concerns about a bolus of cases in such a short period, spanning a wide age range and occurring across considerable geographic distance. Should you be worried? Is this the precursor to some larger outbreak? Each difficult to answer from this very small cross-section of information.
3. These public data are relied upon by some when they write papers or release infectious disease reports - so why not include key - yet deidentified - demographic detail in a line list format - remember MERS-CoV in South Korea anyone? That WHO list [4] was messy [5] but it was a step forward for those outside the WHO network who wanted free, publicly available basic data, quickly

In my opinion, the premier emerging disease tracking and publishing - at least in terms of accessible, basic, rapid, searchable, freely accessible and up-to-date emerging infectious disease information - is the team at FluTrackers. Keep your predictive modelling - I'd trade it all in for a clone army of these guys any day! The FluTrackers line list on H7N9 includes some of these cases[6]...and as you can see in the snippet below, even their scouring of the media from China does not help to fill in the data gaps on these cases...

From FluTrackers' H7N9 line list at
https://flutrackers.com/forum/forum/china-h7n9-outbreak-tracking/143874-flutrackers-2013-15-human-case-list-of-provincial-ministry-of-health-government-confirmed-influenza-a-h7n9-cases-with-links?t=202713 [6]

So why does the WHO bother with this information at all? I can't speak for them. But one reason may be because it is relied upon by those who study and prepare for the emergence of new or re-emergence of old infectious agents.[1] These people consume this sort of information to track what's happening outside their own back yard and to weigh the risks that a new bug may come knocking at the gate thanks to a speedy international plane flight. But when the host country is slow or perhaps even reticent to identify key case details, a knowledge gap emerges and may widen. This particular gap has been growing since 2014's H7N9 3rd wave. Perhaps since the 2nd wave.

When sufficient - or any - detail is lacking, then it comes down to the public to look for any answers they seek...by themselves. In this case, that has been FluTrackers & Co; this source has proven itself very worthy for this and for other viral threat monitoring, but cannot be expected to fill this need indefinitely.[2,3]

H7N9 is a good example of an absence of obvious change to the flow of information that the world's public, citizen scientists and its more professional scientists receive about new infectious threats. And this is all a bit strange because I was sure we'd heard a lot about the need to do much, much better on this sort of tracking and chatting in 2014/5 during one of the biggest modern moments of being "caught with our pants down" - the Ebola virus disease epidemic.

Time and viruses wait for no person. Be faster.

Ho. Ho. Ho.

References...

1. http://ecdc.europa.eu/en/publications/Publications/RRA-Influenza-A-H7N9-update-four.pdf
2. http://www.ncbi.nlm.nih.gov/pubmed/24885692
3. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4140362/pdf/jphr-2012-2-e29.pdf
4. http://www.who.int/emergencies/mers-cov/MERS-CoV-cases-rok.pdf?ua=1
5. http://virologydownunder.blogspot.com.au/2015/06/matching-mers-case-identification.html
6. https://flutrackers.com/forum/forum/china-h7n9-outbreak-tracking/143874-flutrackers-2013-15-human-case-list-of-provincial-ministry-of-health-government-confirmed-influenza-a-h7n9-cases-with-links?t=202713

Ignore mild and asymptomatic cases at your peril...

Infected but apparently well people may be key points along the transmission chain - not just in spreading infectious virus, but also in contaminating surfaces.

Or they may have no role in transmission at all.

When you have problems that weren't solved by the easy answers - look harder.

Study. Test. Find out. Communicate.

Knowing the full story of how a virus spreads is hard work. But transmission is not necessarily a simple process. Like everything biological, it may be more complex than we care to acknowledge. Such a complex scenario is shown here. Completely fictitious.
Or maybe not.
Testing can answer questions. Communication can provide answers.Click on image to enlarge.

Ebola virus disease, getting ahead of communication needs and WHO

Editor's Rant: Communicating the data and about the data...

