Showing posts with label Zaire ebolavirus. Show all posts
Showing posts with label Zaire ebolavirus. 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...

  1. https://twitter.com/WHO/status/863022054223773697 
  2. https://www.theatlantic.com/science/archive/2017/05/a-new-ebola-outbreak-in-the-democratic-republic-of-congo/526506/ 
  3. http://www.npr.org/sections/thetwo-way/2017/05/12/528124232/ebola-death-confirmed-in-democratic-republic-of-congo 
  4. https://www.wired.com/2017/05/ebola-returns-central-africas-virus-hunters-ready/ 
  5. https://foreignpolicy.com/2017/05/12/ebola-returns-in-congo-a-test-of-next-time/ 
  6. www.minisanterdc.cd 
  7. http://www.who.int/csr/don/13-may-2017-ebola-drc/en/ 
  8. http://www.mysanantonio.com/news/local/article/New-Ebola-case-reported-in-Democratic-Republic-of-11143890.php?cmpid=twitter-tablet 
  9. http://www.sciencemag.org/news/2017/05/will-vaccine-help-curb-new-ebola-outbreak-drc 
  10. http://www.nature.com/news/ebola-vaccine-could-get-first-real-world-test-in-emerging-outbreak-1.21989 
  11. http://www.afro.who.int/en/media-centre/pressreleases/item/9609-dr-moeti-in-kinshasa-to-discuss-reponse-to-ebola-outbreak.html 
  12. http://www.reuters.com/article/us-health-ebola-congo-idUSKCN18A0ZP
  13. https://www.newscientist.com/article/2131131-ebola-once-again-on-the-prowl-as-emergency-teams-stand-ready/
  14.  http://reliefweb.int/report/democratic-republic-congo/ebola-virus-disease-democratic-republic-congo-external-situation-0
  15. http://www.afro.who.int/en/media-centre/pressreleases/item/9631-drc-response-to-the-ebola-virus-disease-outbreak-in-bas-uele.html
  16. http://www.radiookapi.net/2017/05/15/actualite/sante/ebola-en-rdc-defis-et-chances-dun-lointain-enclavement 
  17. http://apps.who.int/iris/bitstream/10665/255486/1/EbolaDRC-1752017-eng.pdf?ua=1 
  18. http://www.healio.com/infectious-disease/emerging-diseases/news/online/%7Bf835f3ce-da12-4ae7-9c8c-0e0f3d6ef8f3%7D/extent-of-ebola-outbreak-in-drc-may-not-be-known-for-weeks

Maps used to help place Likati and Bas-Uele...
      Updates...
      1. Fixed spelling mistakes in Likati, added detail about sampling delays
      2. Added references 10-12; noted 2 cases now confirmed, 19 suspect cases in total 
      3. Update on where the 300,000 vaccines come from [13]
      4. Update on contacts and ReliefWeb and WHO references
      5. New SitRep from WHOAfro - altered case & testing numbers
      6. Replaced maps to add in the correct population!

      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

      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..


        1. http://www.who.int/mediacentre/news/ebola/24-october-2014/en/
        2. http://www.bbc.co.uk/news/world-africa-29755443

        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.

        Blood...

        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]

        Sweat...

        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.
        Tears...

        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
        Spit...
        • 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]
        References...
        1. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2395567/pdf/bullwho00439-0113.pdf
        2. http://www.ncbi.nlm.nih.gov/pubmed/8712894
        3. http://www.ncbi.nlm.nih.gov/pubmed/9278608
        4. http://link.springer.com/article/10.1007/BF01734141
        5. http://www.sciencemag.org/content/suppl/2014/08/27/science.1259657.DC1/Gire.SM.pdf
        6. http://www.nature.com/nature/journal/vnfv/ncurrent/pdf/nature13777.pdf
        7. http://www.ncbi.nlm.nih.gov/pubmed/16652308
        8. http://www.ncbi.nlm.nih.gov/pubmed/9988163


        Saturday, 30 August 2014

        The fifth I give you...[UPDATED]

        Senegal. 
        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.

