VDU's blog: EBOV

Showing posts with label EBOV. Show all posts

Saturday, 13 May 2017

Ebola returns to the Democratic Republic of the Congo (DRC): Zaire...

UPDATE No.1 14MAY2017 AEST

UPDATE No.2 15MAY2017 AEST

UPDATE No.3 17MAY2017 AEST

UPDATE No.4 18MAY2017 AEST

UPDATE No.5 18MAY2017 AEST

UPDATE No.6 10MAY2018 AEST

The World Heath Organization alerted the world on May 12th [1] to an outbreak of Ebola virus disease (EVD) in Likati, a remote region in the Bas-Uele province of the Democratic Republic of the Congo (DRC).[4] The news had been communicated to them on the 11th May by the DRC Ministry of Heath.[6]

This is the 8th recorded outbreak in the DRC and it is hoped that their expertise, together with a range of rapidly mobilised outside expertise, will contain this one quickly and with a minimal loss of life.[5]

It reportedly took 10 days for the first samples to reach the lab in Kinshasa for testing.[8] Google estimates about 47 hours to travel the ~3,000km from Kinshasa to Aketi (about 50km beyond Likati via Google's inland suggested route - doesn't account for off the 'main' road and forest parts) - it doesn't give estimates for Likati direct. The WHO explained...

See thread here if you use Twitter.

The journey to Likati is not an easy one.[16] Planes and helicopters are being used and there are questions around how secure the area is.[18] While remoteness is anecdotally beneficial for containing the spread of an outbreak, there are 2 clusters of illness and death outside of Bas-Uele, marked on the Ebola SitRep maps, which may test this theory.[17]

There are reportedly 300,000 (GAVI/Merck emergency stockpile [13])-700,000 doses of the rVSV-ZEBOV vaccine which has been reported to be highly effective at preventing EVD.[3,9,10]

Early numbers were a bit confusing [2] - as often happens in the fog of announcement of an outbreak - but since 22nd April there seem to have been:

20 suspected and confirmed cases in total [17]

3 fatal cases (proportion of fatal cases: 15%)

1 of 5 samples was initially laboratory confirmed (PCR) at Institut National de Recherche Biomédicale (INRB) in Kinshasa - it tested positive for Zaire ebolavirus
a 2nd case has since been Zaire ebolavirus lab confirmed [12]; 3 have tested negative [17]

at least 6 cases hospitalised [7]
≧416 contacts being traced [17]
1st case - 45 year old (or 39yo) male (45M) transported by taxi; died on arrival [11]

driver fell ill and died
carer of 45M fell ill and died (=25 contacts)

Nambwa health district has notified the greatest number of the earliest cases: 13 in all, with 2 deaths (case fatality: 15%).[15]

References...

Maps used to help place Likati and Bas-Uele...

Updates...

Fixed spelling mistakes in Likati, added detail about sampling delays

Added references 10-12; noted 2 cases now confirmed, 19 suspect cases in total
Update on where the 300,000 vaccines come from [13]
Update on contacts and ReliefWeb and WHO references
New SitRep from WHOAfro - altered case & testing numbers
Replaced maps to add in the correct population!

Monday, 12 October 2015

Jon Snow is remarkably well informed compared to us...

...because we clearly know almost nothing when it comes to the specifics of where Ebola virus (EBOV) can, in some portion of survivors, hide.

What triggers EBOV to come out of hiding? If indeed that is what it has done within PC, the United Kingdom nurse who seems to have recently become ill while (or due to) hosting a reappearance of EBOV in her blood - 9 months after her blood was defined as containing no detectable EBOV.

This is not a new infection - but a return of a virus that had not been cleared from its hidey hole(s).

There are obvious concerns to be discussed around this, including:

What triggered its re-emergence
Is this a strange and rare event or a more common one?
Was the virus hiding in PC's central nervous system (she has meningitis-like symptoms reportedly) or in another place or places?
Is the thyroid a site of persistence?
Did the mysterious antiviral treatment she was given alongside a plasma treatment in 2014/15 act to push the virus into hiding?
Has the activated virus mutated in any significant way during its holiday out of the bloodstream?
Can EBOV become truly latent or at least dormant (still producing proteins, but not infectious virus particles) when off the beaten track, or is it constantly replicating?
Is PC suffering from full-blown Ebola virus disease (EVD) now, or a disease due to tissue or organ damage from her earlier infection - although if she has detectable EBOV in her blood, one would assume it is EVD.
What the hell are a "lucky set of genes" in the context of a return to systemic EBOV infection?

