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.

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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.

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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.

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MERS-CoV snapdate on canaries...

MERS-CoV detections among healthcare workers (HCWs)

HCWs are akin to the canary in the coal mine - when HCWs get sick with a particular bug, this can signal that the bug may well be more active in the the wider community. 

This graph looks at the canaries and suggest that there has been a relatively long period in which they have been getting infected.

Healthcare workers positive for MERS-CoV over time.
Some reported or hypothesized clusters and outbreaks are flagged.
Click on image to enlarge.

A quick look at my database shows that most of the MERS-CoV-positive HCWs reported since October have been from Riyadh in Ar Riyadh region and Taif in Makkah region. 

Just before that, in early September, there were 2 HCWs from Jubail in the Ash Sharqiyah (eastern) region. 

If we look at the new time-based occurrence heatmap I have on my MERS-CoV static page here, the recent group of HCWs come from the areas with most cases. No big surprise there. Perhaps more surprising is why these HCWs are, presumably, still acquiring there infection in hospital settings given eh attention that infection prevention and control practices had, especially (before?) during and after the Jeddah outbreak last year.

A recent paper from Profs Drosten and Memish speaks to this topic of infection control and hospital spread of MERS-CoV a little.[1] 

It reports finding a 40-year old female (40F) nurse who, despite MERS-CoV being such a wimpy transmitter between humans, became infected after attending an infected patient. 40F did not perform any aerosol-generating procedures  but also wore only a surgical mask and gloves - it reads as though she was not fully protected against droplet, and certainly not against airborne, exposure. 

The 40F HCW then went on to shed virus for a 42-day period as determined by MERS-CoV specific RT-PCR. She was not ill during this time. Hard to contain much?

So with all that in mind, it's no longer hard to imagine how spread of MERS-CoV virus occurs within, around and between hospital settings. Also helps to explain how some of the new cases might seem strange - if not testing for subclinical or asymptomatic cases as a routine. I recall that in Saudi Arabia routine testing of milder cases is not occurring, but I cannot find a source for that recollection just now so I stand to be corrected (please send if you know if a reference that alludes to that).

A couple of quick questions spring to mind:

1. Just how widespread is this lengthy shedding period?
2. What does this say about how mild a virus MERS-CoV is when comorbidities are not a factor?
3. What role do genetics play in the host's containment and clearance of MERS-CoV infection?

Heatmap of MERS-CoV detection by date and region
within the Kingdom of Saudi Arabia
Click on image to enlarge.

Reference..

1. A Case of Long-term Excretion and Subclinical Infection With Middle East Respiratory Syndrome Coronavirus in a Healthcare Worker. Manal Al-Gethamy, Victor M. Corman, Raheela Hussain, Jaffar A. Al-Tawfiq, Christian Drosten and Ziad A. Memish.
   http://cid.oxfordjournals.org/content/early/2015/01/01/cid.ciu1135.long

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MERS-CoV snapdate...

MERS-CoV detections by month and year

As can be seen from the graph below, the peaks of MERS-CoV detection have been driven by humans and their infection prevention and control issues - but what maintains the virus in between those lapses? 

It seems clear that MERS-CoV is entrenched among camels in the Middle East and Africa but how is it getting to humans, and how is it dong that in such small numbers over such a wide area? These have been questions for 148 weeks. 

It's a good thing this infection transmits so poorly between humans.

Click on image to enlarge.

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Case->outbreak->epidemic->publication->learn a lesson...repeat

The global cumulative curve of suspect+probable+confirmed
cases EVD cases (orange) , suspect+probable+confirmed
EVD deaths (red) and the confirmed cases (yellow dots)
Updated from last WHO data posted 10JAN2015 AEST.
Click on image to enlarge.

When looking at the PubMed database search results for 'ebola', one can have no doubt that something big must have happened lately to drive such a massive number of science doers and writers to their keyboards. 

And of course something did - the world's largest, most widespread, multinational and longest running epidemic of Ebola virus disease (EVD) which roared through Guinea, Sierra Leone and Liberia. At the end of 2014 there were 20,000 cases and 8,000 fatalities - and those were just the cases we have seen added to official lists and made public.

A tally downloaded from the PubMed search engine
based on numbers returned using the search term 'ebola'.
Click on graph to enlarge.

The adjacent image shows what the US National Library of Medicine's search engine generates when one searches for 'ebola'. The search engine, called PubMed because it makes the MEDLINE database public (MEDLINE being the Medical Literature Analysis and Retrieval System Online, or MEDLARS Online), lists many of the world's life science and biomedical publications that meet the PubMed standards; currently >24,000,000 citations. In 2014, a lot was written about EVD.

While a lot of the 'ebola' publications in 2014 were commentaries and a lot of reviews that mostly presented the same information, these were necessary to feed many different groups of readers and specialities hungering for background on EVD and the ebolaviruses and how these related to them and their roles, patients and lives. 

I had cause to scan the literature on a daily basis for a few weeks and was particularly impressed with the New England Journal of Medicine's clinical papers and the BMJ's summaries and updates. Of course Science/Sciencexpress and Nature had some beautifully informative articles as well - delving into the humanity behind the numbers and seeking answers to questions we were all asking. I thought PLOS Current Outbreaks (although I'll never enjoy reading that layout), Lancet, Lancet Infectious Diseases and Morbidity and Mortality Weekly Report also stood out in 2014. 

Some of these articles came out very quickly and many were available without the need to breach a paywall. But some of the research...I can't help but wonder how many lives could have been saved if studies detailing and reinforcing the apparent benefits to survival from the aggressive use of intravenous fluids and electrolytes could have come out sooner-through whatever venue. What if we'd talked about, researched or actually published better personal protective gear designs earlier? Imagine if the world had registered that Ebola virus seemed to be in the region years ago, when research papers suggested it. Would any of this knowledge have saved more lives? Who knows? Would the focus on what needed to be delivered to West Africa have changed because of earlier dissemination of need? Would more point of care chemistry instruments have been prioritised? Would the urgency about the need for more healthcare workers have been stepped up if more specific examples of why they were needed were out there for our leaders to be briefed on? Probably unanswerable questions.

Why can't humans ever seem to learn enough to prevent the event sneaking up and whacking us senseless? Why is it always after the event that the light dawns and processes are created for 'next time'?

There will be many more publications to come in 2015, spinning out of this epidemic and the events yet to unravel. Hopefully they will create enough memory for the world to be better prepared for next time. Prepared for a little...uooh - goober fish...

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