It is pretty damn hard work trying to get hold of data on virus outbreaks around the world. 

When it is, it may be available in unfriendly formats. It may not be made public at all. When it is available, it is often slow to appear or it may have random reporting gaps, or be partially incomplete. The style of the released data can change overnight as well, sometimes going from detail to summary.

So why bother about trying to get hold of these numbers at all? It's not like I work in the field. Well, that is a question I'm increasingly asking myself of late too. My personal reason has been because I think there need to be more voices in the vacuum between the numbers being reported and the often dry public health reports. I think scientists, even if they are not lifetime experts on a given virus or outbreak, still have much to offer when they come out from behind their manuscripts and apply their skills to interpreting what's happening. Well, many do anyway. And they should do it more. Now, perhaps more than ever, science needs steer away from its cold, dense and boring niche writing to a chattier, more helpful and community-based style of engagement. It astonishes me how often the public's interpretation of outbreak numbers must come from the media or from hobbyists, or even professionals who work in other areas and give of their own time to help explain something to us in their personal time. Helpful and engaging information and better access should come from the source of the data.

So it becomes really annoying (you would have to know me quite well to know how many times I just rewrote those words) when data are given out for public use that are a total mess...and there is not one tiny mote of explanation for it. I called it appalling on Twitter tonight. And at other times there are no explanations for why there are gaps, why data are delayed, why the format may have changed today compared to last week, why a line list is missing a case, using a new and totally independent numbering scheme or suddenly reshuffled, why there is no news about a new outbreak. No word. No contact. No-one taking the lead. No...communication.

I have met a lot of people since I have been blogging who, in various ways, have put in their own personal time to help out bigPublicHealth, to help take up the slack in communicating to the media and to the public. It is hard to quantify the impact of that combined help-but I can assure you that it reaches far and wide and is not insignificant. One would think that it should be easier to provide this help when one is willing to make use of their own time and use their own resources, or that those people should be shown enough respect to be able to simply find and apply reliable raw data so they can help out. But one would be an idiot. I very clearly remember a time when I could send a public Tweet to WHO's Head of Public Relations, Gregory Haertl, and get an informed reply. Those days have passed. I remember there being an #AskEbola channel on Twitter that gave answers. That engagement is just not there anymore. I'm sure its funding and resources and blah blah...but not as sure as I could be if that were spoken about in public. Communication. Someone needs to step up on this. As the quotes above allude to, 2015 is not 2014. And one of those differences is that everyone wants timely and comprehensive information they can rely on during times of outbreak. This hasn't been discusses enough but it should be.
 

Matching MERS case identification numbers from two differing sources...

Update #1 27JUNE2015
Update #2 28JUNE2015

Sometimes people work from different playbooks.

Figure 1. MERS in South Korea. Most cases now plotted
on graph using their dates of illness onset.
An outbreak in decline. This is up-to-date - 3 new cases
from 21JUN2015 added (column at right hand side -
onset dates unknown)
Click on graph to enlarge

In this instance, the data from the World Health Organization's (WHO) new list of Middle East respiratory syndrome (MERS) cases - with extra detail - uses a case identification key that's out of synchrony with that produced by the South Korean (SK) Health Authority which can be found in each of its posts announcing new MERS cases and deaths. 

Attempting to link the two lists has mostly been an exercise in pedantry, but sometimes it is useful to know which case one is talking about when discussing an outbreak or cluster of disease....'Hey Bill, what didja think of that 70 year old MERS case who drove the ambulance carrying that infected 75 year old MERS case and then those others got MERS as well..?' doesn't really roll off the tongue does it?

Figure 2. What the graph above looked like before
we had dates of illness onset. Many cases
were 'moved' to earlier time points because
report dates always follow onset of illness dates
and they can follow by varying periods of time -
sometimes a day, sometimes a week or more.

