Monday, 17 November 2014

Ebola testing: 48-72 hours for a negative to turn positive

Currently, some fraction of the people who present very early after they may have been infected by Ebola virus for testing, return a negative result. This is probably a rare event because the majority of cases arrive for care with Ebola virus disease (EVD) already well underway.

The latest Centers for Disease Control and Prevention (CDC) guidance in these instances is to wait (48 to) 72 hours and see if the patient remains ill, or becomes more unwell. If they do either of these, a second test is performed.[1] If the suspect case recovers from illness, no repeated testing is indicated. 

The test we rely on to confirm a clinically suspected EVD case is called a reverse transcriptase polymerase chain reaction (RT-PCR). RT-PCR is a technique designed to  seek out a tiny but very specific region of the Ebola virus's RNA genome, copy it into DNA then amplify those DNA copies a billion-fold by making more copies. Somewhere during that exponential amplification process, the technology of the day (currently fluorescence detection but formerly agarose gel detection, radiation and chemiluminescence) allows us to identify that the specific DNA we seek is appearing above an arbitrary threshold...we have a positive test result for Ebola virus. 

RT-PCR is a very sensitive technique. It was not that long ago - the 80s, not that long for some of us anyway - that clinicians and scientists were complaining that PCR methods were too sensitive. This was in large part because PCR was too successful at finding infectious agents where, and when, they had not been previously found. Change to dogma was in the wind. Fast forward to today and now we're lamenting that PCR isn't always sensitive enough. Very early on after acquiring what we later know to be a true infection, even exquisitely sensitive PCR methods can fail to detect those earliest of viruses while they are struggling to gain a foothold in our cells and replicate themselves to levels that outstrip our immune system's capacity to contain. Whether this is because the virus is hidden away in organs during its early replication or whether too few circulating viruses yet exist to surpass the necessary threshold of the RT-PCR assay's sensitivity at these early stages is unclear.

EVD patients who are not yet showing signs and symptoms of disease may present early for testing and care because they they are healthcare workers with a suspected or known exposure, or they may be the contact of a known EVD case or infected animal being tested early on to exclude infection. But as we have seen and read anecdotally, that first test can sometimes be negative; not due to inhibition of the RT-PCR (which can also happen, just not so much with today's purification methods) nor because they are truly uninfected, but simply because we're testing too early. These are examples of false negative results.

For the past few weeks I have been trying to find he evidence that underpins why the world chooses to use a 48-72 hour window in its guidelines. I've been asking a lot of people-and I thank those who replied. Tonight the very diligent and extremely tolerant folks at the World Health Organization got back to me with a quote from Dr Pierre Formenty, team leader Emerging and Dangerous Pathogens. A hard man to get hold of sometimes-as you might imagine. He said (lightly edited)...
There is at least one documented case during an outbreak in Africa; a contact with fever = a suspect case; he was negative at day 1 with RT-PCR (CDC Lab) and was found positive at day 3 (when retested).
So the 48-72 hours come from this incident. We want to be on the safe side and limit the number of false negative that are inevitable with any test.
And so there you have it. If anyone has anything further to add to this story, I'd be most happy put it here.


Sunday, 2 November 2014

Influenza A(H7N9) virus: detection numbers and graphs...

This is a static page that will house my graphs of influenza A(H7N9) virus ("H7N9) numbers produced by the various Ministries of Health for the provinces and municipalities of China, the World Health Organization and FluTrackers.

They may take me a little while to get back up-to-date in this new format so stay with me. I will Tweet each update as I do for MERS-CoV and Ebola virus updates.

There is also an accompanying map page which for now is located here.

Uses latest WHO data  posted:

Uses latest WHO data posted:

  • The graphs above, as with all on VDU, are made for general interest only. They are also freely available for anyone's use, just cite the page and me please. The data can be downloaded by clicking on the "Download" link at the bottom-right of each dashboard. It may be that I have misinterpreted the language in the reports (sometimes a little tricky to wade through) or miscalculated some totals based on the way data have been presented.
  • In any outbreak, epidemic or pandemic caused by a know or emerging pathogen, the numbers presented publicly, and used in these graphs, are expected to represent only a fraction of all the cases that have and are occurring. This is just the nature of the imperfect biological'ness of these events.
  • I am only able to plot what is publicly available-you could do this too. No secret associations or back-room deals provide me with these data.