        References...
        1. http://in.reuters.com/article/2014/08/29/us-health-ebola-senegal-idINKBN0GT1CD20140829?feedType=RSS&feedName=health&utm_source=dlvr.it&utm_medium=twitter&dlvrit=309303
        2. http://edition.cnn.com/2014/08/29/health/ebola-outbreak-senegal/
        3. http://www.washingtonpost.com/news/world/wp/2014/08/29/the-ebola-virus-has-spread-to-senegal-as-the-deadliest-outbreak-in-history-gets-worse/
        4. http://www.washingtonpost.com/world/africa/alarm-grows-as-ebola-outbreak-spurs-more-flight-cancellations-border-closures/2014/08/25/87e6d020-2c66-11e4-994d-202962a9150c_story.html
        5. http://www.bbc.com/news/world-africa-28893835
        6. http://fox59.com/2014/08/22/senegal-closes-its-borders-with-guinea-over-ebola-fears/
        7. https://www.internationalsos.com/ebola/index.cfm?content_id=434&language_id=ENG



        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 Minister for Health, 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 the puzzle.

        References
        1. http://virologydownunder.blogspot.com.au/2014/08/behind-naming-of-ebola-virusesnot-yet.html
        2. http://www.aljazeera.com/news/africa/2014/08/congo-ebola-outbreak-2014824183430461469.html
        3. http://en.wikipedia.org/wiki/File:Hammer-headed_Bat_area.png
        4. http://www.iucnredlist.org
        5. http://en.wikipedia.org/wiki/Hammer-headed_bat
        6. http://www.afro.who.int/en/clusters-a-programmes/dpc/epidemic-a-pandemic-alert-and-response/outbreak-news/4263-ebola-virus-disease-drc.html
        7. http://reliefweb.int/report/democratic-republic-congo/update-ebola-virus-disease-drc-no-5-30-august-2014
        8. http://www.who.int/mediacentre/news/ebola/2-september-2014/en/
        9. http://reliefweb.int/report/democratic-republic-congo/virological-analysis-no-link-between-ebola-outbreaks-west-africa
        10. http://virologydownunder.blogspot.com.au/2014/08/behind-naming-of-ebola-virusesnot-yet.html

        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...
        1. http://www.who.int/mediacentre/factsheets/fs103/en/
        2. http://ecdc.europa.eu/en/healthtopics/ebola_marburg_fevers/factsheet-for-health-professionals/Pages/factsheet_health_professionals.aspx
        3. http://www.phac-aspc.gc.ca/lab-bio/res/psds-ftss/ebola-eng.php
        4. http://www.usamriid.army.mil/education/bluebookpdf/USAMRIID%20BlueBook%207th%20Edition%20-%20Sep%202011.pdf
        5. http://jid.oxfordjournals.org/content/196/Supplement_2/S142.full
        6. http://jid.oxfordjournals.org/content/179/Supplement_1/S170.long
        7. http://www.ncbi.nlm.nih.gov/pubmed/9988162
        8. http://www.ncbi.nlm.nih.gov/pubmed/890413

        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..
        1. http://www.phac-aspc.gc.ca/lab-bio/res/psds-ftss/ebola-eng.php#note21
        2. http://www.ncbi.nlm.nih.gov/pubmed/9244332
        3. http://www.ncbi.nlm.nih.gov/pubmed/18637412
        4. http://www.ncbi.nlm.nih.gov/pubmed/9988155
        5. http://www.ncbi.nlm.nih.gov/pubmed/20181765
        6. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3398796/pdf/nihms390624.pdf
        7. http://vet.sagepub.com/content/50/3/514.long
        8. http://www.nature.com/srep/2012/121115/srep00811/full/srep00811.html
        9. http://www.ncbi.nlm.nih.gov/pubmed/21651988
        10. http://jid.oxfordjournals.org/content/179/Supplement_1/S87.long
        11. https://www.sciencenews.org/article/airborne-transmission-ebola-unlikely-monkey-study-shows
        12. http://www.vox.com/2014/8/10/5980553/ebola-outbreak-virus-aerosol-airborne-pigs-monkeys/in/5712456
        13. http://www.nature.com/srep/2014/140725/srep05824/full/srep05824.html
        14. http://www.ncbi.nlm.nih.gov/pubmed/23202456
        15. http://www.ncbi.nlm.nih.gov/pubmed/8551825
        16. http://www.ncbi.nlm.nih.gov/pubmed/7547435
        17. http://www.mdpi.com/1999-4915/4/8/1305/htm
        18. http://www.ncbi.nlm.nih.gov/pubmed/8712894
        19. http://www.ncbi.nlm.nih.gov/pubmed/15588056
        20. http://www.ncbi.nlm.nih.gov/pubmed/20553340
        21. http://www.ncbi.nlm.nih.gov/pubmed/25059478

