Archive for the ‘Ebola’ Category

Anyone interested? A candidate virology textbook…

28 July, 2015

I would like to test the response to a Introduction to Virology ebook that I want to develop from my extant Web-based material, given that this is likely to disappear soon with our Web renewal project here at UCT.

Virus_Picture_Book_copy_iba

Download the Virus Picture Book excerpt here. And then please tell me what you think / whether you would buy one (projected price US$15 – 20)?  Ta!

Ebola on the Web – 20 years on

21 July, 2015

I have already done a partial retrospective on having been reporting on Ebola haemorrhagic fever viruses for just over 20 years – but I totally forgot to commemorate that I have been producing Web pages for just over 21! So I’m going to go on a nostalgic ramble through the past, mainly using Ebola as the vehicle, and highlighting some of the history of virology along the way.

By the way, I HAVE to commend the Wayback Machine here: I have also previously bemoaned the fact that Web pages are NEVER preserved by their creators at regular intervals – but this is exactly what they do.  From 1997 onwards in the case of the whole of the University of Cape Town’s site and mine as part of that – and how interesting it has been to go back and look at what I thought was cool then!  But actually, what’s not to like? I mean, there’s hepatitis G, Congo fever, smallpox, Ebola, “equine morbillivirus” (aka Hendra virus) – and life on Mars. Or not B-)

What’s interesting, though, is that they have preserved almost all of my Ebola news pages – dating from May 1995, from right near the onset of the Kikwit Ebola epidemic.  There’s all sorts of interesting stuff there – though with some holes, caused by Lost Pages – ranging from a discussion of the possibility of finding Ebola in cotton plants [not!], with my old friend Murilo Zerbini, to a thread on “Candidate for the Ebola Reservoir Organism” from the late lamented bionet.virology discussion group, to whether Ebola Reston was airborne (probably not).

Great historical stuff, right there – and thank deities it is preserved via Wayback, because our upcoming Web renewal project here at UCT will kill ALL links from our Departmental site.  Get it while you can!

And while we’re at it: here’s a useful list of all Ebola-related posts on ViroBlogy since 2011.  Note when the first mention of plant-made antibodies to Ebola virus was….

Molecular evidence of Ebola Reston virus infection in Philippine bats

18 July, 2015

The Discovery of Filoviruses

Ebola virus mutating, scientists say

29 January, 2015

First Ebola case linked to bat play – really?

30 December, 2014

Ethical dilemma for Ebola drug trials

13 November, 2014

Rabies Vaccine Protects Nonhuman Primates against Deadly Ebola Virus

26 October, 2014

Packs of wild dogs spread Ebola after eating corpses!! Or…not, maybe?

13 October, 2014

Norway to get world’s last dose of ZMapp – update

8 October, 2014

8 September, 2014

20 years on, and here we are with Ebola, again

25 August, 2014

5 Viruses That Are More Frightening Than Ebola

20 August, 2014

What Would Happen if You Got Ebola?

13 August, 2014

Plant-made antibodies used as therapy for Ebola in humans: post-exposure prophylaxis goes green!

5 August, 2014

Has the Time Come to Test Experimental Ebola Vaccines?

30 July, 2014

Plant-Based Antibodies, Vaccines and Biologics 5, Part 5

3 September, 2013

Ebola Outbreak in Uganda: CDC Rushes to Contain Virus

8 August, 2012

More Ugandans Admitted with Possible Ebola

1 August, 2012

Ebola reaches Uganda’s capital

31 July, 2012

31 July, 2012

Canadian researchers thwart Ebola virus

14 June, 2012

African monkey meat that could be behind the next HIV

25 May, 2012

Current Opinion in Virology – Mass extinctions, biodiversity and mitochondrial function: are bats ‘special’ as reservoirs for emerging viruses?

5 April, 2012

When dinner could kill you: smoked chimpanzee, anyone?

14 January, 2012

Virology Africa 2011: viruses at the V&A Waterfront 2

19 December, 2011

Ebola: ex tobacco, semper a vaccine novi

6 December, 2011

The guru speaks: new eBooks on viruses!