Two file formats are in the folder I've linked to below. This is my first attempt - yes, it is a work in progress - to match up the new WHO case list from the 19th June which includes the highly prized date of illness onset (DOOs) for most cases - with that of the South Korean (SK) Health Authority. They do differ. Quite a bit. And in several ways. For example, the numbering scheme is off by one or more, SK69 seems to be missing from the WHO list, there is a question mark hanging over SK152 & SK156 and the WHO data seem to have a number of different ages from the SK data- mostly differing by one year (presumably someone is rounding up or down). 

If I've stuffed anything up or if you can solve my problem cases - please pass that info along and I'll update the files on this page. Hopefully the next WHO version will have addressed all of this anyway (it didn't but perhaps a future one will).

These are publicly available and you can download them for your own interest.

There is a download arrow at the top of the Google Drive page.

1. Google Drive folder with MERS data files
   https://drive.google.com/open?id=0B5sEcTjB5Ailfm1PcU1oNDF6M2hiaDduUDgzQUdxNlZxeHBkU0FHeVBRRFJkbHIxTmdjX3c&authuser=0

Updates...

1. With the help of FluTrackers updated line list to cross check against, the first half of my list has been updated - some bugs fixed. 
2. After about 5 hours - on and off - FluTrackers helped me sort out a few errors and the latest version of my list has been uploaded into the the folder linked above. Some typos corrected.

MERS-CoV in South Korea - other data formats for data provided by WHO...

The following links take you to different version of the PDF if you want to harvest those data...

1. Excel version, Office 2010
   https://drive.google.com/open?id=0B5sEcTjB5Aila3c5WXI4bzlkLWc&authuser=0
2. MS DOS CSV file
   https://drive.google.com/open?id=0B5sEcTjB5AilTHRub1FRZnhpQmM&authuser=0
3. Original WHO PDF
   https://drive.google.com/open?id=0B5sEcTjB5AilWlo0UDZwVzRpdVE&authuser=0

Its taken a week to get these data, and its unclear why detail data dried up from the 12th June to the 19th, or why the data have appeared now, but they are here at last and that's great.

Translating from the Korean for MERS epidemiology...

I absolutely love the graphic the Korean Broadcasting Service (KBS) have been putting up. Love 'em. Great job!  I just wish they were in English too. I understand that the first priority is to your own population - totally get that. But I do wish that, like the Saudi Ministry of Health, every country could do an English version as well as the native language. 

But processes, time money and stuff...

Anyway - to help me try and get more detail on the South Korean clusters I have added some translation to one of the KBS pages which, when you click on the icon of a person, gives you a popup box with some detail. I've added translation to the contents of that box (see the figure below). 

I don't know how accurate the "Date of infection" field is but will be comparing it to the World Health Organization (WHO) data from earlier to see if it can be useful. This is all because the date of reporting is almost always different from the date of illness onset - and the latter are much better to plot to get an idea of whether an outbreak is rising, peaking or slowing. Having the ability to crowd-plot these numbers is great and (I think) useful to inform the public and our clinical and scientific peers when included alongside some discussion about trends and reason for changes, risk etc. Often (always?) more personable banter, and engagement, seems to be lacking from 'bigPublicHealth' sources.

Click on image to enlarge.
Adapted from http://dj.kbs.co.kr/resources/2015-06-08/[1]

This sort of data mining seems essential if the recent WHO publication of a minimalist 33-word summary of the last 62 cases is now the norm - or perhaps the provision of information from the South Korean health authority to the WHO has changed in format. And that has become acceptable to the WHO, who have not commented on the change. Such summaries, and lack of comment, are also business-as-usual for 'updating' us on human cases of influenza A(H7N9) virus in China.

References...

1. http://dj.kbs.co.kr/resources/2015-06-08/

Liberia gave Ebola the boot...and a virus may soon be removed from the wild

The people of Liberia have earned our respect, some time for national celebrations and frankly any other rewards that may flow from denying the Makona variant of Ebola virus any hosts among their community. 