Below are some known and some proposed/possible/unproven sites at which EBOV may linger, avoiding or not exposed to clearance by the full force of our immune response.

In the future, perhaps tomorrow, in a non-rich nation, will others become infected from a convalescent patient who experience a return of EBOV long after they were declared virus-free based on a their blood test results. Has that happened already? Will they be our colleagues, friends or family members? The sooner we hear more about what is going on with PC, the better prepared those on the ground will be to intervene. Also, those tending to convalescent health workers in countries around the globe.

Communication has always been a key issue for EVD and other emerging diseases. Have we been listening?

We know nothing but we can learn. Will we?

Friday, 3 July 2015

Ebola virus: wild and domestic animals, plants and insects...

This post has been moved to the new Virology Down Under platform on Wordpress.

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Apologies for any inconvenience.

-Ian

Saturday, 21 February 2015

Ebola virus disease: obliterating a variant and stalled case decline...

We've seen the words vigilant and vigilance used widely in recent weeks, ever since we entered a "new phase" of the Ebola virus disease (EVD) battle/fight/war.

The reason for vigilance in all things to do with this campaign has become obvious as the weeks have passed; the reduction in cases has stalled.

I've very crudely drawn in some trends below. Whether you agree with them or not, it is clear that since the fast fall in confirmed cases reported between November-January, it seems to have become very difficult to stamp out the last fires of EVD.

The phases.
(Very) rough trends in the number of EVD cases over time.
Date from World Health Organization situation reports (SitReps)
and situation summaries (SitSumms).
Click on image to enlarge.

Liberia has come the closest to completing this goal of obliterating the Makona variant of the Zaire ebolavirus (EBOV|Makona) with just 3-9 confirmed cases between World Health Organization (WHO) Situation Report (SitReps) during any of the past 7 weeks. It seems that recent cases can be traced to known transmission chains too and that means no surprise outbreaks.

However, the people of Guinea and Sierra Leone have not quite got the messages that those in Liberia seem to have embraced (without touching!) so admirably.

In the last WHO SitRep [1] it was noted that 39-45 unsafe burials (probably not all that occurred) occurred in a week and >40 EVD cases were identified post-mortem. This last observation means exposure of the community to the virus, not getting help and treatment for ill people, and unnecessarily requiring contact tracers to play catch-up. Bad for the infected people their friends and families and the response to EVD. It doesn't have to be that way.

This paints a picture of problems with Ebola outreach and education, communication and cooperation. Those things will keep the latest EVD "phase" chugging along.

We do need to destroy this variant of Ebola virus by isolating it in the last human cases in each of Guinea, Liberia and Sierra Leone. Once those people recover or regrettably die, EBOV|Makona will be gone, except for what's in lab freezers around the world and in sequence databases thanks to the efforts of a few expert research teams. Once gone from "the wild", the evolutionary clock resets back to the EBOV variants in the animals of the forest.

EBOV|Makona knows too much; it has seen too much; it has learned too much, to be allowed to "live". It has been passed through humans too many times and while there is a vanishingly small chance it will sprout wings, it is still a virus that spreads relatively easily under the right conditions and circumstances. Explosive loss of 8 litres of fluids a day provides many ways to pass along this blood/gastro virus. EBOV|Makona may also have adapted, and continues to adapt, in other ways that would mean its stay among humans becomes lengthy and its dissemination more widespread.

More bad news from an unsuccessful obliteration of EBOV|Makona-smouldering EVD in Sierra Leone and Guinea may release new case embers that drift across borders and set new fires in other countries. We don't need hundreds of cases a day for that to happen.[3] We know cases also fly with the aid of planes (not wings). And the cycle could renew. I don't think we'll see such big outbreaks of EBOV|Makona again, for reasons I laid out here, but chasing new fires is more work than stamping out the remnants of old ones. Vigilance and action.

I think vaccines still have an important role to play in the final phase of this epidemic, even if only 3 new healthcare worker cases were noted in the past SitRep week. Vaccine given to more than just healthcare workers could be useful here if others will accept the needle.

Ebola outreach
Education
Communication
Cooperation

Oh, and vigilance.

References...

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.

References..

