Sunday 23 August 2015

Whether MERS-CoV spreads or stops is entirely up to the hospitals...

The very steep rises in Middle East respiratory syndrome coronavirus (MERS-CoV) cases seen in the graph below are not due to overwhelming and constant exposures to infected camels resulting in human cases of MERS. 

Those upwards inclines are mostly because humans are just numbskulls.

MERS-CoV cases worldwide up to 22-AUG-2015.
Click on image to enlarge.

We propagate epidemics. We create our own headaches in this arena. Many viruses wouldn't break out if we didn't create the circumstances for an outbreak. The biggest headache? Infected patients who spread virus to uninfected patients and health workers when they are in unprotected close contact in a healthcare setting.

We can go on and on bemoaning the many knowledge gaps in our understanding of MERS-CoV - we did and listed some recently - but that's really an academic endeavour in the short term. Three years later (not really short term) we are still seeing the basic problem of hospitals becoming hubs for MERS-CoV transmission, MERS disease and the death of some of those most vulnerable to MERS-CoV infection. Hospitals. Places filled with already sick people. Sick people who can be made much, much more sick by a MERS-CoV infection. 

In the case of MERS cases - as we have seen time and time and time again in the short space of time since 2012 - one or a few cases get into a hospital environment and catch the hospital completely unprepared for such a...poorly transmitting respiratory virus infection. 

It really doesn't matter if the earliest cases acquired virus from a camel or a community case or a family member - the containment of that infection is what matters to prevent a subsequent outbreak. 

And so they fail to contain it. Maybe the way we receive patients should be looked at afresh from an engineering perspective? Mainly though, this is a people problem. Those people receiving, managing and working in the hospital create the circumstances by which this opportunistic virus can spread well beyond what its capability suggests it should.
Heavier wet droplets versus 
near-weightless droplet nuclei.
Impact versus cloud.
Click on image to enlarge.

To stop transmission in hospitals, basic protocols of personal hygiene and personal protective equipment seem to work.

So, from a complete non-expert, here are my simplistic thoughts: 

  1. Wash off an infected patient's virus (which includes constant cleaning of surfaces around the patient and constant mindfulness about one's personal hygiene extending to those not caring for a patient-e.g. cleaning, ward, transport and administration staff
  2. Protect upper airway (mouth, nose and eyes) mucous membranes from being exposed to infectious droplets propelled from an infected patientIf that isn't working (but past fixes suggest it has) there are stepped up precautions to try to prevent airborne transmission by floaty clouds of infectious virus (if it can remain infectious in such clouds).
Once that protection is a standard procedure in the hospital, perhaps others could pick up their feet on trying to sort out the specifics of how the virus manages to transmit and which mucous membranes are the ones we need to cover up. 

Let's not forget this is all just as relevant to infections by much better studied pathogens including measles virus, respiratory syncytial virus, human metapneumovirus, adenoviruses, influenza viruses, other coronaviruses and rhinoviruses. They can all be spread in healthcare settings - and more efficiently than MERS-CoV it seems. They can also have a big impact on vulnerable patients.

But baby steps.

Saturday 22 August 2015

Watch that last step, it's a doozy..

For each of the past five weeks, Guinea has continued to throw up 1-5 Ebola virus disease (EVD) cases. But transmission chains are known and so this will hopefully stop very soon. Tracking down contacts that have been lost to follow-up and unknown spread in the community remain big variables in this equation. 

Sierra Leone has reported 1-3 EVD cases over that period - but importantly, the last of those cases was reported by the World Health Organization (WHO) on the 10th of August - 12 days ago. We've seen one full case-free reporting week so far, and the next is looking good for Sierra Leone as well. 

The latest confirmed EVD case data plotted below - which stretches from February to last Friday - we can really see how the death of an epidemic has occurred in steps. For Liberia, there was a very dramatic and precipitous decline, but for Sierra Leone and Guinea, it has been a slower process. 

It looks like we will see an end to the EVD epidemic as we saw it begin, with Guinea harbouring cases. 

And then we wait, watch and remain wary as the 21-day individual incubation periods elapse, then the 42-day national incubation periods lapse, indicating no known ongoing transmission, and finally the many months of vigilance pass. I'm not sure we're really that confident about the upper limit of this final step yet. 

I can't imagine the period of vigilance will pass entirely without incident - Liberia has already taught us a hard lesson about occult transmission - but we've all been wrong about Ebola virus before and it would be great to be wrong about this. Here's hoping those final steps are a smooth descent to zero.

