Monday, 15 September 2014

Happy 2nd birthday Middle East respiratory syndrome coronavirus (MERS-CoV)...

Its been 2-years since Prof. Ali Mohamed Zaki sent his email to ProMED notifying them of a novel coronavirus. That email was published 20-Sept 2012.[1] 

A year ago we had 138 cases and 58 deaths. Today we have 856 cases with perhaps 306 fatal (36%).

I won't rehash what I said a year ago - I invite you to check that out over at the 1st birthday post.[2]

Suffice to say the past year has been, to my mind anyway, mostly about:

  • Camels
  • High level job "shuffling"
  • Controversial parallel publications
  • Very problematic infection prevention and control issues.
The latter leading to the relatively huge number of MERS-CoV detections and deaths in Saudi Arabia and to some exported detections and cases. The one constant over both years has been that the MERS-CoV is a pitiful spreader among humans. MERS-CoV is nonetheless a virus that is very capable of inducing fatal outcomes, especially among older males with underlying diseases.

Has MERS-CoV gone away? No. Of course it hasn't. MERS has, mostly. That's the disease, not the virus. For now anyway MERS cases are sporadic, although still geographically widespread. 

MERS cases fell to zero cases per week for a number of weeks this year following containment of the Jeddah-2014 outbreak. Nonetheless, this is a virus of camels that seems to  spread, rarely, to humans and when in us, it has not been in any rush to mutate into the pandemic SARS-like threat many once worried about. 

Camels are where this virus likely remains. And there have been no signs that that has in any way changed. The latest information suggests camels have been harbouring MERS-CoV for at least 30-years.[3] This, as with a great deal of the research to date, is knowledge gained mostly thanks to the efforts of international research teams and their funding

So Happy 2nd Birthday you opportunistic, spiky little killer. I'm once again wishing Dr Zaki well and congratulating him on co-parenting the birth of this novel coronavirus. This year I also wish Prof. Ziad Memish well and congratulate him on seeing the infant virus through to toddler age.

Oh, and 2-years on, I still see no sign that the contentious patenting issues were any sort of hindrance to diagnostics or actual research. Just sayin'.


  2. Happy 1st birthday Middle East respiratory syndrome coronavirus (MERS-CoV)
  3. MERS Coronavirus Neutralizing Antibodies in Camels, Eastern Africa, 1983–1997

Sunday, 14 September 2014

The proportion of fatal cases (PFC)...

This is excerpted and altered a little, from a more influenza A(H7N9) virus slanted article to be found here. But I think it deserves its own page.

In July 2013 I coined a term on VDU to avoid the use of the term Case Fatality Ratio/Rate/Risk (CFR). 

My term was the Proportion of Fatal Cases (PFC). I use the term on VDU and have published it an article.[1] I have no expectations that anyone else will use it although I notice it made an appearance in a HeathMap story[2] by Maia Majumder.

The PFC is a percentage calculated as the currently known number of fatalities divided by the number of total lab-confirmed cases including fatalities, regardless of whether surviving cases are inpatients (hospitalized) or outpatients.

The PFC is just a number - it's not meant to imply that every case that ever happened is included - it never could. It does not account for those cases who will die later on, either directly or indirectly, as a result of their infection but who may be alive at the time of calculation. 

The PFC is a snapshot to be used before an outbreak is done and dusted. It is meant as a guide to what is happening right now using the data we can get our hands on. Sometimes that means lots of data and sometimes they are very limited or just plain behind closed doors.

The CFR makes use of the number of recovered cases in its denominator.[3] So it's important to know survivor numbers. As suggested above, this requires that all the people who will recover from their infection, have recovered (and been discharged) from their infection. 

Using the CFR early in an emerging virus/disease outbreak, when what usually brings in outbreak to our attention is death, is great for selling papers, but not helpful realistic in a bigger picture sense. 

The CFR is most useful at the end of an epidemic/pandemic, but not so much when data-in-hand is poor during the early days of many outbreak. 

Of course, some will take a PFC and multiply it by the world's population as an estimate of how many are going to die if the virus reaches pandemic levels. That's not helpful or accurate. Just accept it as that snapshot of what's happening now.