Thursday, 21 August 2014

Ebola virus in semen is the real deal.... [UPDATED]

The World Health Organization (WHO) Ebola virus disease factsheet notes that ebolaviruses may be transmitted via the semen of a male who is getting over an ebolavirus infection, for a period of 7-weeks (~49-days).[1]

The European fact sheet for health professionals and a Public Health Agency of Canada Pathogen Safety Data Sheet both note the 7-week figure, the latter also adds a 61-day figure.[2,3]

The United States Army Medical Research Institute of Infectious Diseases (USAMRIID) Medical Managements of Biological Casualties Handbook (7th edition) notes a 3-month (~80-days) period, during which one should probably avoid sexual relations so as not to deliver virus directly to a mucosal surface.[4]

Semen is therefore listed as one of the body fluids from which Ebola virus disease may be contracted.

While convalescent patients seem to be discharged before 7-weeks have elapsed, I presume the men are made very aware of this risk. This was specifically noted in one of the studies below. [8]

But I find it hard to just accept things.

As a scientist I'm used to looking for the little bracketed or superscripted numbers or perhaps "(Scientist et al)", at the end of sentences. Then I can check out the information source for myself. So here, I thought I'd try and add those and pt it altogether in one place here - and you can do your own checking out if you feel the need.

Here are the research papers I've found for EBOV so far (there are also Marburg virus studies) - by all means send me any others I've missed and I'll add them.

Bausch and colleagues [5] were able to isolate, in cell culture in the laboratory, infectious Ebola virus (EBOV) from the semen of 1 of 2 samples from a single recovering patient who had EVD.

The sample was collected 40-days after disease onset; at 45-days he was no longer positive for EBOV
No acute phase (active infections) samples were tested.
1 of 2 samples were also positive for EBOV RNA by RT-PCR (detecting a portion of the virus's RNA genome)

Rodriguez and colleagues [6] could isolate infectious EBOV from seminal fluid 82 days after disease onset from a 27-year old male (also RT-PCR positive then). A sample at 51-days after onset was RT-PCR positive, but did not yield infectious virus.

EBOV RNA , but not virus, in 3 other convalescent cases (33, 29 and 25-years of age) at times ranging from 57 to 101-days after disease onset.

Rowe and colleagues [7], who examined the same patients, detected EBOV RNA by RT-PCR from 4 convalescent cases (27, 25, 29 and 33-years of age as above) at times ranging from 47 to 91-days after disease onset

No infectious virus could be isolated and no viral antigens were found

Emond and colleagues [8] were able to isolate infectious EBOV from seminal fluid collected 39 and 61 days after disease onset

No EBOV was isolated 76, 92 or 110-days later

So if you are a man who has been diagnosed with an Ebola virus infection and survived, please, seriously, take extra care to practice safe sex. Use a condom. Or, even safer, just wait.

References...

Sunday, 17 August 2014

Ebola, pigs, primates and people

This is a companion piece to my collaborative article, Ebola virus may be spread by droplets, but not by an airborne route: what that means, posted a couple of days ago. I suggest you read the both together.

In this post, I'd like to make sure we all understand that an airborne route of Ebola virus infection has been used to deliberately infect non-human primates (NHPs). It is possible and it can be done. Okay? I'm not covering up any secret knowledge or trying to conceal facts that only we few evil-society-of-science types know. I don't secretly work for an agency aiming to delude you dear readers into feeling falsely safe about the risks associated with being near an Ebola virus infected person (which most reading this will likely never be). Frankly, I'm learning this as I go.

Don't expect perfection from risk mitigation advice.

Like all things that involve biology, there are hardly ever clear-cut lines and yes or no definitions and explanations. Sometimes that's because things vary...because biology! Sometimes that's because we haven't yet done enough science to know those answers. I'm not an expert on ebolaviruses nor on Ebola virus disease (EVD) - but in my time learning about the viruses and the disease, its clear that this is (yet another) area that is lacking in all sorts of information. So risks are judged using what we do know and can support and verify, with softer language used when decision makers don't know for certain; less so when they think they do.

When that message of risk gets passed to the public, it is important to be accurate, clear, concise but not to over-simplify things because that may degrade trust in the body(s) sending the message if things change later. That's a very tough balance when dealing with biological risks.

So having said that, let's talk pigs.

Pigs are not primates.

In ebolaville - the virtual world created by social and mainstream media stories and discussion about ebolaviruses - a lot of people have been throwing the 2012 pig to macaque study (8) around as an argument for why we should admit that ebolaviruses spread by an airborne route and run for the hills. This is why that is not a good comparison:

Pigs have a different disease and replication process to humans.