Confirmed cases added by each WHO Situation Summary of Situation Report.
Modified from my Ebola virus disease graphs and tallies page.
Click on image to enlarge

Sunday 16 August 2015

Snapdate: Ebola virus diseaseClick on image to enlarge.

This is one of the data visualizations from my Ebola virus disease (EVD) graphs and tallies page.[1]

A crude extrapolation from current publicly available Ebola virus disease (EVD) confirmed case numbers. To see how I made this please visit here.[2]
The P-value for this linear trend model is <0.0001. 
The standard error = 6.13; R-squared = 0.20.
Click on graph to enlarge.
The first time I posted it I wondered if the end was in sight. That was 6th of May. Over three months later I'm wondering that again - but this time things are a bit different. There has been a steady decline in new cases, also in cases that cannot be tracked back to a known source and in cases found only after they have died of EVD. There have also been the first very promising results from one of the vaccine candidates in Guinea [4] - which has always been a difficult locale for the control of EVD case activity.

So it does look much more likely that the end to EVD in West Africa, or at least an end, is nigh.

By "an end" I mean that we may be close to seeing the cessation of new cases popping up in transmission chains each and every week. We may soon be seeing zero new cases for long periods of time. Those blissful stretches however, may be punctuated by a case arising from parts unknown. They may be tracked to a sexual transmission event, or their origin may never be fully understood. We saw this scenario in Liberia.[3] Virus characterisation indicated that the Ebola virus variant from the young Liberian man was most closely resembled other viruses that had been circulating in Liberia weeks before; the exact source of his infection though, remains unknown.

So we're not at all free and clear of this virus yet - but we are getting very close to shifting into another phase. It's still a long haul with many weeks of anxious waiting and heightened vigilance as well as the need to retain the capacity to cope with a new case or cases. But that said, we do seem to have taken one more step back from the precipice we once stared into as we imagined an Africa fending off a rolling EVD epidemic - and a world at risk as well - however unlikely that should have been. 

Tuesday 11 August 2015

Queensland influenza age shift still shifted...

Figure from State of Queensland (Queensland Health) report found here includes data up to 9th August 2015.
Images excised from PDF and pasted together using Adobe
Photoshop CC 2015.0.0
Click on image to enlarge
Also interesting:

  • 3.3X more influenza type B viruses than influenza type A viruses in week to 9th August
  • a proportion of the influenza viruses were further genotyped
  • 44% of that proportion were influenza B viruses of the Victoria lineage which is not the lineage in the trivalent vaccine this year (it is in the quadrivalent vaccine though - see full report for detail) 
    • NOTE - the report is not clear on how many genotyped specimens this represents
  • As you can see in the figure below - the 'flu season is still very much underway in Brisbane
  • Brisbane is also experiencing its own little 'mass gathering' which started last Friday - the Brisbane Exhibition.
Appendix 1 from the State of
Queensland (Queensland Health) report found 
here, including data
up to 9th August 2015.
Click on image to enlarge

Saturday 8 August 2015

Queensland influenza sees a shift in age...

Image adapted from Geoscience Australia,
The Australian Government.[3]

The media Down Under have been doing their thing this influenza season...

...lots of inflammatory (pun intended) headlines to make us all fear just about everything and everyone. Blah.

Nonetheless, it is flu season down here - and hopefully you gave vaccination a try this year, or you got your annual shot. Top marks if so! If you can safely and pretty painlessly dodge a preventable disease, save yourself some misery, avoid making your kids sick - who will require time off to be looked after, not make Aunty Robyn crook as a dog and not put Grandad's ailing ticker under extra stress...why wouldn't you? 

VDU Figure 1. Figure 2 from the State of
Queensland (Queensland Health) report
found here.[1]
Click on image to enlarge
Thanks to the excellent and publicly available wealth of data presented by the epidemiologists of the State of Queensland (Queensland Health), I talked about influenza in Queensland and the distribution of types (i.e. Flu A or B) and subtypes (e.g. H3N2 or H1N1) last year.[2]

In 2014, influenza A viruses were the big bad, but in 2015, as we can see in VDU Figure 1 (orange), influenza B viruses are ruling the mean streets.

VDU Figure 2. Appendix 1 from the State of
Queensland (Queensland Health) report
found here.[1]
Click on image to enlarge
From the look of VDU Figure 2, the influenza season remains in full swing (hint-get that vaccination if you haven't already). 