The world considered this viral species to be one of the list-toppers when it came to ranking the causes of the most scary acute infectious diseases. Ebola virus has been the basis for all sorts of 'end-of 'the-world' mutating virus horror movies, books, and TV shows. It's not at all surprising that the public view of an Ebola virus infection had long been one of blood, fear and terror.

Figure 1. The decline of the Makona variant of
Ebola virus in Guinea, Sierra Leone and Liberia
(now free of EVD transmission).
Click on image to enlarge.

Behavioural change was a major factor in reducing virus transmission in Liberia. Alongside that was a broad range of aid given from within and beyond Africa's nations. By working together, a widespread outbreak that was not initially thought likely to happen at all, was routed. 

For now. 

Liberia is not immune to new cases of Ebola virus disease (EVD) crossing its borders or popping up due to a new animal-to-human jump (a zoonosis). That could happen any day - it might be happening now. But those who are still on watch will be searching out new cases while the remaining sites of transmission - Guinea and Liberia - do their best to deny Ebola virus a chance to replicate and spread. The people of Liberia will keep watch help because they have learned very tough lessons about viruses, epidemiology and communication. At least 10,604 suspect, probable and confirmed EVD cases, 4,769 deaths and way too many stories of sadness and families destroyed are a very strict teacher. 

Figure 2. The number of confirmed EVD
cases (yellow) grinds to a standstill. Only
9 cases in the week to 10th May 2015.
Click on image to enlarge.

The crude prediction in Figure 1 suggests that zero cases across all three countries could happen at the end of May, but many stars must align for that to be a real event. 

Human factors - the causal and sustaining variables of any outbreak of infectious disease in humans and sometimes animals - remain very much in play. But once that tri-country zero case value is attained, we have 42 days of watching and waiting - from the time the final case tests negative. 

New cases may arise from sources as-yet-unknown. But even if they do keep popping up, it seems very unlikely that widespread transmission will amplify to earlier levels (see the steep slopes in Figure 2) unless a major lapse in attention occurs. Hence,the need for continued vigilance - and Liberia remains on alert for a further 90 days. That more recent figure comes about because we know that infectious Ebola virus can persist in some body sites for many weeks after signs of disease have passed. Whether that virus reservoir is present in every person and whether it actually does cause new Ebola virus infections remain unproven. When you consider what can happen when one person gets infected by an Ebola virus in a tiny remote village in a country that is ill prepared to cope with it and has traditions that lend themselves to its spread...even minor risks rightly come under more intense scrutiny.

What next for this particular virus though? The only place where the Makona variant of this member of the Zaire ebolavirus species will soon exist, is in the freezer of (hopefully) very biosecure laboratories in the US, UK, Africa, Russia, China and probably other laboratories in countries that hosted, evacuated or repatriated cases of EVD. 

There is no sign at all - and this is because of the continued efforts and focus of many currently working throughout west Africa - of the fabled "endemic Ebola" becoming a reality. Unless you mean enzootic 'Ebola'- in which case , it already is, I suspect. It seems very, very likely that the forests of west Africa continue to shelter animal hosts with less mutated versions of this and other ebolaviruses (and filoviruses and who-knows-what else). The host species and route(s) of transmission to humans are yet to be confirmed but for now, we are not too far off eradicating one unwanted viral scourge from the wild. Impressive what we can do when we pull together.

Ebolaradication around the corner..?

The downward trend for new, confirmed, Ebola virus disease (EVD) cases continues as we can see in the graph below.

This graph plots the number (each blue data point or dot) of newly confirmed cases in each World Health Organization situation report of summary. The joining lines don't mean anything (the WHO doesn't provide any numbers to place between dots)- they just make it cleared how think go up and down. You can see a little about Monday'itis and its role in the bumpy road to zero cases here.