        Friday, 15 August 2014

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

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

        You can get to this specific post by clicking on the link below...

        https://virologydownunder.com/flight-of-the-aerosol/

        Please adjust your bookmarks.

        Apologies for any inconvenience.

        Friday, 4 July 2014

        Ebola virus disease (EVD) 2014 West African outbreak..

        I will update this static page (link won't change so you can bookmark it) with the 2014 West African Ebola virus disease (EVD) numbers after they are released by the World Health Organization (WHO). The date these graphs were last updated is listed at the top of the first panel or "dashboard" of graphs an totals .

        The WHO create multi-page Situation Reports [2] and brief Situation Summaries.[3] The SitRep's are currently presented on Wednesday and "additional updated figures" will be posted" a SitSumm when they become available any day of the week" (via eMail to journalists from WHO).


        My totals include all
         countries that have hosted a case in, or sourced from, a West African nation. Countries include Guinea, Liberia, Sierra Leone, Nigeria (now EVD-free), Senegal (now EVD-free), the United States of America, Spain (now EVD-free), Mali (now EVD-free) and the United Kingdom. 'EVD-free means there are no known cases of EVD in the country. Some countries bring in cases of EVD to treat them; they can be defined as free of Ebola virus transmission, but not technically free of the EVD.









        The West African region epidemic (top map below), including countries with imported cases and the totals from past Ebola virus disease outbreaks and the few imported monkey cases (the US & Philippines [hence zero human cases]) plotted by total numbers and country (bottom map).




        A note about the proportion of fatal cases (PFC): On these graphs, my PFC calculations for West African countries and the DRC are based on dividing the total number of suspected+probable+confirmed deaths by the number of total suspected+probable+confirmed cases on the same date. This is crude and is an underestimate of the true case fatality ratio (CFR) which has stood at ~70% throughout the epidemic.[2]

        Reminders: 

        • The graphs above, as with all made by me VDU, are made for general interest only. It is also freely available for anyone's use, just cite the blog (http://virologydownunder.blogspot.com.au/) and me (Dr. Ian M Mackay, PhD) please. 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. 
        • Sometimes there are very country-specific differences in what gets presented to/via the World WHO DONs/SitReps which make this process less clear than it could be. I recommend you have a read and compare the data from each of the countries for yourself to understand these issues.
        • As I've talked about previously,[1] these numbers are all volatile for a variety of reasons, some Ebola-specific, so regard this chart for its trends only.
        • I am only able to plot what is publicly available. To date, this does not include granular data with dates of onset, or daily data of any kind. The WHO have these data and you will see them become more available through their Situation Reports found here http://www.who.int/csr/disease/ebola/situation-reports/en/ 
        1. References... 
          1. Ebola virus disease and lab testing...
            http://virologydownunder.blogspot.com.au/2014/04/ebola-virus-disease-and-lab-testing.html
          2. Ebola virus disease outbreak Situation Reports (SitRep)
            http://apps.who.int/ebola/en/current-situation
          3. Ebola virus disease outbreak Situation Summaries (SitSumm)
            http://apps.who.int/gho/data/view.ebola-sitrep.ebola-summary-latest?lang=en