  1. J. P. Dudley and I. M. Mackay. Age-Specific and Sex-Specific Morbidity and Mortality from Avian Influenza A(H7N9). J. Clin. Virol. 2013. Nov;58(3):568-70. ePub Sept.

Saturday, 13 September 2014

The wind beneath my Ebola virus....

Only a couple of weeks ago the report in Science presented 99 genomes representing some of the thousands of those circulating in Sierra Leone this year.[1] I say thousands because each infected person has a range of subtley different viral variants among the billions of viruses per millilitre of blood that all compete to be the champion. The words "mutant" and "ebolavirus" are now hard to avoid. And of course as soon as you talk mutations, you can only see one endgame - a virus that is easily transmissible and turns us all into zombies. spreads across the world in a pandemic and kills as many as 80% of those it infects. Yes, its seems the proportion of fatal cases (PFC) in West Africa may not be as simply calculated as most of us were thinking these past months. When we take into account that Ebola virus disease deaths occur in people that were part of a case tally days earlier (if they were counted of course) when the total case numbers were smaller, the PFC inflates. How much, we don't really know.

And so the story of mutants was brought full circle today thanks to Dr. Michael T. Osterholm. In a very nicely written piece for the New York Times,[2] Dr. Osterholm, ventured behind the scenes to crack the door into the world of whispered discussions, shadowy frappé meetings by chino and beige blazer-wearing figures, many of whom were men with with thinning hair. Yes, he found where the real virologists hang out and what were they discussing at length? Why they were talking about how soon it would be until Zaire ebolavirus was going to mutate and become an airborne killer virus identifiable only through watching big wall-mounted LCD screens as they are rendered in red because of the fusion of rapidly growing dots, spreading across a map of a world filling rapidly with infected hosts. Or red dots. Or something. Okay, some of that was from me.

Only problem is, I think he may have entered the tinfoil hat room next door to the (but very similarly attired) room full of virologists. Maybe not. Hard to tell sometimes. But seriously.

For sure, a virus changes over time. It will respond to all sorts of pressures by changing its genetic sequence and sometimes that results in changes to the proteins that make it's structures and enzymes. Sometimes it changes back as pressures go away and more efficient means to replicate return. Keep in mind ebolaviruses didn't come down in the last shower. They are viruses that are happy in their own envelopes...and natural host(s). But these genetic changes then can impact on how the viral "bits" assemble and release from the cell and perhaps on how the virus causes disease, where it replicates in the body, how it interferes with the immune system's attempts to interfere with it and so on. A virus doesn't "think" about this of course. It doesn't plan to do the nastiest thing to us that we can imagine. These changes happen because, in a host with many subtley different viral variants vying for supremacy, the virus with the mutation(s) that allow it to get out from under some sort of controlling pressure, wins; it will thrive and pass on.

A virus may make more of these changes while it is "settling in" to a new animal host species. There can be all sorts of new pressures to try and avoid or adapt to. Remember, ebolaviruses seem to naturally infect bats, not us, and in bats the infection does not seem to cause a whole lot of disease. Of course we don't know a whole lot about how bats spread virus among themselves. The theory then goes that humans or other forest animals including chimpanzees, gorillas, porcupines and antelopes may eat the bats or bat/virus-contaminated fruit. We, and those animals, do get sick.

What is much less of a sure thing, a sizable knowledge gap you might call it, is whether an ebolavirus would actually be under any pressure at all to change in a way that would make it more stable in dried droplets, shed in higher concentrations from the upper respiratory tract or trigger it to start adding more coughing or sneezing in its Ebola virus disease, each and all of which may aid propulsion of droplets which must dry down and linger while remaining infectious, for an ebolavirus to become "airborne". I think we understand it doesn't "know" that these would be better spreading outcomes and that it already spreads very well. To date that has never been found to happen naturally in the spread of Ebola virus disease in humans. Which is some kind of significant considering it does not take a lot of virus to start an infection though direct contact and there have been non-human primate transmission chains in the forests. Each of those changes might happen by accident. But really, to be airborne, these changes would need to co-occur and also co-occur without any trade-offs that meant the 'new airborne virus' was negatively impact in some other area. You see we do know that under laboratory conditions, with plenty of virus and a closed space with a lot of aerosol (possibly wet droplets), an Ebola virus can be forced to infect non-human primates. I've written about that previously.[3] And yet even when it was sought, no sign of such airborne infection could be found to occur naturally among humans. Direct. Contact. 