24 June, 2015

I have to thank my long-time digital media guru, Alan J Cann, for reviewing our humble eBook offerings in MicrobiologyBytes.  You good man!  Much appreciated, and it will not have escaped our attention that this endorsement may actually result in sales.  If so, a glass or three of the finest red is yours if you come to these shores, good sir B-)

The Discovery of Filoviruses

10 March, 2015

The discovery of filoviruses: Marburg and Ebola

Marburg virus

In 1967, the world was introduced to a new virusthirty-one people in Marburg and Frankfurt in Germany, and Belgrade in the then Yugoslavia, became infected in a linked outbreak with a novel haemorrhagic fever agent. Twenty-five of them were laboratory workers associated with research centres, and were directly infected via contact with infected vervet monkeys (Chlorocebus aethiops) imported to all three centres from Uganda.  Seven people died.   In what what was a remarkably short period of time for that era – given that this was pre-sequencing and cloning of nucleic acids, let alone viruses – it took less than three months for scientists from Marburg and Hamburg to isolate and characterise what was being called “green monkey virus” virus. The new agent was named Marburg virus (MARV), after the city with the greatest number of cases.

The first electron micrograph of the virus clearly exhibits the filamentous nature of the particles, complete with the now-famous “shepherd’s crook”.

The virus disappeared until 1975, when an Australian hitchhiker who had travelled through what is now Zimbabwe was hospitalised in Johannesburg, South Africa, with symptoms reminiscent of Marburg disease. He died, and his female companion and then a nurse also became infected with what was suspected to be yellow fever or Lassa viruses. In an example for later outbreaks, this led to rapid implementation of strict barrier nursing and isolation of the patients and their contacts, which resulted in quick containment of the outbreak – with recovery of the two secondary cases. MARV was later identified in all three patients.

Ebola virus

Ebola viruses burst from obscurity in 1976, with two spectacular outbreaks of severe haemorrhagic fever in people – both in Africa. In the better-known outbreak for which the viruses were later named, Ebola virus (EBOV) was first associated with an outbreak that eventually totalled 318 cases, starting in September 1976.  This was in the Bumba Zone of the Equateur Region in the north of what was then Zaire, and is now the Democratic Republic of the Congo (DRC).  The index case in the outbreak, as well as many of those subsequently infected, was treated in the Yambuku Mission Hospital. He was injected with chloroquine to treat his presumptive malaria: within a few days fever symptoms developed again; within a week, several others who had received injections around the same time also developed fevers which in several cases had haemorrhagic complications. 

Interestingly, women 15-29 years of age were most affected by the disease: this was strongly correlated with their attending antenatal clinics at the hospital, where they regularly received injections.

Apparently the hospital had only five old-style syringes and needles, and these were reused without proper sterilisation.  Nearly all cases in this outbreak either received injections at the hospital, or had close contact with those who had. 

Most people were infected within the first four weeks of the outbreak, after which the hospital was closed because 11 of 17 staff had died.  Another  269 people died, for a total estimated case-fatality rate of 88%.

The incubation period for needle- transmitted Ebola virus was 5 to 7 days and that for person to person transmitted disease was 6 to 12 days.

Interestingly, in post-epidemic serosurveys in DRC, antibody prevalence to the “Zaire Ebola virus” has been 3 to 7%: this indicates that subclinical infections with the disease agent may well be reasonably common.

The team that discovered the virus at the Antwerp Institute of Tropical Medicine in Belgium, did so after receiving blood samples in September 1976 from a sick Belgian nun with haemorrhagic symptoms who had been evacuated from Yambuku to Kinshasa in the DRC, for them to investigate a possible diagnosis of yellow fever.  Following her death, liver biopsy samples were also shipped to Antwerp – where the team had already ruled out yellow fever and Lassa fever.  Because of the severe nature of the disease, and its apparently novel agent, the World Health Organisation (WHO) arranged that samples be sent to other reference centres for haemorrhagic viruses, including the Centres for Disease Control (CDC) in Atlanta, USA.

The Belgian team were the first to image the virus derived from cell cultures on an electron microscope – when it was obvious that the only thing it resembled was Marburg virus. 

Image copyright CDC / Frederick A Murphy, 1976

Image copyright CDC / Frederick A Murphy, 1976

The CDC quickly confirmed that it was Marburg-like, with possibly the most famous virus image in the world, but that it was a distinct and new virus.