Pigs tend to have much more virus growing in their lungs.(12)
Pigs tend to cough and sneeze and generally propel more of said pathogen from their lungs.(11)

Pigs may eject more infectious viruses in their droplets than do primates

If we look at the study of disease occurrence and spread in previous outbreaks, that epidemiology does not suggest an airborne spread - the numbers and nature of human-to-human spread don;t show it as any sort of major contributor to spread. Might it be a minor contributor? Possibly. We don;t know either way with 100% surety. But we do know some other things. One of these is that it takes very little virus to infect pigs and NHPs. If there are not obvious signs of an airborne spread in humans, we just not have detected it yet or, it may have a biological basis. It is possible that the infectious dose (amount of virus needed to get a foothold and start an infection) may be much higher for humans; infected and severely ill human cases may not breathe out infectious virus or ebolaviruses may not survive for long in the aerosols expired by humans,(19) even if they can survive on hard surfaces or in generated aerosols under laboratory conditions.(20)

Non-human primates can be infected with ebolaviruses via a lab-made aerosol with lots of lab virus at lab temperatures and lab humidity and other lab conditions in a lab.

You get that this is done in a lab? Cool.

It apparently does not take much virus to infect a human via an aerosol according to the Public Health Agency of Canada's (PHAC) Pathogen Safety Data Sheet (PSDS) on ebolavirus.(1) Only 1-10 infectious organisms (see above). But one problem with that PSDS is that it cites only 1 paper to support that range. Ref 21 from the PSDS is entitled Clinical recognition and management of patients exposed to biological warfare agents.(2) It is 1997 review that does not specify if this range is specific to any 1 or more of the ebolaviruses, just "viral hemorrhagic fevers". The PSDS seems to rely on that 1 line. In that reference, there are no further links to studies that define this range for humans, ebolaviruses or an Ebola virus (EBOV) of the species Zaire ebolavirus. I've sent a couple of emails in the past week, seeking further clarification from ebolavirus experts, but have yet to hear anything back.

In a laboratory experiment reported in 1995, transmission of an EBOV from one set NHPs infected by injection, to another set resulted in 2 of 3 NHPs (1 with a heavy load of virus in the lung) becoming infected and that seemed to have occurred through some kind of airborne route as the 2 groups of animals were separated by 3m and care was taken to avoid creating bigger droplets and splashes during cage cleaning.(15) While the authors noted that fomites (contaminated objects and surfaces) or contact droplet transmission of virus was unlikely, the exact mode of transmission to the second group of NHPs could not be determined. In a follow-up study, the authors were able to prove that conjunctival and oral exposure to an EBOV could indeed result in infection in NHPs.(18) Thus we have plenty of reason for the use of masks, goggles and face shields that are already part of the recommended personal protective equipment (PPE) items for dealing with infected humans.

However, there are a number of issues related to forced aerosol infection of NHPs, many of which can be found in a massive and detailed 2008 review by Dr. Jens Kuhn.(3) These include:

Often unrealistically high viral loads - the exact amount of infectious virus humans are exposed to during outbreaks has not been defined.
Temperature and humidity conditions that were unlikely to reflect conditions during outbreaks in Africa - but may reflect conditions in hospitals.
An initially lung-focussed pattern of viral replication (7) results from direct aerosol delivery of virus to NHP airways which seems different to infection of humans via the more frequent natural direct contact route. Systemic spread to multiple organs then follows via infected dendritic cells and macrophages and blood monocytes.
Different routes of virus acquisition can lead to different incubation periods.
Different virus isolates, sources and preparations may affect the course of infection and disease
Because of the small and enclosed space and air throughput in head-only chambers, droplets rather than droplet nuclei may be the vehicle carrying infectious virus. This is important because, as you can read in the companion piece, droplet nuclei are the component of a lingering "airborne route" of acquisition and if NHPs are in fact infected by the droplets, that may be more indicative of direct fluid contact than true airborne travel.

A head-only inhalation chamber of the sort used in NHP
aerosol inoculation studies. Biaera Technologies.
Image from http://www.biaera.com/our-technology/peripheral-
aerosol-instruments/head-only-chamber/. See also (17)
Click on image to enlarge.