So I think it's a stretch to spend so many words on the chance that an airborne virus will emerge rather than one that causes more bleeding, or less diarrhoea, or more vomiting, or more shedding in sweat, more rash, more hiccups etc. Many things could result from these changes. We know next to nothing about the ones we've recorded from the 99 genomes. But why this really quite complex outcome of air travel, instead of many/any others? But hey, now we can talk about this aspect some more, so good one Dr O!

Dr Osterholm did hit some other nails flush with the timber though. West Africa needs fewer promises to defeat Ebola virus and more plans that include actual rapid mobilization and on the ground experienced leadership to make inroads into getting beds for sick people and tracing contacts. Two key items on a long list of things to do better (in my opinion).

Thankfully some promising signs are appearing. The scope of this outbreak has now been guesstimated - 20k-100k cases.[4,5,6,7] I list this range rather than extending it to much higher levels [8] because I do still have hope that things will improve and interventions will turn the exponential case growth curves away from the sky and back to the horizon, sooner rather than before entire nations are destroyed. Because that's what is coming without successful intervention.

Money is being freed up and arriving from all over and more resources are slowly moving in to the region. Resources needed just to keep the people safe who have come from all over the world, including the nations of Africa, to care for the overwhelming numbers of sick and sickening people. Not to mention the money needed to prevent more infections. More specific and insistent pleas for defined numbers of healthcare professionals are also being broadcast. Drugs and vaccines are closer than they have ever been to use in humans. They may be our only hope to stop this virus.

If the many thousands of people predicted to die from a virus that is killing 4 in 5 confirmed cases (see the Medicins Sans Frontieres tweet below) is not enough reason for stopping the spread of Ebola virus, then stopping this particular evolving variant before it does change into something worse or more ingrained to the communities all over Africa and beyond, really is. While it may not make the changes necessary for it to go airborne, it has shown signs of rapid adaptation and that was relatively early in what is going to be a very long chain of human-to-human-to-human-to-human... transmission. Each person allowing the virus to adapt further if that's what it needs to do 

Such a long transmission chain, from 1 animal>human infection, has never been recorded before and so we are indeed in new territory when it comes to the ebolaviruses. For now at least, the Ebola virus in 5 countries in and around West Africa has the upper hand. This tiny self-assembling unthinking, thing is totally dependent on our cells to replicate itself - and we are not doing enough to starve it of those cells. 

It clearly doesn't "need" to be airborne to spread efficiently.


Saturday, 6 September 2014

Case number changes between Ebola virus disease reports...

This is one of my favourite charts for following the Ebola virus disease outbreak in West Africa because it shows how things are changing from report to report. 

It plots the total number of suspected, probable and laboratory-confirmed cases between reports - which is a measure of change over time that is not cumulative.

That's not to say that understanding this chart is easy for with everything, what you take away from it may be heavily influenced by your own perspective and your background in reading graphs. I have written something about how to read some of the graphs on my blog here, which may be helpful too.

Uses World Health Organization data up to and including the Situation Report from the 5th-Sept, 2014.
Click on chart to enlarge.
I've marked up the last three periods between reports to highlight that the time changes differently. You can see this for yourself if you look carefully at the horizontal or "x" axis (the one that has the dates) and look at where each dot lines up with its date. Some are further apart than others. 

You can also mouse over the dots on the interactive version of the graph here. That will tell you the dates. THe subtraction is up to you though!

The lines joining the dots here suggest what is happening between the WHO Reports, but the line do not actually use any real collected values...because we don't have them to plot. 

Technically, a bar graph would be more accurate, but I find a line graph easier to read at a glance. So do remember - we don't know what is happening between those dots. We're just presuming it.

Friday, 5 September 2014

Editor's Note #20: Tweepidemiology...

Followers of my @MackayIM Twitter account (and this blog which gets promoted through it) since I started tweeting. It shows the cumulative rise and rise of followers and the relationship of rate of that rise to a very active period of infectious disease epidemics over the past 18-months or so.
Click on the graph to enlarge

While its hard to separate whether I pick up followers because of delivery of specific content or because as you pick up followers, they help spread the word and you pick up more followers, to simple old me this cumulative graph looks like MERS-CoV and the West African Ebola virus disease outbreaks have driven people to seek information. And sometimes they've done me the honour of following me on Twitter as I seek to understand what's going on as well. I'm constantly amazed at that, let me assure you.