Below is part of one of the charts from my Ebola virus disease numbers page -  you can get to it from any page on this blog by clicking on that tab up there^.

The line indicating the linear trend of fewer cases over time has a p-value of  0.023 and was
calculated within Tableau Public Edition v9.0
Click on image to enlarge.

I've zoomed in the graph to highlight distinct data points (thanks to Ramon i.e. @HlthAnalysis for helping me learn to make the separately coloured dots I missed so much from my Excel graphs). Without the zooming we can see from the full dataset that it's getting a bit hard to see each data point as time goes by, and case numbers shrink (yay!).

WHO reconsiders openly wanting to be a new organization

Yesterday I stumbled across this statement by the World Health Organization (WHO). It's reprinted in full below, but the original version is no longer on the WHO site (more on that in a minute).

It was a powerful human, feeling, mea culpa on the Ebola response along with a very strong and detailed plan to move forward and a fiery desire to be the group that keeps the world safe. I tweeted a few bits of it and stated my respect.

Hey @WHO If we all admitted our mistakes & openly spoke of ways 2do better-what a wonderful world it wouldB! #Respect http://t.co/a7NjzH70Ou
— Ian M Mackay, PhD (@MackayIM) April 20, 2015

"Hold us to account" Joint statement on the #Ebola response and @WHO reforms http://t.co/ihVLWLDcZ7
— Ian M Mackay, PhD (@MackayIM) April 20, 2015

"there were shortcomings in risk communications" via @WHO #EbolaResponse http://t.co/a7NjzH70Ou
— Ian M Mackay, PhD (@MackayIM) April 20, 2015

Then I noticed some tweets, including this from @cymeaton indicating that the WHO had released a new and different version.. (also story with more details of the changes, here).

The WHO released and then redacted their statement on the Ebola response and WHO reforms. I preserved the original: http://t.co/N3mr4mQJ6e
— Caitlin Rivers (@cmyeaton) April 20, 2015

This new revision (copied below the original version) has some nice general changes, removal of contractions, removal of the numbering etc., but is weakened by the deletion of some other phrases leaving it feeling colder and covered by the fingerprints of bureaucracy - something that the first version felt like it was climbing above.

I'm disappointed. 

While I won't delete my tweets from yesterday, I would not have tweeted my respect for this version. Whomever you are that wrote that version - well done. I feel the retention of some of your key parts would have been better received by the world and they show you are indeed ready to move forward, acknowledging that everyone made and makes mistakes, or errors in judgement - that is to human - but that you own those and will seek to do better.

Original Statement 
At time of writing it was found here; some remove but humanising words are underlined

Joint statement on the Ebola response and WHO reforms

Statement by WHO Director-General, Deputy Director-General and Regional Directors, on the Ebola outbreak and response, and reforms to the work of WHO in outbreaks and humanitarian emergencies. 

1. The Ebola outbreak which started in Dec 2013 became a public health, humanitarian and socioeconomic crisis, with devastating impact on families, communities and affected countries. It also served as a reminder that the world, including WHO, is ill prepared for a large sustained disease outbreak.
2. We welcome the recommendations of the Special Session of the WHO Executive Board, in particular the proposed assessment of all aspects of the WHO response. Based on the lessons learnt, we commit ourselves to reforms that will enable WHO to play its rightful place in disease outbreaks, humanitarian emergencies and in global health security.
   