Some NHP studies that have successfully caused initial respiratory infection using an airborne route to infect NHPs under controlled experimental conditions include the following:

1,000 plaque forming units (PFU; a measure of how much virus is in a preparation using cell culture methods in the lab) of either a Kikwit EBOV isolate or a Boniface isolate of Sudan virus (SUDV; species Sudan ebolavirus) isolate were delivered using a Collison nebulizer (producing small droplets) after intramuscular immunization with a recombinant adenovirus vaccine.(5)
1,000 PFU of a Kikwit EBOV isolate was delivered with a Collision nebulizer via a head-only aerosol chamber, after intramuscular immunization with a recombinant vesicular stomatitis virus (VSV) vaccine.(6)
743-274,000 PFU of a Kikwit EBOV isolate was delivered to with a Collision nebulizer via a head-only aerosol chamber, to examine aerosol-related pathology.(7)
~50 or ~500 PFU of a Boniface SUDV isolate were delivered to 3 different NHP species using a Collison nebulizer via a head-only chamber to compare species-specific effects.(14)
0.8-128 PFU of a Kikwit EBOV isolate was delivered to 3 different NHP species using a Collision nebulizer via a head-only aerosol chamber, to examine disease course between species.(9)
~300-50,000 PFU of an EBOV isolate was delivered to with a Collision nebulizer (0.8-1.2um droplets) via a head-only aerosol chamber, to examine aerosol-related pathology.(16)

Are primates humans?

Judging by the effort we put into getting rid of our fur compared to an NHP, I'd say we're not!

But on the topic of EVD, some NHPs that we infect with an ebolavirus, show very similar disease signs, symptoms and disease progression to those of EVD in humans; especially rhesus macaques [Macaca mulatta] although oneo f the studies above showed that 3 different NHP species were not that different in the way they responded to infection (rhesus macaques as well as cynomolgous macaques [Macaca fascicularis] and African green monkeys [Chlorocebus aethiops]).(9)

Rhesus macaques become febrile, anorexic, lethargic, viraemic, develop a rash and sometimes develop diarrhoea and melena (gastrointestinal bleeding).(3)

But no animal model seems to completely capture other components of human disease which have historically included conjunctivitis, diarrhoea and vomiting and coughing up blood. Vomiting up blood and having bleeding gums occurs more often in fatal cases than in survivors.(3)

Bleeding only occurred in 41% of 103 observed human patients during the 1995 Kikwit outbreak of an EBOV.(3)

So the answer is, primates are not humans when it comes to EVD, but they are pretty close. Yet within that "pretty close" lies an immeasurable amount of variation that may mislead when trying to map the course of NHP disease onto that of humans.

Where does that leave us?

I admit to being very uneasy saying that there is no risk at all of an airborne route of ebolavirus infection. Clearly it can be forced to happen, but we have no evidence that it has ever happened in humans in an outbreak. But let's put that into context. An absence of evidence is not evidence of absence. Outbreaks of ebolaviruses are not particularly conducive to large careful research projects measuring infectious droplet nuclei around critically ill people, especially when the occur in exotic locations in someone else's back yard.

So have I deserted by position from yesterday's post stating no airborne role for ebolavirus transmission between humans? No, not at all. What we know is that the overwhelming majority of human EVD cases acquire their infection during the time they are in direct contact with the fluids of a very ill EVD case; be that through physical contact or wet droplet spray impact. Beyond that fact, it may just be a discussion based on academic musings and hand-waving. But it is a discussion we should be having a little more I feel. A back-and-forth rather than messages with guarantees and statements dealing in black and white absolutes. I'm not sure the public believe in or feel safer with such absolutes today. We're all a bit too cynical for that.

If infection can happen between primates via the air, it is a very, very inefficient process as a study of 78 people from 27 households with EVD cases during the 1995 Kikwit revealed.(10) Those 78 household members had no physical contact with the cases, and they did not get sick. Others who had physical contact, got EVD.

In a recent study by the authors of the 2012 pig/macaque study we started this post with, infected NHPs did not pass EBOV to uninfected NHPs only 30cm away.[21] Not only was there no disease in the inoculated animals but no antibodies were detectable in the uninfected NHPs 4-weeks later. There had been no infection at all.

While at some point we'll need to be more sure of all this for humans than we are now, we can say that pigs aren't primates and airborne route has not been shown to be a risk for human acquisition of an EBOV.

References..

Friday, 15 August 2014

Ebola virus may be spread by droplets, but not by an airborne route: what that means

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