VDU Figure 2 also shows that things are not tracking all that unusually for a Queensland influenza season when you compare this year to curves from the past 5 years. So I'd suggest taking those media headlines with a box of tissues!

However, something stood out to me when looking at the latest report so I went back and cut-and-pasted the age and sex graphs from the past few consecutive weeks to make VDU Figure 3. Sure enough, there was a particular spike in the 5-9 and 10-19 year old age bands (yellow arrows in graph boxed in red). Even allowing for changed y-axis scale in the first 4 graphs (dates are listed in each graph's legend) these 2 bands seem to have risen just in the past reporting week. 

Still, the overall pattern of rising case numbers, a dip in the 20-29 year old age band, then a rise before a consistent drop off is retained. Is this the result of school kids returning from school holidays on the 23rd of July, sharing their viruses, incubating an infection and becoming ill? If so - will we see a rise in parent - age age bands in the report after next's? Let's watch and see!

VDU Figure 3. Figure 4s from previous weeks of State of Queensland (Queensland Health) report found here.[4]
Images excised from PDFs and pasted together using 

Adobe Photoshop CC 2015.0.0
Click on image to enlarge

post-Ebola syndrome or just chronic Ebola virus disease...?

The number (y-axis) of confirmed EVD cases added
by each World Health Organization report
over time (x-axis) as of 06AUG2015.
See here for more graphs and tallies.
Click on image to enlarge
There are at least 13,000 people in Guinea, Liberia and Sierra Leone who have survived an encounter with the Makona variant of Zaire ebolavirus (EBOV) since December 2013.1

But that’s not where the story, or the suffering, ends for these people.

Following the resolution of acute Ebola virus disease (EVD), there is the spectre of a lengthy period of subsequent symptoms, sometimes called ‘post-Ebola syndrome’ (I’d prefer post-Ebola virus disease syndrome or PEVDS), which is similar to that found among survivors from past outbreaks.2,3

In Uganda in 2007, EVD survivors were more likely than controls to suffer from retro-orbital pain, blurred vision, hearing loss, neurological abnormalities, sleep disturbance, arthralgias (joint pain), memory loss, confusion, difficulty swallowing and chronic health problems.4,5 These sequelae can reportedly persist for more than two years.4

In West Africa up to 50% of EVD survivors report these and other symptoms as well as fatigue, pressure in the eyes, uveitis (eye inflammation), blindness, hair loss, myalgias, swelling, menstrual irregularities, rashes and shooting pains.6-11 Eye problems have been reported in around a quarter of survivors.11 Anorexia was reported by 98% of survivors in a study of 105 participants with joint pain (87%) and back pain (46%) also common.12 This study also reported difficulty in short-term memory (27%), headaches (22%), sleep difficulties (19%), insomnia (13%), dizziness (11%), abdominal pain (32%), constipation (14%), decreased exercise tolerance (77%), decreased libido (23%), and sexual dysfunction (20%).12 There are also issues of stigmatisation, psychosomatic illness and a broader psychological impact among survivors, including depression and post-traumatic stress.9,12

In at least a few of these instances of PEVDS, viral genome or infectious virus has been detected, sometimes at the site of disease – the eye for example.13 Because of this persistence of infectious virus at the peripheries and because of chronic pain, ongoing symptoms of acute disease and also the progression of disease as new symptoms – it may be prudent to stop calling this a ‘post-EVD’ syndrome and recognise this as part of EVD – redefining EVD into an acute phase and a chronic phase.

Much more work is needed to understand what causes the symptoms of chronic and evolving EVD. Some knowledge about the pathogenesis and transmission risks of EBOV is still lacking along with the lack of capacity in Guinea, Liberia or Sierra Leone to culture infectious virus. Physical containment (PC) or biosafety level (BSL) 4 laboratories are not available in West Africa, but are needed to work with known, high concentration samples and pure cultures of EBOV. That requirement appears a little excessive given the large number of humans who have hosted, cared for, tested or otherwise handled massive EBOV loads over the past 20 months – but responding to a crisis and planning to do research (also a much slower process) are two very different beasts.

Keep in mind that one privileged site, the testes, has not been a cause – as far as we know and have actively looked for – of more than a tiny number of EVD cases.14 We can of course academically argue that any case is one case too many and that one case is all that started this epidemic - but it would be helpful to have a better idea of the true infection risk posed by EBOV in these immune privileged sites, based on the published results of more testing.