Friday, 31 October 2014

The bad the worse and the over-interpreted...

EVD case numbers between WHO reports. 
The World Health Organization (WHO) Ebola virus disease (EVD)case numbers that came out on 29-Oct were pretty big (see graph on the left). As if there weren't already enough new cases and deaths every 2-5 days, now there is this bolus of 3,562 cases added to the total. And a net change in deaths of -2? What the heck?  

Let's see if we can add some context.

According to a number of past WHO reports, a lot of effort has been going in to trying to collect data more effectively including improving the linkage of lab results to cases, cases to deaths, lab data to deaths and probably a million other things. 

Dr Bruce Aylward
In the previous Roadmap SitRep and Roadmap update, the Liberian numbers did not move - they even had the same date. That was new and it was concerning because it suggested that reporting had been stopped or collapsed entirely. However this new large download of cases is in some way good news because it suggests reporting is working and the systems and processes are coping - although undoubtedly still stressed - again. 

The thing to be aware of is that these are not cases that have all been detected or all occurred since the last report 5 days previously. According to Dr Bruce Aylward, WHO Assistant Director-General, Polio and Emergencies, during a preceding media conference (and my thanks Martin Enserink for asking the important question; underlining is mine)..

In terms of the jump in the number of cases, one of things that we've talked about in the past on this is that with the huge surge in cases in certain countries, particularly in September and October, people got behind on their data.
They ended up with huge piles of paper in terms of cases, etc, and we knew and I actually said to you the last time, we are going to see jumps in cases at certain times that are going to be associated more with new data coming in but it's actually on old cases.
And a couple of days there were about 2,000 additional cases in, if I remember correctly, it was actually the Liberia case report but most of these were old cases because remember they got swamped a couple of months ago with a lot of new cases and just got behind on their data, so a lot of that is about reconciling new data.
If we look at sort of a seven day rolling average number of cases which have been around 1,000, just under that, about 900, there hasn't been a big change in that in the recent weeks.
So the 3,562 cases come largely from the past as well as the present. It's not that the sky has fallen in the past 5 days. Which is good news. But of course, that puts us back to "just" 1,000 or so Ebola virus disease cases a week. In other words, in just 1 week there are more cases than in any individual outbreak since 1976. 

The cumulative EVD case curve at 29-Oct
However, this week has seen a few articles and comments noting that the number of new cases in parts of Liberia seem to have fallen slightly. 

This seems to be a real trend in that there are fewer burials and more empty treatment beds and fewer cases found when sought in the community. Why there are fewer is not precisely known and it is far to early to rely on this yet. But we do know that there are better numbers of safe burials, better education, more experience with the disease, more help and facilities and more PPE comapred to when this started. 

The three countries with intense transmission still require a lot of help from us though - that urgency must not let up. Remember that cases had dropped a lot back in May - and now look where we are.  

If you can't get there in person to offer specialist help, and most of us cannot, keep bringing the issue to the attention of your country's leaders, learn about the virus and the disease from trusted sources and help teach others and head off ignorant comments, and donate some (some more) money to those groups who can make a real difference on your behalf (I've listed some great options here). 

Fighting the fire at its source is still the best way to help save lives in Guinea, Sierra Leone and Liberia and to stop new outbreaks from occurring in other countries.


  1. WHO Ebola Roadmap SitRep#10
  2. Virtual Press Conference transcript

Tuesday, 28 October 2014

Why Ebola virus is not human immunodeficiency virus (HIV)

I'm not an HIV expert and only an Ebola virus hobbyist but let's see if we can list some things that are similar and different about these two viruses.