   What have we learned?
3. We have learned lessons of humility. We have seen that old diseases in new contexts consistently spring new surprises. We have taken serious note of the criticisms of the Organization that, inter alia, the initial WHO response was slow and insufficient, we were not aggressive in alerting the world, our surge capacity was limited, we did not work effectively in coordination with other partners, there were shortcomings in risk communications, and there were was confusion of roles and responsibilities at the three levels of the Organization.
4. We have learned lessons of fragility. We have seen that health gains –fewer child deaths, malaria coming under control, more women surviving child birth – are all too easily reversed, when built on fragile health systems, which are quickly overwhelmed and collapse in the face of an outbreak of this nature.
5. We have learned the importance of capacity. We can mount a highly effective response to small and medium-sized outbreaks, but when faced with an emergency of this scale, our current systems – national and international – simply have not coped.
6. We have learned lessons of community and culture. A significant obstacle to an effective response has been the inadequate engagement with affected communities and families. This is not simply about getting the right messages across; we must learn to listen if we want to be heard. We have learned the importance of respect for culture in promoting safe and respectful funeral and burial practices. Empowering communities must be an action, not a cliché.
7. We have learned lessons of solidarity. In a disease outbreak, all are at risk. We have learned that that the global surveillance and response system is only as strong as its weakest links, and in an increasingly globalised world, a disease threat in one country is a threat to us all. Shared vulnerability means shared responsibility and therefore requires sharing of resources, and sharing of information.
8. We have learned the challenges of coordination. We have learnt to recognise the strengths of others, and the need to work in partnership when we don’t have the capacity ourselves.
9. We have been reminded that market-based systems do not deliver on commodities for neglected diseases – endemic nor epidemic. But we have been encouraged by the desire of the scientific community, manufacturers and regulators to work together in this crisis to develop effective diagnostics, drugs and vaccines for Ebola.
10. Finally, we have learned the importance of communication – of communicating risks early, of communicating more clearly what is needed, and of involving communities and their leaders in the messaging.
    
    What must we do?
11. We will intensify our advocacy with national authorities to keep outbreak prevention and management at the top of national and global agendas.
12. We will develop the capacity to respond rapidly and effectively to disease outbreaks and humanitarian emergencies. This will require a directing and coordinating mechanism to bring together the world’s resources to mount a rapid and effective response. We commit to expanding our core staff working on diseases with outbreak potential and health emergencies so we will have at least [1,000] skilled staff always available at the three levels of WHO. We will also create surge capacity of teams of trained and certified staff so that we have at least [1000] additional staff available as a reserve force in the event of an emergency.
13. We will create a Global Health Emergency Workforce – combining the expertise of public health scientists, the clinical skills of doctors, nurses and other health workers, the management skills of logisticians and project managers, and the skills of social scientists, communication experts and community workers. This Global Health Emergency Workforce will be made up of teams of trained and certified responders who can available immediately. A key principle must be to build capacity in countries, with training and simulation exercises.
14. We will establish a Contingency Fund to enable WHO to respond more rapidly to disease outbreaks. We must ensure adequate resources – domestic and international – are available BEFORE the next outbreak. We welcome the proposal to create a pandemic financing facility.
15. We will change our way of working. Disease outbreaks demand a command and control approach – very different from the consensus building culture of most of our work in global public health. We commit to clarifying our roles and responsibilities within health emergencies, and organize ourselves to deliver on these roles. We will develop new systems for human resources, planning, logistics, information management and other areas that are so critically important in health emergencies.
16. We will establish partnerships with other organizations such as OCHA, UNICEF and WFP and other partners, to create a scalable operational response capacity for large scale disease outbreaks
17. We will strengthen the International Health Regulations – the international framework for preparedness, surveillance and response for disease outbreaks and other health threats. We commit to strengthening our capacity to assess, plan and implement preparedness and surveillance. We will scale up our support to countries to develop the minimum core capacities to implement the IHR. We will establish mechanisms for independent verification of national capacity to detect and respond to disease threats.
18. We will develop expertise in community engagement in outbreak preparedness and response. We will emphasise the importance of community systems strengthening and work with partners to develop multidisciplinary approaches to community engagement , informed by anthropology and other social sciences.
19. We will communicate better. We commit to provide information on disease outbreaks and other health emergencies as they occur, rapidly and transparently. We will strengthen our capacity for risk communications and for community engagement.
    
