Posts Tagged ‘eradication’

Should remaining stockpiles of smallpox virus be destroyed?

19 April, 2011

Our Department has a journal club every Friday, when research folk (staff and students) get together to hear a postgrad student present an interesting new paper.  Last Friday Alta Hattingh from my lab gave a thought-provoking and insightful presentation on whether or not smallpox virus should be destroyed – so I asked her to turn it into a blog post.

Should remaining stockpiles of smallpox virus (Variola) be destroyed? 

Raymond S. Weinstein

Emerging Infectious Diseases (2011), Vol 17(4): 681 – 683

Smallpox virus replication cycle.  Russell Kightley Media

Smallpox virus replication cycle. Russell Kightley Media

Smallpox is believed to have emerged in the Middle East approximately 6000 to 10 000 years ago and is one of the greatest killers in all of human history, causing the death of up to 500 million people in the 20th century alone.  Smallpox is the first virus to ever be studied in detail and it is also the first virus for which a vaccine was developed.  Smallpox was beaten by the Jenner vaccine (first proposed in 1796) and the disease was declared eradicated in 1980 in one of the greatest public health achievements in human history.

The last officially acknowledged stocks of variola are held by the United States at the Centres for Disease Control and Prevention (consisting of 450 isolates) and in Russia at the State Research Centre of Virology and Biotechnology (various sources place the number of specimens at ~150 samples, consisting of 120 strains).  This includes strains that were collected during the Cold War as potential for biological weapons due to their increased virulence. Then, there is also the added possibility that stolen smallpox cultures are in the hands of terrorists organizations.

In 2011 the World Health Organisation (WHO) plans to announce its recommendation for the destruction of all known remaining stockpiles of smallpox virus.  They have wanted to destroy the virus ever since 1980 when the Secretary of Health and Human Services, Louis Sullivan, promised destruction of US stockpiles within 3 years. This never happened in the US or Russia and no official recommendation for destruction have been recommended by the World Health Assembly.  In 2007 the final deadline for a decision was postponed until 2011 as no consensus could be reached among the executive board of the WHO.

The only real benefit that could be gained from destroying all known remaining stockpiles of smallpox virus in the world would be the prevention of causing a lethal epidemic due to theft or accidental release of the virus.  However, according to Weinstein destruction would only provide an illusion of safety and that the drawbacks of eliminating variola from existence are many.

In this paper Weinstein mentions the possible reasons behind the hesitance to destroy smallpox.  The prolonged existence of smallpox along with the important clinical implications of its high infectivity and mortality rates suggests that the human immune system evolved under the disease’s evolutionary influence.  In the last decade research has been done which suggests that variola (and vaccinia) have the ability to alter the host immune response by targeting various components of the immune system.  We are only beginning to understand the complex pathophysiology and virulence mechanisms of the smallpox virus.  An example of the importance of smallpox in human evolution is the CC-chemokine receptor null mutation (CCR5Δ32), which first appeared in Europe ~3500 years ago one person and today it can be found in ~10% of all those from northern European decent.  The mutation prevents expression of the CCR5 receptor on the surface of many immune cells and provides resistance to smallpox.  This same mutation also confers nearly complete immunity to HIV. In a recent study done by Weinstein and co-workers (2010) it was postulated that exposure to vaccinia and variola may have previously inhibited successful spread of HIV, suggesting that we swopped out one major disease for another. By eliminating the variola stockpiles from existence on-going research in this direction might be hampered and the possibility future studies employing intact virus will be rendered impossible.

Finally, we are capable of creating a highly virulent smallpox-like virus from scratch or a closely related poxvirus through genetic manipulation.  This renders moot any argument for the destruction of remaining stockpiles of smallpox in the belief that it would be for the benefit of protecting mankind.

In an editorial of the Vaccine journal, the editors make a compelling case in favour for the destruction of remaining stockpiles of smallpox virus.    To follow is their take on the situation:

Why not destroy the remaining smallpox virus stocks?

Editorial (by J. Michael Lane and Gregory A. Poland)

Vaccine (2011), Vol 29:  2823 – 2824

The Advisory Committee on Variola Virus Research (created in 1998 as part of the WHO) concluded that live variola is no longer necessary except to continue attempts to create an animal model which might mimic human smallpox and assist in the licensure of new generation vaccines and antivirals.