Some ways that Ebola virus and HIV are similar...
  1. Both are harder to catch than a cold. They do not spread through an airborne route.
  2. Both have lipid envelopes - Ebola virus is about 904-
    1,100nm long x 80nm wide whereas HIV is about 120nm around
  3. Both can be transmitted in blood, breast milk, and through sexual contact, being present in seminal fluid (HIV also in female genital secretions). For HIV the extent of the frequency of exposure and the viral load play during that exposure, play a role in the likelihood of infection; this is not well defined for Ebola virus.[1]
Some ways that Ebola virus and HIV differ...
  1. HIV is an RNA virus that goes through a DNA phase which allows it to hide in our cells while Ebola virus is strictly an RNA virus
  2. Ebola virus infects dendritic cells, monocytes, macrophages, endothelial cells, endocardium, kidney and liver cells but not peripheral lymphocytes while HIV primarily infects CD4+ lymphocytes and also dendritic cells
  3. They differ in the mechanics underpinning the way that they replicate themselves
  4. Ebola virus disease occurs very quickly whereas acquired immunodeficiency syndrome (AIDS) has a long latent period (although there is an earlier more acute disease)
  5. At writing, no antiviral or vaccines exist on the market for Ebola virus or Ebola virus disease; a range of drugs exist to slow or suppress HIV
  6. Ebola virus acutely kills cells, causes coagulation, organ damage and disrupts the immune response without lingering; HIV eventually becomes latent in the cells it infects, integrating with the genome
  7. Ebola virus has 7 genes, HIV has 9 and overlapping reading frames.
  1. Principles of virology. Flint SJ, Enquist LW, Racaniello VR, Skalka AM.3rd Edition. Vol 2. Chap 6.

Saturday, 25 October 2014

Mali makes it 6 countries in the West African Ebola virus disease epidemic

v2 251014

The 6th country in the West African outbreak to host a case of Ebola virus disease (EVD) in 2014, is Mali.

The case was a 2-year old girl who was symptomatic while still in Guinea.

She travelled with her grandmother >1,000km by public transport to Bamako (Capital city of Mali), setting out 19-Oct. WHO are treating the situation as an emergency; there were multiple opportunities for exposure. The case's mother may have died of EVD in Guinea and her grandmother may have travelled from Mali to Guinea to attend the funeral.

The case had contact with health services in Kayes, western Mali, on 20-Oct. She was referred and admitted to a paediatric ward of Fousseyni Daou Hospital 21-Oct with a fever of 39’C, cough, bleeding from nose and blood in her stool). Tests were negative for malaria but positive for typhoid fever. Pain relief was given but there was no improvement. 

Further tests confirmed EBOV 23-Oct at the SEREFO (Center for TB and AIDS Research) laboratory in Mali.

Samples are being sent to a WHO-approved laboratory for confirmation.

The girl has since died.[2]

The 2014 West African epidemic and Central African outbreak of EVD.
Click on image to enlarge. Feel free to use and share this map
(please attribute to this blog).

NB: Nigeria (19-Oct) and Senegal (17-Oct) were declared EVD free.


    Sunday, 12 October 2014

    Ebola double vision....

    A quick post to crudely highlight that total (suspected+probable+laboratory confirmed) Ebola virus disease case numbers have been doubling approximately every month  since June (as far back as I went). 
    Click on image to enlarge.
    The reality is that the most recent reports from the World Health Organization (WHO) may be even less accurate than the underestimated numbers we have become used to during the epidemiological fog-of-war that surrounds any outbreak, epidemic or pandemic. 

    Apart from the most recent update, WHO Situation Reports (SitReps) of late have made a point of highlighting that the numbers have been lower than what those in the field expect is real.
    "It should be emphasized that the reported fall in the number of new cases in Liberia over the past three weeks is unlikely to be genuine. Rather, it reflects a deterioration in the ability of overwhelmed responders to record accurate epidemiological data. It is clear from field reports and first responders that EVD cases are being under-reported from several key locations, and laboratory data that have not yet been integrated into official estimates indicate an increase in the number of new cases in Liberia."