    We call on world leaders to take the following steps
20. First, take disease threats seriously. We don’t know when the next major outbreak will come or what will cause it. But history tells us it will come.
21. Second, remain vigilant. This Ebola outbreak is far from over, and we must sustain our support to the affected countries until the outbreak is over, in the face of increasing complacency and growing fatigue. We must continue to maintain a high level of surveillance. Ebola has demonstrated its capacity to spread – it may do so again.
22. Third, engage to re-establish the services, systems and infrastructure which have been devastated in Guinea, Liberia and Sierra Leone. This recovery must be country-led, community-based, and inclusive – engaging the many partners who have something to contribute – bilateral and multilateral partners, national and international NGOs, the faith community, and the private sector.
23. Fourth, focus on prevention. This means investing domestically and internationally in essential public health systems for preparedness, surveillance and response, which are fully integrated and aligned with efforts to strengthen health systems, and included in the scope of development assistance for health. It means working across sectors – health and agriculture in particular. These resources will be substantial, but as the well-known aphorism goes, prevention is better (and less costly) than cure.
24. Fifth, be transparent in reporting. Accurate and timely information is the basis for effective action. Speedy detection facilitates speedy response and prevents escalation.
25. Sixth, invest in research and development for the neglected diseases with outbreak potential – diagnostics, drugs, and vaccines. This will require innovative financing mechanisms, and public-private partnerships.
26. Finally, hold us to account. We commit ourselves to ensuring that WHO is reformed and well positioned to play its rightful role in disease outbreaks and in global health security generally. Some have said the world needs a new organization to be created. We agree, and we want WHO to be that organization.

New version

At the time of writing it was found here

WHO leadership statement on the Ebola response and WHO reforms

The Ebola outbreak that started in December 2013 became a public health, humanitarian and socioeconomic crisis with a devastating impact on families, communities and affected countries. It also served as a reminder that the world, including WHO, is ill-prepared for a large and sustained disease outbreak.

We, the Director-General, Deputy Director-General, and Regional Directors of WHO, are making this commitment of collective leadership to Member States and their peoples in line with recommendations made by the Special Session of the Executive Board on Ebola held in January 2015. We have taken note of the constructive criticisms of WHO’s performance and the lessons learned to ensure that WHO plays its rightful place in disease outbreaks, humanitarian emergencies and in global health security.

What have we learned?

We have learned that new diseases and old diseases in new contexts must be treated with humility and an ability to respond quickly to surprises. Greater surge capacity contributes to a flexible response.

We have learned lessons of fragility. We have seen that health gains – fewer child deaths, malaria coming under control, more women surviving child birth – are all too easily reversed, when built on fragile health systems, which are quickly overwhelmed and collapse in the face of an outbreak of this nature.

We have learned the importance of capacity. We can mount a highly effective response to small and medium-sized outbreaks, but when faced with an emergency of this scale, our current capacities and systems – national and international – simply have not coped.

We have learned lessons of community and culture. A significant obstacle to an effective response has been the inadequate engagement with affected communities and families. This is not simply about getting the right messages across; we must learn to listen if we want to be heard. We have learned the importance of respect for culture in promoting safe and respectful funeral and burial practices. Empowering communities must be an action, not a cliché.

We have learned lessons of solidarity. In a disease outbreak, all are at risk. We have learned that the global surveillance and response system is only as strong as its weakest links, and in an increasingly globalized world, a disease threat in one country is a threat to us all. Shared vulnerability means shared responsibility and therefore requires sharing of resources, and sharing of information.

We have learned the challenges of coordination. We have learnt to recognise the strengths of others, and the need to work in partnership when we do not have the capacity ourselves.

We have been reminded that market-based systems do not deliver on commodities for neglected diseases – endemic nor epidemic. Incentives are needed to encourage the development of new medical products for diseases that disproportionately affect the poor. The scientific community, the pharmaceutical industry, and regulators have come together in a collaborative effort to vastly compress the time needed to develop and approve Ebola vaccines, medicines, and rapid diagnostic tests. In future, this ad hoc emergency effort needs to be replaced by more routine procedures that are part of preparedness.