I thought it worth having a look at the Tweepidemiology of my Twitter account. That is, the epidemiology of my Twitter followers - a bit of a long bow - but you follow me because I talk about infectious disease outbreaks and stuff so, given that I like my new word, I'm keeping with it!

I paid Twitter Counter to get my Twitter data and plotted it in Excel and tidied it using Illustrator and here it is. 

I started Tweeting a little after I started blogging - this Twitter thing is for the young people and their constant need to take selfies and update the world on their lives

Despite VDU blog posts on the emergence of influenza A(H7N9) virus in China dating back further in time, I came to Twitter well after H7N9's Wave 1 was engaged. So the slow burn could have been due to that or just because no-one knew me or that I could generally be trusted and generally don't spout drivel. 


So there ya go - Tweepidemiology as a way of looking at when and perhaps why one gains followers through Social Media when used to engage and try and help people understand what's happening with new or emerging viruses and diseases . Perhaps I should check what happens when I post photos of my cat too.

Sunday, 31 August 2014

Ebola: Blood, sweat and tears...

This post follows up the recent one on convalescent semen being able to harbour infectious Ebola virus (EBOV; although I am not aware of any infection resulting from this route of transmission there has been at least one report for Marburg virus [4]).

I thought I'd give the same treatment to tears and sweat which are also fluids intermittently listed as possible sources of EBOV infection for humans. Some examples of the scientific literature which support the risk messaging, follow.


I think we are all pretty clear that the blood of an advanced case of Ebola virus disease (EVD) is heavily laden with virus and is the most serious of the risk factors for acquiring infection by an ebolavirus.

Viral loads (amount of virus in the sample) in blood can be above 106-108 plaque forming units or copies (pfu; a measure of infectious virus present using a lab test that measure the impact of virus on infected cells; copies measure viral genome and cannot prove infectious virus is present) per millilitre of blood in acute phase disease patients and non-human primates.[5,6]


There is not a lot on sweat containing signs of an ebolavirus.
  • Bausch and colleagues found no trace of EBOV in a single acute sweat sample.[1]
  • Jaax and colleagues found that in experimentally infected non-human primates (NHPs; rhesus macaques), that connective tissues next to hair follicles and sweat glands in the skin as well as the cells lining ducts of glands in the skin were sometimes positive for EBOV antigens (proteins).[2]
  • Davis and colleagues infected NHPs (African green monkeys) and found signs of EBOV antigens in the cells lining the sweat gland ducts and in cells in the connective tissues next to hair follicles, but no virus particles by electron microscopy.[3]
  • Zaki and colleagues found heavy signs of EBOV antigens (proteins) in the tissues around the sweat glands, but rarely also within sweat glands and ducts.[8] No virus particles were seen in the sweat glands or ducts when examined by electron microscopy.

There is also very little I have found on this one.

  • Bausch and colleagues found EBOV RNA in tears from 1 sample, but no infectious virus could be isolated.[1]
  • Jaax and colleagues found some signs of virus in macrophages in the ciliary body of the eye of experimentally infected NHPs
  • Bausch and colleagues found infectious EBOV in 1 of 12 acute saliva samples (from 10 patients; none from 4 convalescent samples) and EBOV RNA in 8 of 12 (67%) of acute samples (none from convalescent samples).[1] RT-PCR positivity was significantly associated with fatal outcome.
  • Formenty and colleagues found EBOV antigens and EBOV RNA in oral fluids from fatal cases and those who survived infection.[7]

Saturday, 30 August 2014

The fifth I give you...[UPDATED]

According to it's Minister of Health, Awa Marie Coll Seck[1,2], a case of Ebola virus disease (EVD) has been imported from Guinea and it is confirmed by testing at the World Health Organization's collaboration Centre, the Pasteur Institute in Dakar.