    So, if you are a senior influencer or a decision-maker in your country and if that country, in which you are a citizen, has offered only limited, financial, or non-existent support to this unprecedented outbreak of infectious disease, I suggest the following: Stop disproportionately worrying about the few sporadic but simply controlled EVD cases that your already-straining healthcare budget has to look forward to. Stop worrying about how those budgets will cope with the unnecessary burden of your feel-good but near-pointless rollout of temperature monitoring resources at entry ports. Stop thinking that by blocking flights out of West Africa you will somehow protect your country and the rest of the world from exported cases.

    Think about this instead: If you are not doing your damnedest to insist that your country has put people and equipment on the ground in Liberia, Sierra Leone or Guinea, then you do a disservice to humanity, and on your shoulders be the burden of the many deaths to come. 

    We individual citizens can't do this. You and our governments can.

    Complain about and hide behind who didn't react fast enough if you must, but do be very, very clear in your own mind that now, right this minute, if you are not acting, calling someone, pleading a humanitarian case, then it is you and those like you who are to blame for some of our global villages burning out of control. 

    I don't care a damn if the currency for today's political action is "security" - you find a way to bring it back to being about humanity. 

    We live in an interconnected world and some of those country's citizens are your constituents.

    The global calls have gone out, the Resolution has been passed, the pleas have been made, the situation is clear to all. And you are failing. 

    Get up and do something. Now.

    1. Ebola Virus Disease in West Africa — The First 9 Months of the Epidemic and Forward Projections.
      New England Journal of Medicine. 23-Sept. WHO Ebola Response Team

    Tuesday, 7 October 2014

    Ebola index: Virology Down Under posts...

    To make it a little easier for me to keep up, I thought an index of  my key posts - some of which address your most pressing concerns about Ebola virus, ebolaviruses and Ebola virus disease (EVD) - would be useful.