Finally, we have learned the importance of communication – of communicating risks early, of communicating more clearly what is needed, and of involving communities and their leaders in the messaging.

What must we do?

We will engage with national authorities and request them to keep outbreak prevention, preparedness and response management at the top of national and global agendas.

We will develop the capacity to respond rapidly and effectively to disease outbreaks and humanitarian emergencies. This will require a directing and coordinating mechanism to bring together the world’s resources to mount a rapid and effective response. We commit to expanding our core staff working on diseases with outbreak potential and health emergencies so we will have skilled staff always available at the three levels of WHO. We will also create surge capacity of teams of trained and certified staff so that we have a reserve force in the event of an emergency.

We will create a Global Health Emergency Workforce – combining the expertise of public health scientists, the clinical skills of doctors, nurses and other health workers, the management skills of logisticians and project managers, and the skills of social scientists, communication experts and community workers. This Global Health Emergency Workforce will be made up of teams of trained and certified responders who can be available immediately. A key principle must be to build capacity in countries, with training and simulation exercises.

We will establish a Contingency Fund to enable WHO to respond more rapidly to disease outbreaks. We must ensure adequate resources – domestic and international - are available before the next outbreak.

We recognize that emergency situations demand a command and control approach and we commit to seamless collaboration between headquarters, regional offices, and country offices. Better WHO systems for rapid staff deployments, data collection and reporting, expansion of laboratory services, logistics, and coordination were developed as the outbreak evolved. These systems will be institutionalized.

The massive international response revealed the unique strengths of multiple partners, including UN agencies. We will build on these partnerships, concentrating on capacities that are most critically needed under the demanding conditions of emergencies.

We will strengthen the International Health Regulations – the international framework for preparedness, surveillance and response for disease outbreaks and other health threats. We commit to strengthening our capacity to assess, plan and implement preparedness and surveillance measures. We will scale up our support to countries to develop the minimum core capacities to implement the IHR. We will establish mechanisms for independent verification of national capacity to detect and respond to disease threats.

We will develop expertise in community engagement in outbreak preparedness and response. We will emphasise the importance of community systems strengthening and work with partners to develop multidisciplinary approaches to community engagement , informed by anthropology and other social sciences.

We will communicate better. We commit to provide timely information on disease outbreaks and other health emergencies as they occur. We will strengthen our capacity for outbreak and risk communications.

We call on world leaders to take the following steps

First, take disease threats seriously. We do not know when the next major outbreak will come or what will cause it. But history tells us it will come. This means investing domestically and internationally in prevention and in essential public health systems for preparedness, surveillance and response, which are fully integrated and aligned with efforts to strengthen health systems, and included in the scope of development assistance for health.

Second, remain vigilant. This Ebola outbreak is far from over, and we must sustain our support to the affected countries until the outbreak is over, in the face of increasing complacency and growing fatigue. We must continue to maintain a high level of surveillance. Ebola has demonstrated its capacity to spread – it may do so again.

Third, engage to re-establish the services, systems and infrastructure which have been devastated in Guinea, Liberia and Sierra Leone. This recovery must be country-led, community-based, and inclusive – engaging the many partners who have something to contribute; including bilateral and multilateral partners, national and international NGOs, the faith community, and the private sector.

Fourth, be transparent in reporting. Accurate and timely information is the basis for effective action. Speedy detection facilitates speedy response and prevents escalation.

Fifth, invest in research and development for the neglected diseases with outbreak potential – diagnostics, drugs, and vaccines. This will require innovative financing mechanisms, and public-private partnerships.

This is our commitment; together we will ensure that WHO is reformed and well positioned to play its rightful role in disease outbreaks, humanitarian emergencies and in global health security.