Interesting that this occurred one week after Senegal closed its borders (again) with Guinea.[3,4] The infected 21-year old Guinean student travelled on 21-August to Dakar. On the 23rd he presented to a hospital but did not admit to being in contact with known EVD cases; Guinea issued an alert that a person with EVD contact has escaped surveillance 27-Aug; Senegal closed its borders around 22-August.[5,6,7,8].
[WHO Disease Outbreak News places his movements ahead of the closure of the border, arriving in Senegal 20-Aug [8]]

These borders are leaky and so the effect of "closure" essentially hinders aid, trade and economy (all very important to the region, especially right now) but very clearly does may not stop the spread of human hosts-as we have seen here

Humans are the variable in outbreaks. 

They behave differently each time. 

They respond differently each time. 

This is why no two outbreaks are identical. 

It's why you're a mug to assume this outbreak will be like the last outbreak.

While it looks like this is now a case study in why closing a border is ineffective, I maintain a position that border closures can't contain infectious disease. And please, do not point me to "temperature measurement" as a way to ensure capture of infected individuals. You could easily be harbouring an infection that does not yet express the symptom of fever. 

Click on image to enlarge. 
Graphic lifted from a great CNN video narrated by
Dr Sanjay Gupta. The video describes an example of
contact tracing and its importance to the fight
to contain EVD.[2] 

The contact tracing starts in Senegal now. A 42-day clock starts for the country and a signs and symptoms watch continues on all this case's contacts for 21-days.


Thursday, 28 August 2014

MERS-CoV around the house-yes, it does transmit at home

Click on graph to enlarge.
Some Middle East respiratory syndrome coronavirus (MERS-CoV) questions remain stubbornly unanswered even after two and a half years.

Today comes a study from Prof Christian Drosten and colleagues, including Prof Ziad Memish, released by the New England Journal of Medicine.[1] This study takes a look at MERS-CoV infection among the contacts of MERS cases.

We already know that asymptomatic or "silent" MERS-CoV infections are not rare. At least 17% of detections of this virus have occurred in people with no overt signs or reported symptoms of disease. That's not to say that they didn't have a slightly raised temperature, headache, sniffle or something very mild that got overlooked or forgotten, but nothing noted or noteworthy. I'd love to see a study on asymptomatic MERS-CoV infected people that looked into fine detail signs and symptoms by the way-that might tell a nice little story about "silent" infections.

This new study looks at the contacts of infected cases from 26 different households, each with a single confirmed MERS-CoV infected case, with MERS. These households provided throat swabs from 280 contacts and antibody test results on at least 1 sample (only 44 permitted a second voluntary blood sample be taken-a shame) from the 280 contacts as well.

Some interesting findings included:

  • Median age of cases (65.4% male) was 55-years
  • Median age of contacts (52% male) was 29-years
  • Cases 7 household contacts (2.5%) were viral RNA-positive (RT-PCR) within 2-weeks of the index patient's illness onset. Similar to what PCR-based studies conducted previously have yielded.
  • 5 household contacts (1.7%) were considered antibody positive after a series of different tests were used. 3 were positive between 2-3 weeks after the index case's onset, and 1 each before or after that period. 
  • some indication that neutralizing antibodies against MERS-CoV might be low level and short lived in mild or asymptomatic infections and that previous antibody studies may have missed some cases if the took blood too long after a mild infection
Overall, 12 (4%) contacts acquired MERS-CoV infection from an index case, across 6 of 26 households (23.1%). 

Among others, one question I'd like answered is whether symptomatic cases being kept in home isolation, which was occurring during the Jeddah-2104 outbreak when they don't need hospital-based supportive care, is the best option for stopping transmission? We don't know whether mild or silent infections can transmit virus, which remains another important question. While 4% seems like a small proportion, it's big enough to perhaps explain some of the sporadic case occurrences. Also, we should be mindful that MERS-CoV infection is associated with the death of a third of the people it infects. I'd want to be pretty sure I wasn't letting a house-bound shedding mild/silent person spread MERS-CoV to a visiting old uncle with a co-morbidity.