    1. The tallies and graphs from the major countries that have hosted Ebola virus disease cases in West Africa. Updated as soon after the World Health Organization (WHO) releases their figures as I can manage.
      Ebola Virus Disease (EVD) 2014 West African outbreak..
    2. The partner post to #1 but in maps and historical numbers.
      Ebolavirus disease (EVD) cases, clusters and outbreaks mapped out...
    3. A summary of what we know about how the Ebola virus is transmitted between humans.
      Ebola virus may be spread by droplets, but not by an airborne route: what that means
    4. The companion piece to #3 - highlights that we can force Ebola virus into an aerosols in non-human primates (not hiding this), and that pigs also seem to produce aerosols...but that this is not the same as natural human virus acquisition/disease which is due to direct contact between body fluids and mucous membranes/broken skin (includes physical touch and propelled).
      Ebola, pigs, primates and people
    5. Why this epidemic is extremely unlikely to produce a variant of Ebola virus that changes so much (accompanied by changes in the host), that it becomes an "airborne virus".
      The wind beneath my Ebola virus....
    6. Some scientific literature to underscore the risks of acquiring Ebola virus from a very ill person's blood, sweat, spit and tears.
      Ebola: Blood, sweat and tears...
    7. Some scientific literature and discussion to highlight the chronic risk of acquiring Ebola virus infection from the semen of a convalescent male.
      Ebola virus in semen is the real deal....
    8. A post about the many things that lead to healthcare worker (HCW) Ebola virus infections. This was in response to a CIDRAP article and to the increasing narrative that because of a high toll among HCWs, there must be something changed about this virus making it "easier to catch than what we have been told". Which has to date not been backed up laboratory science, epidemiology or the observations of those working in West Africa. 
      Ebola virus, HCWs infections and personal protective equipment..
    9. A new graphic to even more simply explain the differences between an airborne transmission route and a short-distance wet droplet/cough route of transmitting viruses like Ebola virus.
      It's what falls out of the aerosol that matters....
    10. A thought-provoking post about what to call the way in which viruses like Ebola virus may be transmitted since they are not truly airborne but may be coughed or vomited across short distances as big wet droplets. Airborne vs Propelled.
      What words would you use to separate influenza spread from Ebola virus disease spread?
    11. A short brief on the different variant, still from the Zaire ebolavirus species (same species as that ravaging West Africa), concurrently circulating in the Democratic Republic of Congo (DRC).
      The battle of Ebola gains a second front...the Democratic Republic of Congo (DRC; formerly Zaire)
    12. Some of the many fake or non-Ebola virus disease images circulating on the interwebs. Help enlarge this or solve the unknowns, if you can.
      Fake/wrong Ebola virus disease images...
    13. How to use the perfect terms to discuss Ebola virus. How does Ebola virus differ from EBOV, differ from ebolaviruses, differ from Ebola virus disease? A primer on the lingo and how it compares to cars.
      Behind the naming of ebolaviruses...
    14. How can you help? Donate money and help provide protective equipment for the heroic efforts of those willing to face down Ebola locally in West Africa or after driving/flying in.
      Protect the healthcare giver>>save lives>>stop Ebola virus disease
    15. Application of Prof David Fisman's predictive Ebola modelling.
      Updating a model of a modern Ebola epidemic...
    16. A term to better explain the crude ratio of people who have died in the midst of a chaotic epidemic.
      The proportion of fatal cases (PFC)...
    17. Some hints and tips on how to get the most from commonly used graphs on Virology Down Under.
      How to read a VDU graph...
    18. How to read my graph depicting Ebola virus case numbers between reports.
      Case number changes between Ebola virus disease reports...
    19. An idea that could be used by Australia to more safely allow it to provide/encourage/permit the sending of human help, not just money, to West Africa.
      Australia's response to Ebola virus disease in West Africa: is too little enough?
    20. A ranty reminder the outbreaks, epidemics and pandemics are chaotic things driven by chaotic humans. Numbers of cases never account for every case..because chaotic. Don't expect them too.
      The numbers are underestimates...
    21. A theory about the cumulative case and death graphs that suggests a possibly useful predictor of things beginning to run out of control.
      The control gap...

    Saturday, 4 October 2014

    What words would you use to separate influenza spread from Ebola virus disease spread?

    I need your help.

    I have spent umpteen hours on trying to make this message simple. None of that has been aided by the way that the CDC, the WHO and now the UN use the terms and words confusingly to convey messages to the public. The message is often delivered as if they were sitting around their meeting rooms talking to other health and science professionals. In my opinion, we all look to these guys for simple clear and consistent messages. Right now they need to do much better to convey complex concepts, simply, quickly and more often. Education helps prevent panic, mistakes and conspiracy theories (well-as much as anything can anyway).

    So here is another attempt by me to get this wording into line with what the rest of world can make sense of. 

    I could also really use your input to make this work - so leave a comment below, or Tweet me @MackayIM or email me or send me a carrier pigeon - with how to make this message simpler for you and your kids and your grandparents and that weird uncle you stay clear of at Christmas, to understand. 

    Let's crowdsource a solution to this confusion, help out others and then see if the major public health bodies can come on board.

    Propelled droplets versus a cloud of suspended.
    This post and issue have been fuelled most recently by the Ebola virus disease (EVD) epidemic but is also fuelled by my experiences in talking to people about the MERS-CoV and influenza A(H7N9) virus outbreaks. They are respiratory viruses while ebolaviruses are not. Different viruses yes, but common concerns for people and to the issues around trying to understand overly technical terms when they are used differently in everyday life. 

    Public health speaking is very public.

    Public health issues are spoken about on a global stage, more now than ever. It is up to us to better define the right words and use them consistently. That has definitely not happened for "aerosol" and "airborne". 

    We professionals can't just sit back and expect our stakeholders to come along with us for the ride - they will get confused when imagery conflicts with lingo and official statements, and when different public organizations disagree with each other or use tiny but significant differences in their language to communicate risks. 