The editors feel that scientific recommendation for keeping smallpox stocks need to be scrutinized and that a number of political and ethical issues need to be addressed.  Below are comments by editors on these issues:

Scientific issues:

The smallpox virus is no longer needed to elucidate its genome, 49 strains have been sequenced and published, the editors feel that there is no need to sequence additional strains.  The smallpox virus can be destroyed as it is possible to reconstruct it from published sequences or to insert the genes of interest into readily available strains of vaccinia or monkeypox.  Refinements regarding diagnostics can be made by using other orthopoxviruses or parts of the smallpox strains already sequenced; vaccines have been produced that are far less reactogenic than the first and second generation of vaccinia vaccines and they are very effective against other orthopoxviruses.  Finally, the development of an animal model is difficult to perfect as variola is host-specific, thus there are no guarantees that a model will be found that mimics the pathophysiology of smallpox in humans.

Political/ethical issues:

The US is a supporter of the WHO and the UN and failure to comply with the request of the World Health Assembly jeopardizes the US’s potential to work with the UN to further their foreign policy and population health goals.  Biological weapons have been banned from the US military arsenal and there is no way they would use a biological weapons such as smallpox whether it be in offense or defence.  The editors reckon that the risk of a biological warfare attack using smallpox is highly unlikely as terrorists who have the knowledge and sophistication to grow and prepare smallpox for dispersal would realize that they could cause harm to their own countries.  Apart from that, Western nations have the facilities to isolate and vaccinate against smallpox in a timely manner.

According to the editors there is no ethical way to justify maintaining an eradicated virus.  Even though the possibility of accidental release is very small, it is an unacceptable risk.  Maintenance of the smallpox virus stocks is expensive and time consuming, it also burdens the CDC without scientific merit and their resources are better used to protect the public from infectious diseases.

In conclusion the editors maintain that the remaining smallpox stocks should be destroyed and the world should make possession of the virus an “international crime against humanity”.

We are presented with two very different views with regards to whether or not smallpox virus stocks should be destroyed forever.  The WHO meets again this year to decide the final fate of smallpox. Will the board reach consensus or will the smallpox virus yet again receive a stay of execution? 

Note added 1 Oct 2015

Interestingly, I found the following text written by me in my archive of articles – published as a Letter in the now sadly defunct HMS Beagle, in 1999:

HMS Beagle

( Updated May 28, 1999 · Issue 55)

Use logic, not fear

The destruction of all (known) stocks of smallpox virus (Reprieve for a Killer: Saving Smallpox by Joel Shurkin) seems to be a very emotive issue. Perhaps, if people looked at it less in terms of a threat, and more in terms of a resource, most of the problem would go away. For example, although the original article made mention of monkey pox, and how it was almost as dangerous as smallpox, and appeared to be adapting to human-to-human spread, nothing has been said about investigating why smallpox was so much more effective at spreading within human populations than monkey pox is. It is all very well having the smallpox genome sequence; however, without the actual DNA, it is difficult to recreate genome fragments of the size that may be needed to make recombinant viruses to investigate the phenomenon of host/transmission adaptation. Additionally, without the actual virus, it will be impossible to compare the effects of a doctored vaccine strain with the real thing. Destroying known stocks of the virus will not affect the stocks that are most likely to be used for bioterrorism. It will, however, handicap research into ways of combating the virus/understanding how it worked in the first place.

Rinderpest: gone, but not forgotten – yet.

5 November, 2010

Rinderpest virus infects cattle, buffalo and several species of antelope among other animals: it is a member of the genus Morbillivirus,family Paramyxoviridae, and is related to measles and mumps viruses in humans, distemper virus in dogs, and a variety of relatively newly-described viruses in marine mammals.  It also almost certainly gave rise to measles virus sometime around the 11th-12th centuries CE, as an originally zoonotic infection – sourced in domestic animals – took root in humans and began to be passed around (see MicrobiologyBytes).

Electron micrograph of a morbillivirus particle showing the membrane, matrix, and inner helical nucleocapsid. Image by LM Stannard

The ICTVdB generic description of morbilliviruses is as follows:

Virions consist of an envelope and a nucleocapsid. Virus capsid is enveloped. Virions are spherical to pleomorphic; filamentous and other forms are common. Virions measure (60-)150-250(-300) nm in diameter; 1000-10000 nm in length. Surface projections are distinctive spikes of haemagglutinin (H) and fusion (F) glycoproteins covering evenly the surface. Surface projections are 9-15 nm long; spaced 7-10 nm apart. Capsid/nucleocapsid is elongated with helical symmetry. The nucleocapsid is filamentous with a length of 600-800(-1000) nm and a width of 18 nm. Pitch of helix is 5.5 nm.

The Mr of the genome constitutes 0.5% of the virion by weight. The genome is not segmented and contains a single molecule of linear negative-sense, single-stranded RNA. Virions may also contain occasionally a positive sense single-stranded copy of the genome (thus, partial self-annealing of extracted RNA may occur). The complete genome is 15200-15900 nucleotides long.