This meant it needed a name – and it was given one derived from the Ebola River that was supposed to be near the town of Yambuku.

Google map of the area where the first Ebola haemorrhagic fever outbreaks occurred

Google map of the area where the first Ebola haemorrhagic fever outbreaks occurred

Another, minor outbreak of the virus occurred in June 1997 in Tandala in north-western DRC: one young child died, and virus was recovered from her – and subsequent investigations showed that “two previous clinical infections with Ebola virus had occurred in 1972 and that about 7% of the residents had immunofluorescent antibodies to the virus”. This further reinforced the idea that subclinical infections were possible.

Sudan virus

In June 1976 – before the Yambuku epidemic in DRC –  an outbreak of a haemorrhagic fever began in the southern Sudanese town of Nzara.  The presumed index case was a storekeeper in a cotton factory, who was hospitalised on June 30th, and died within a week.

There were a total of 284 cases in this outbreak: there were 67 in Nzara, where it is presumed to have originated, and where infection spread from factory workers to their familes.  There were also 213 in Maridi, a few hours drive away – where, as in Yambuku, the outbreak was amplified by “nosocomial” or hospital-acquired transmission in a large hospital. In this case, transmission seems to have been associated with nursing of patients.  The incubation period in this outbreak was 7 – 14 days, with a case mortality rate of 53%.

Two viral isolates were made from sera from Maridi hospital patients in November 1976. Antibodies to the now-identified “Ebola virus” from DRC were detected in 42 of 48 patients clinically-diagnosed patients from Maridi – but in only 6 of 31 patients from Nzara.  However, it was subsequently shown that the Sudan and DRC Ebola viruses were different enough from one another to be separate viral species (see later), which undoubtedly affected the results.

Interestingly, 19% of the Maridi case contacts had antibodies to the virus – with very few of them with any history of illness.  This strongly indicates that the Sudan virus can cause mild or even subclinical infections.

An indication of the possible origin of the epidemic is the fact that 37% of the workers in the Nzara cotton factory appeared to have been infected, with 6 independently-acquired infections – and that this was concentrated in the cloth room, where there were numerous rats as well as thousands of insectivorous bats in the roof.  However, subsequent study of antibodies in the bats failed to detect evidence of infection, and no virus was isolated from bat tissue.

There was another outbreak of the same type of Ebola haemorrhagic fever in the area of Nzara in July – October 1979: this resulted in 34 cases, 22 of them fatal, with the index patient working at the cotton factory and all others being infected via the hospital he was admitted to.  It is interesting that antibodies to the Sudan virus were detected in 18% of adults not associated with the outbreak, leading the report’s authors to speculate that the virus was endemic in this region.

It was thought that the Sudan and DRC outbreaks were linked: the original WHO Bulletin report on the Sudan outbreak even speculates that extensive truck-borne commercial goods traffic between Bumba in DRC and Nzara in what is now South Sudan could have caused the DRC outbreak.  However, comparisons between the viruses isolated from the two epidemics later showed that they were distinct, both in terms of virulence, and antigenicity – meaning the Sudan virus got its own name.

Epidemics and outbreaks have resulted from person to person transmission, nosocomial or in-hospital spread, or laboratory infections. The mode of primary infection and the natural ecology of these viruses are unknown. Association with bats has been implicated directly in at least 2 episodes when individuals entered the same bat-filled cave in Eastern Kenya. Ebola infections in Sudan in 1976 and 1979 occurred in workers of a cotton factory containing thousands of bats in the roof. However, in all early instances, study of antibody in bats failed to detect evidence of infection, and no virus was isolated form bat tissue.

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Ebola virus mutating, scientists say

29 January, 2015

Scientists at the Institut Pasteur in France who are tracking the Ebola outbreak in Guinea say the virus has mutated.

Source: www.bbc.com

I would be surprised it there weren’t evidence by now of adaptation to humans: never in any previous outbreak of EHD [Ebola haemorrhagic disease] has the person-person chain of transmission been sustained for so long, meaning never before has there been the opportunity for human-specific adaptations to become established.