    People are not stupid and deserve more respect than they are currently getting from those who should know much, much better about how to work alongside the public (public health and all).  

    So what is the problem here? 

    Droplets would probably be an ideal word to differentiate from airborne - and it has been used to differentiate the level of precautions of personal protective equipment (PPE) to prevent infections - droplet precautions and airborne precautions - but the evil physicist types have ruined the use of that word for us by introducing droplet nuclei (the part of the aerosol that lingers in the air and can convey those viruses that survive in it, to a new person to infect them). Physicists like technicalities.

    So the problem is trying to define a name for that other process that can simply and clearly describe infectious disease transmission of viruses & bacteria that are propelled from/by the sick person, across the gap between them and an uninfected person, measurably infecting the recipient. The name should make clear that it is a different process to the one that sees a person get sick by inhaling infectious viruses or bacteria held aloft by the air, in a cloud, made by a previously ill person, that has been hanging around for perhaps an hour or more. That one is an airborne route of transmission. 

    Some people have berated me for talking technicalities and semantics in recent days while I try to better define this. Tough! Water off an influenza-host's back. Words have meaning and impact and useful words are needed. Especially when everyone is freaking out over a disease they have only read about in dramatized books or seen in Hollywood blockbusters. The two processes listed above are distinct and different for some viruses & bacteria. But it is biology and nothing is 100%, except death. 

    Some infections, like those leading to influenza, could result from both processes. Some, like Ebola virus disease have never been observed in humans via one route (airborne), whereas there is a defined risk of them occurring by the other (direct contact between a range of virus-laden body fluids propelled onto a mucous membrane). Yes, coughing a tiny barely visible droplet onto someone else's mouth is direct contact between the wet fluids and the mucous membrane.

    They two processes are battled differently. We protect ourselves from them differently. And names can tell us about the different levels of risk. But what is that other route to be called? 

    I have an idea. First some perspective.

    Ways to think of the differences.

    A word cloud of ways to think of the
    two different processes of spreading viruses
    or bacteria that result in infection and disease
    in humans.

    v2 Thanks to Nina West for good analogy (Fog/Rain)

    The idea.

    How about we call the process of relatively short (up to about 3m) distance, coughed/sneezed/vomited wet droplet transfer of disease-causing doses of viruses or bacteria, "Propelled"?

    Over to you, world.

    Some greats from the comments below...
    • "void the spray and live another day"
    • Only touched by air, no need to care. Where it splatters, that's where it matters

    Friday, 3 October 2014

    Evaluating a traveller being considered for Ebola virus disease

    A lot of other content from the United States Centers for Disease Control and Prevention can be found at:

    The richer end of the world finds creative ways to spread Ebola virus... [UPDATED x2]


    Amendment: It has been quite correctly noted below, by the moderator in a personal communication (or 4) and by others, that this image was posted or taken from a Dallas/Fort Worth TV (WFAA) station's chopper on 2-Oct. The infected man vomited 28-Sept, as he headed to hospital. 
    So let's say about 72-hours had passed while the vomit sat outside on a non-ceramic/steel surface (these are used in controlled lab experiments to show virus stability-perfect world stuff) through multiple cycles of Texan day/night, high/low temperatures. Okay. The power-washing process is thus extremely unlikely to have generated infectious droplets. Risky and ridiculously long period to leave potentially Ebola-laden vomit out in the open of course, but extremely unlikely to be a source of infection during the power-spraying (water-blasting/gurneying). Apologies for adding to the fear-mongering.  -IanM

    This from a Tweet sent to me by @LonnieRhea thanks) 

    So far the Dallas Ebola virus disease case has been a great learning experience for the United States. 

    It really does serve to highlight that humans are what make virus outbreaks...become outbreaks. 

    Viruses are nothing without us. And we are so eager to oblige in spreading them around.

    Hopefully the virus in that vomit had been inactivated by heat, or the nature of the surface it was on or by drying out before being stirred up by a high pressure water blaster. And hopefully they sterilized their shoes and clothes and...sigh.