Wikipedia describes rinderpest virus as “…an infectious viral disease of cattle, domestic buffalo, and some species of wildlife. The disease was characterized by fever, oral erosions, diarrhea, lymphoid necrosis, and high mortality.”   And: “The term Rinderpest is taken from German, and means cattle-plague.”

The Food and Agriculture Organisation (FAO) has a Division of Animal Production and Health: their web site details a campaign known as the Global Rinderpest Eradication Programme (GREP), which has been going since 1994.

With very little fanfare, I might point out: as a practicing teaching virologist, I was totally unaware of it.  Anyway: they state that:

Rinderpest has been a dreaded cattle disease for millennia, causing massive losses to livestock and wildlife on three continents. This deadly cattle plague triggered several famines and caused the loss of draught animal power in agricultural communities in the 18th, 19th and 20th centuries.

…which is a little of an understatement: Wikipedia tells us that

“Cattle plagues recurred throughout history, often accompanying wars and military campaigns. They hit Europe especially hard in the 18th century, with three long pandemics which, although varying in intensity and duration from region to region, took place in the periods of 1709–1720, 1742–1760, and 1768–1786. There was a major outbreak covering the whole of Britain in 1865/66.”

“Later in history, an outbreak in the 1890s killed 80 to 90 percent of all cattle in Southern Africa, as well as in the Horn of Africa [and resulted in the deaths of many thousands of people who depended on them]. Sir Arnold Theiler was instrumental in developing a vaccine that curbed the epidemic. [my insert / emphasis] More recently, a rinderpest outbreak that raged across much of Africa in 1982–1984 cost at least an estimated US$500 million in stock losses”.

When commenting on the significance of the achievement, John Anderson, the head of the FAO, described GREP’s announcement that Rinderpest had been eradicated as:

The biggest achievement of veterinary history“.

The 19th century southern African outbreak was devastating enough that people still remember it as a legendary time of hardship – and then there was the 1980s outbreak.  Another South African interest in rinderpest is that the legendary Sir Arnold Theiler had a hand in making a vaccine: he did this around the turn of the 20th century, by simultaneously injecting animals with blood from an infected animal and antiserum from a recovered animal: this protected animals for long enough to allow their immune systems to respond to the virus – but was rather risky, even though it was used for several decades.

In the 1920s J. T. Edwards in what is now the Indian Veterinary Research Institute serially passaged the virus in goats: after 600 passages it no longer caused disease, but elicited lifelong immunity. However, it could still cause disease in immunosuppressed cattle.

In 1962, Walter Plowright and R.D. Ferris used tissue culture to develop a live-attenuated vaccine grown in calf kidney cells.  Virus that had been passaged 90 times conferred immunity without disease even in immunosuppressed cattle, was stable, and did not spread between animals.  This vaccine was the one that allowed the prospect of eradicating the virus, and earned Plowright a World Food Prize in 1999.

But a memory may be all rinderpest is any more – as the GREP site says the following:

“The last known rinderpest outbreak in the world was reported in 2001 (Kenya). Based on the above-mentioned investigations, FAO is confident that all rinderpest virus lineages will prove to be extinct.”

This was also announced via the BBC on the 14th October, 2010.  They said:

The eradication of the virus has been described as the biggest achievement in veterinary history and one which will save the lives and livelihoods of millions of the poorest people in the world.

And the significant bit:

If confirmed, rinderpest would become only the second viral disease – after smallpox – to have been eliminated by humans.

Let us reiterate that: only the second viral disease, ever, to have been eliminated.  And how was this possible?  Unlike smallpox, which has only humans as a natural and reservoir host (although it almost certainly also got into us from animals), rinderpest attacked a wider range of hosts.  However, it seemed mainly to have a reservoir in domesticated cattle, and it did not have an arthropod vector; moreover, the vaccine was cheap and effective.

This is momentous news: we may well have succeeded in ridding the planet of what has been a very significant disease of livestock and of wild animals, which has caused untold agricultural loss throughout recorded history, and which has resulted in enormous human hardship as well.  We have also made a natural species go extinct – but it won’t be missed.  Like smallpox, it was completely sequenced some time ago, so we could theoretically recreate it if we ever needed to.

From GREP:

Though the effort to eradicate rinderpest has encountered many obstacles over the past several decades, the disease remains undetected in the field since 2001. As of mid 2010, FAO is confident that the rinderpest virus has been eliminated from Europe, Asia, Middle East, Arabian Peninsula, and Africa. This has been a remarkable achievement for veterinary science, evidence of the commitment of numerous countries, and a victory for the international community.

Amen.  However – it’s not quite time to celebrate as the certification is only planned for 2011.

And now for mumps, and measles too.