The article points out that on consequence of mutation may be that the virus becomes less virulent, leading to a greater incidence of asymptomatic infection – of which there is already evidence from previous outbreaks, and which has been implicated in the lessening incidence of transmission because of increasing herd immunity.

However, this same property might lead to increased transmission to the non-exposed, because of a lack of signs that contacts with the infected person(s) should be avoided – and for a disease as lethal as EHD, even a reduced mortality rate still means you should avoid it at all costs.

The idea of developing a modified live measles virus vaccine as an Ebola virus vaccine vector, which is what the Institut Pasteur is apparently doing, seems to be a very good one.  Measles is still a major potential problem in that part of the world, necessitating regular infant immunisations, and coupling anti-measles with an anti-Ebola vaccine in those countries is probably very good use of both a proven vaccine and existing EPI infrastructure.

 

See on Scoop.itVirology News

Ethical dilemma for Ebola drug trials

13 November, 2014

Public-health officials split on use of control groups in tests of experimental treatments.

With clinical trials of experimental Ebola treatments set to begin in December, public-health officials face a major ethical quandary: should some participants be placed in a control group that receives only standard symptomatic treatment, despite a mortality rate of around 70% for Ebola in West Africa?

Two groups planning trials in Guinea and Liberia are diverging on this point, and key decisions for both are likely to come this week. US researchers meet on 11 November at the National Institutes of Health (NIH) in Bethesda, Maryland, to discuss US-government sponsored trials. A separate group is gathering at the World Health Organization (WHO) in Geneva, Switzerland, on 11 and 12 November to confer on both the US effort and trials organized by the WHO with help from African and European researchers and funded by the Wellcome Trust and the European Union.

Source: www.nature.com

I have to say – faced with a deadly disease, I think it is UNethical to have control / placebo arms of any trial.

Seriously: what about comparing ZMapp and immune serum, for example, with historical records of previous standard of care outcomes rather than directly?

I know if I were an Ebola patient, and I saw someone else getting the experimental therapy and I didn’t, that I would have a few things to say.

It’s not as if these therapies have not been tested in primates, after all – in fact, both the ChAd3 and MVA-based vaccines and ZMapp have been thoroughly tested in macaques, as have the other therapeutics, with no adverse events there.

I say if people say clearly that they want an experimental intervention, that they should get one: after all, the first use of immune serum was not done in a clinical trial, but rather as a last-ditch let’s-see-if-this-works intervention – yet its use does not seem controversial?

See on Scoop.itVirology News

Virology Africa 2015: consider yourselves notified!

7 November, 2014

Dear ViroBlogy and Virology News followers:

Anna-Lise Williamson and I plan to have another in our irregular series of “Virology Africa” conferences in November-December 2015, in Cape Town.

As previously, the conference will run over 3 days or so, possibly with associated workshops, and while the venue is not decided, we would like to base it at least partially in the Victoria & Alfred Waterfront.

We also intend to cover the whole spectrum of virology, from human through animal to plant; clinical aspects and biotechnology.

We intend to make it as cheap as possible so that students can come. We will also not be inviting a slate of international speakers, as we have found that we always get quite an impressive slate without having to fund them fully.

It is also the intention to have a Plant Molecular Farming workshop – concentrating on plant-made vaccines – concurrently with the conference, in order to leverage existing bilateral travel grants with international partners. If anyone else has such grants that could be similarly leveraged, it would be greatly appreciated.

See you in Cape Town in 2015!