In the case of EBOV in the eye (see here), tear fluids were not found to contain viral RNA, so infectious virus does not seem to be a significant risk to other people if contained within an intact infected eyeball – apart from causing ocular disease - but that is based on a single case study.

Apart from testes and the eye (perhaps the foetus/placenta), are any other fluids or tissues harbouring infectious EBOV for extended periods? Could synovial fluid be to joint pain what aqueous humour is to eye problems (h/t @gwendolbowling)? Can we assume persistent viral RNA detection equates to replicating infectious virus (yes, in my opinion)? What is the frequency of persistent infection among the 13,000 survivors? Exactly what anatomical and host factors are involved in persistent infection? Just how long does virus replicate after the acute signs and symptoms of disease have cleared?

Other viruses, for example Dengue virus and Chikungunya virus are known to cause chronic joint issues so this is not totally new ground, but the pathogenesis of that disease is also not nailed down. So, how will new chronic EVD knowledge be useful for other virus infections, including those that we may have not yet have considered to play similar roles at immune privileged sites or may not be typically associated with post-acute disease signs and symptoms?

In June, 2015, the National Institutes of Health in the United States launched the Partnership for Research on Ebola Virus in Liberia (PREVAIL) III study in partnership with Liberia’s Ministry of Health aiming to understand the long-term health implications of EVD.15-17 There is a similar study in Guinea.18

As you’d expect, there are not yet any specific licensed antiviral treatments in routine use for persistent Ebola virus infection, just as there are none for acute EVD. But supportive treatment – treating the symptoms of disease rather than the underlying viral (or whatever) cause – is ongoing. Anti-inflammatory eye drops are used…but with caution.11

The EBOV epidemic keeps teaching us new things; a very costly education.  


1.  Ebola survivor meeting explores research priorities, 'biobanking'. Center for Infectious Disease Research and Policy, 2015. (Accessed 8/8/2015, at
2.  Kibadi K, Mupapa K, Kuvula K, et al. Late ophthalmologic manifestations in survivors of the 1995 Ebola virus epidemic in Kikwit, Democratic Republic of the Congo. J Infect Dis 1999;179 Suppl 1:S13-4.
3.  Rowe AK, Bertolli J, Khan AS, et al. Clinical, virologic, and immunologic follow-up of convalescent Ebola hemorrhagic fever patients and their household contacts, Kikwit, Democratic Republic of the Congo. Commission de Lutte contre les Epidemies a Kikwit. JInfectDis 1999;179 Suppl 1:S28-S35.
4.  Clark DV, Kibuuka H, Millard M, et al. Long-term sequelae after Ebola virus disease in Bundibugyo, Uganda: a retrospective cohort study. Lancet Infect Dis 2015.
5.  Bausch DG. Sequelae after Ebola virus disease: even when it's over it's not over. Lancet Infect Dis 2015.
6.  Free from Ebola, survivors complain of new syndrome. Reuters,, 2015. (Accessed 25/5/2015, at
8.  Ebola: Surviving Survival - Life after recovery. 2015. (Accessed 25/5/2015, at
9.  Life After Ebola: Pain, Flashbacks, and 'Post-Ebola Syndrome'. Vice News. (Accessed 25/5/2015, at
10.  Sierra Leone: Helping the Ebola survivors turn the page. 2014. (Accessed 25/5/2015, at
11.  Ebola Survivors Face Lingering Pain, Fatigue and Depression. New York Times, 2015. (Accessed 8/8/2015, at
12.  Qureshi AI, Chughtai M, Loua TO, et al. Study of Ebola Virus Disease Survivors in Guinea. Clin Infect Dis 2015.
13.  Varkey JB, Shantha JG, Crozier I, et al. Persistence of Ebola Virus in Ocular Fluid during Convalescence. N Engl J Med 2015.
14.  Christie A, Davies-Wayne GJ, Cordier-Lasalle T, et al. Possible sexual transmission of ebola virus - liberia, 2015. MMWR Morb Mortal Wkly Rep 2015;64:479-81.
15.  Blood, Sweat and Tears: Study Will Watch Ebola Survivors. NBC News, 2015. (Accessed 23/6/2015, at
16.  Study of Ebola survivors opens in Liberia. 2015. (Accessed 8/8/2015, at
17.  Ebola Virus Disease Survivors: Clinical and Immunologic Follow-up., 2015. (Accessed 8/8/2015, at
18.  Results of the meeting on survivors of Ebola virus disease. World Health Organization, 2015. (Accessed 8/8/2015, at