  2. If this is what MERS-CoV detections look like with more testing...what is the "normal" community level of virus?? [UPDATED]
  3. Guidelines for home isolation related to MERS Corona Virus infections | May 2014

Monday, 25 August 2014

The battle of Ebola gains a second front...the Democratic Republic of Congo (DRC; formerly Zaire) [UPDATE #3]

So there are three reasons for this post. 
  • It may be a little while before we get solid confirmed information from the DRC and I think maps are useful for those of us who are ignorant of where countries live! [See below for update from WHO]
  • I'm looking for a quick post so I can move the previous post's grisly pictures down the page!
  • Mike Reid (see comments below; many thanks) brought to my attention that the range of the hammer-headed bat (Hypsignathus monstrosus; [5]) overlays the current ebolavirus outbreak areas strikingly well. I lifted that range graphic and (imperfectly, in pink) overlaid it onto my map - et voila!
Data for the hammer head bat's (Hypsignathus monstrosus) range come from The International Union for Conservation of Nature (IUCN) Red List of Threatened Species. I adapted the graphic for VDU from Wikipedia [3]
An 24-Aug report quoted the Minster for Heath, Felix Kabange Numbi.[2] This latest outbreak occurs in a country that was the site of the first (known) outbreak of a virus of species Zaire ebolavirus (called Ebola virus [1] or EBOV), and which has had six other battles with Ebola virus disease (EVD).

One of the two viruses was reported to have been genotyped as a member of the species Sudan ebolavirus (SUDV) and the second was a "mixed" infection of SUDV and an EBOV.[2] A mixed natural infection of a human would be very...unheard of. Can't really say much more though, until we get this all clarified. 

A 26-Aug WHO-AFRO update noted that the index case, a woman from Ikanamongo village, died 11-Aug sometime after butchering a bush animal.[6] 24 suspected cases of haemorrhagic fever occurred between 28-Jul and 18-Aug. 

The latest updates define that the outbreak is solely due to viruses from the species Zaire ebolavirus.[7,8,9] The EBOV viral variants share 99% nucleotide identity with the Kikwit lineage of viruses from this same species (not "strain"). Put simply, this is the evidence needed to be able to state that the two concurrent EVD outbreaks (indicated in the map above as distinct events), are indeed due to genetically distinct viral variants of Zaire ebolavirus and are not related outbreaks. 

For more on naming ebolaviruses - check out my earlier post "Behind the naming of ebolaviruses".[10]

This latest outbreak was previously and relatively quickly (too quickly? Perhaps a message in there for all of us) described by the World Health Organization as being due to gastroenteritis with haemorrhaging...

...but subsequently we learn today that...

The outbreaks share at least one common potential animal vector range. This is one of three bat species often pointed to as a possible natural host for ebolaviruses.

Since this is not the first time concurrent outbreaks of ebolaviruses have occurred, I was wondering about seasonal factors and whether they attract or affect bats. This new information adds another piece of of the puzzle.


Sunday, 24 August 2014

Fake/wrong Ebola virus disease images...

As if there isn't enough misery in the world that we need add false imagery to the mix.

Fake or hoax or just plain misunderstood images purporting to be from cases of Ebola virus disease are everywhere at the moment. The ones below are images I see regularly in the #ebola Twitter stream. 

I had once before found the real image of the first picture using a reveres image searhc on Tineye or Google's image search, but lost it until I recently downloaded my Twitter history and did a manual search for the words I thought I'd used. Bazinga! 

I'll add to this page as I find references for other fraudulent imagery. Feel free to send me other fake Ebola-related images (with the original source) and please use this page to throw at people using these images.

While I suspect much of this is just retweteed out of a lack of information, I'd ask that people check before they propagate this sort of stuff. It may dissuade others in the affected regions from seeking medical attention if they think they have been exposed because "If I don't look like that then I can't have an Ebola virus infection!"

Figure 1. This is from a patient with which has haemorrhagic
bullae simulating purpura fulminans...whopping great blood
blisters and tissues that have been bled into. Image comes
from a case of leukaemia cutis published in the Indian Journal
of Dermatology, Venereology and Leprology in 2010 by
Misri and colleagues

Figure 2. This is from a boy with smallpox disease. It can be found 

Large hemorrhage on arm of dengue patient
Figure 3. This is bleeding under the skin in a patient with dengue
hemorrhagic fever. The image can be found on the National Institute
of Health's National Institute (NIH) of Allergy and Infectious
Diseases (NIAID) website
Figure 4. This may be an allergic reaction, possibly 
to contact with poison ivy. I'm not as sure about the source
of this one. Some possible places include:


Figure 5. I can only find ebolavirus-related results for this. 
If anyone can confirm or debunk it as being a valid EVD image, I'd 
be grateful if you could tell me.