Ed + Anna-Lise

ZMapp in an HIV context

30 October, 2014

It was truly a pleasure to run into Kevin Whaley of Mapp BioPharmaceutical today, here at the HIVR4P inernational conferrence in Cape Town – so I made him come and have coffee with me and Anna-Lise, so we could chat about molecular farming.
Of course, it is the ZMapp plant-made therapeutic antibody that has set the molecular farming world alight, that was the main topic. Apparently Mapp is looking at a January 2015 date for a clinical trial in the affected West African countries, alongside the adenovirus and RSV-vectored vaccines. The plants for the production of the thousands of doses that will be needed – and recall, that’s a couple of grams per dose at 50 mg/kg – are already growing at Kentucky Bioprocessing in Louisville, so one imagines that a pile of work will be coming their way in the near future.
It’s also sobering to realise that even though plants ARE a more scalable and POTENTIALLY cheaper means of production of biologics, that therapeutic antibody production in particular, MAY be better suited right now to conventional technologies, such as CHO cell or even fungal production.
This is because large quantities of MAbs will be needed, and there is established capacity for production of hundreds of thousands of litres of cell culture right now, and yields and production costs have been driven right down to US$10 / gram for MAbs already, according to Kevin.
This partly answers a question I had during the HIVR4P sessions: if one is to use 20-50 mg/kg dosages for anti-HIV neutralising MAbs such as VRC01, how would it be remotely possible to make the amounts required for use in a developing country setting, where the patient can almost definitely NOT pay?
I still think there is a role for plants – but maybe this will be in the area of prophylactic use of MAbs, where much lower doses may be effective because there is not nearly as much virus to neutralise or inactivate.
And of course, Mapp is involved here too, with plant-made VRC01 in particular being incorporated into microbicides.
A great bunch of people, with really noble aims.

Rabies Vaccine Protects Nonhuman Primates against Deadly Ebola Virus

26 October, 2014

The research team is pursuing the inactivated rabies/Ebola vaccine for use in humans. The live vaccine is being developed for use in protecting wildlife at risk of Ebola virus infection in Africa, which could also serve to prevent transmission into the human population.

Source: www.niaid.nih.gov

I missed this one at the time – and it is an interesting piece of news.  Basically, the research team cloned the Ebola envelope glycoprotein GP1 into the extant rabies virus vaccine strain genome, and tested a live version, a replication-deficient version, and a killed whole virion version in macaques.

Their results are interesting enough – 100% protection against challenge for live, 50% for the other two – that they plan to follow up to see whether or not additional doses could improve protection in the two non-replicating versions, and to make a “multivalent filovirus vaccine”.

This can only be welcome news against the backdrop of the still-ongoing epidemic in West Africa – where two other vaccines (recombinant vesicular stomatitis and chimpanzee adenovirus) are probably going to be trialled next year. The rabies version at least is based on a very well characterised vaccine that already protects against an extremely deadly disease – it remains to be seen how well the other two do.

I forgot to mention that I found reference to this article on “The Zombie Research Society”‘s blog site: http://zombieresearchsociety.com/archives/25562. A very apt place if one considers the parallels that are already being drawn between Ebola and a “zombie virus”.

And because I like zombies B-)

See on Scoop.itVirology News

Packs of wild dogs spread Ebola after eating corpses!! Or…not, maybe?

13 October, 2014

Packs of wild dogs spread Ebola after eating corpses

The ever-evolving Ebola narrative is broaching into ludicrous territory, with reports now claiming that wild dogs are going around digging up the rotting remains of deceased victims and eating their flesh in the streets. Special Ebola graveyards, where the dead are being buried in haste and at shallow depths, are reportedly feasting grounds for these dogs, which officials say are capable of spreading the disease to humans.

The Daily Mail says Liberian villagers first came across the dogs while going about their daily routines. Right in the middle of busy streets, they said, hungry hounds were allegedly seen ripping through rotting corpses, to the shock of onlookers. After determining the source of the bodies, it was revealed that shallow graves were to blame.

Source: www.naturalnews.com

Stephen Korsman of the Division of Medical Virology at UCT just alerted me to this article, in some distress because they had misquoted him and used his comments out of context.  This is a rather wild, sensationalist and highly inaccurate piece from a fringe web site that seems to have blocked me from commenting, because of previous criticism.  So, I’ll just do it here.

They comment: "Logically speaking, it makes little sense that asymptomatic dogs are possible Ebola carriers while asymptomatic humans are not. There exists no credible science to substantiate this apparent inconsistency beyond the baseless claims made by government health officials."

Utter garbage: bats carry Nipah virus, SARS-CoV, Ebola, Marburg AND rabies essentially asymptomatically – and can transmit ALL of them to other mammals. So too can deer mice transmit Sin Nombre hantavirus in the south-western USA without showing symptoms.  Rodents transmit Lassa fever virus in West Africa every year, again without being symptomatic.  Mice can transmit various South American haemorrhagic fever viruses without obviously being sick. I wish they would get their facts straight: this is is very easily checked!

See on Scoop.itVirology News


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