Posts Tagged ‘Rift Valley fever’

Monkeypox vaccine?? We don’t need no monkeypox vaccine….

22 December, 2011

An in-press article in Vaccine that was tweeted by MicrobeTweets (well worth signing up to, BTW) has the intriguing title “Whither monkeypox vaccination?”

Now, some background to this: monkeypox virus is a rather nasty relative of smallpox (family Poxviridae; subfamily Chordopoxvirinae, genus Orthopoxvirus), meaning it is a large dsDNA virus (170-250 kb) with a complex structure.  The virus is endemic in remote forest areas in central Africa – principally in the Democratic Republic of the Congo – and naturally infects a number of animal species, including giant pouched rats (Cricetomys sp.), dormice (Graphiurus sp.) and African squirrels (Heliosciurus, Funisciurus), as well as laboratory monkeys, which is how it was isolated and got its name.

Monkeypox gets transmitted to humans by contact with infected animals: this includes by simple handling, as well as by exposure to meat and blood of butchered animals.  It causes a disease in humans that is very similar in appearance to smallpox, with a case fatality rate of 1-10%, but is apparently far less easily transmitted person-to-person.  It caused only sporadic and limited outbreaks in Africa and was of limited interest until an outbreak in the USA in 2003, which was linked to young prairie dogs kept in a pet store in close proximity to an infected Gambian pouched rat (Cricetomys gambianus) recently imported from West Africa. Seventy-three people were reportedly infected, among whom there were no fatalities.  The CDC recommends vaccination of people exposed to human or suspected animal cases with smallpox vaccine, as this protects animals from experimental lethal monkeypox challenge.

The Vaccine paper makes the point that the potential for monkeypox virus (MPX) to fill the disease niche recently vacated by smallpox was evaluated in the 1970s – and discounted, largely because human-to-human spread was inefficient enough for outbreaks not be self-sustaining – thus, although smallpox vaccine protected against MPX, the WHO thought there was insufficient justification to continue vaccination.

Now, however, the incidence of the virus in humans

“…appears to have markedly increased. In addition to diminished vaccine-induced orthopoxvirus immunity, there have been profound social and demographic changes that have increased human MPX exposures and the likelihood of severe disease. Recurrent civil war and subsequent economic decline have forced rural residents to flee deep into the rain forests for extended periods of time, disrupted traditional village life and increased dependence on hunting for sustenance, thus increasing exposure to animal reservoirs of MPX.”

So, in other words, people are getting a whole lot more exposure to sick animals.  Increasingly, by eating them.  The paper goes on to say:

“Although orthopoxviruses are relatively genetically stable MPX has diverged into two clades with different levels of virulence. As incidence rises, each new MPX infection provides an opportunity for viral evolution or adaptation that may result in a more virulent or contagious variant capable of sustained person-to-person transmission. These new circumstances merit a re-evaluation of the need for immunizing against MPX”.

So – that should be relatively simple, surely?  I mean, South Africa alone has millions of doses of smallpox vaccine safely frozen away from the 1970s?  Not so fast….

“However, in an era where the threat of smallpox is not imminent and there are conditions such as AIDS, tissue transplantation, and therapies for cancer and autoimmunity that cause immunodeficiency, the adverse events associated with live vaccinia are no longer considered acceptable for the general population.”

The paper goes on to mention how all sorts of supposedly safe new smallpox vaccines have been deposited into biodefence stockpiles, based on animal testing.

And there it is again – that word “biodefence”, in the context of human vaccines – implying that there is a “biothreat” to counter.  Specifically, in this case, the spectre of weaponised smallpox.

The authors go on to make reasonable statements about surveilling for monkeypox in central Africa, and vaccinating people at risk, and say that treatment options should also be investigated given that clinical diagnosis is relatively easy.

They also close with this:

“If immunization studies in developing countries are contemplated to support the licensure of orthopoxvirus vaccines for industrialized countries or for military purposes, then provisions from those countries or organizations should be secured to distribute successful products in endemic regions where the products were tested.” [my emphases]

I should hope so.  I should really, really hope so – because then one country’s biodefence interests could end up benefitting quite a few others, who are the ones who really need the product.  Now, while you’re busy with that, what about vaccines for Rift Valley fever, Crimean-Congo haemorrhagic fever and Chikungunya – which are actually far more serious a problem, in a much bigger geographical area?


Rift valley fever: a problem – and a solution?

17 March, 2010

Rift valley fever virions: Linda Stannard, UCT

It was an interesting week, what with a Rift valley fever virus (RVFV) outbreak in South Africa associated with two human deaths – and an excellent journal club presentation (thanks, Liezl!) on a new candidate virus-like particle vaccine made in insect cells.  RFV was in fact worked on in the 1960s at UCT in the old Virus Research Unit under the legendary Dr Alfred Polson at the then Medical School (see pictures link here) – and a couple of folk even got infected while trying to purify it, but we won’t speak of that.

First, the news:

Health-e (Cape Town)

South Africa: Rift Valley Fever Update – a Total of 21 Cases Have Been Confirmed

15 March 2010  press release

The following is a statement by [South African] Deputy Minister of Health Dr Molefi Sefularo, MP, pertaining to the recent deaths from Rift Valley Fever in South Africa.

As of 15 March 2010, a total of 21 human laboratory confirmed cases of River [sic] Valley Fever (RVF) have been confirmed – all acquired in Free State – with two deaths. This brings a total to 22 human cases of RVF – with one in Northern Cape.

Most of these cases reported direct contact with RVF-infected livestock and or linked to farms with confirmed animal cases of RVF. The human cases are; farmers, veterinarians and farm workers. Additional suspect cases are currently being tested.

While there is no specific treatment, the majority of persons affected will recover completely. People should avoid contact with the tissues of infected animals, refrain from drinking unpasteurised milk and prevent mosquito bites to avoid becoming infected. Farmers and veterinarians should wear protective clothing when handling sick animals or their tissues. There is no routine vaccine available for humans.

Rift Valley Fever (RVF) is a viral disease that can cause severe disease in a low proportion of infected humans.

The virus is transmitted by mosquitoes and causes outbreaks of abortion and deaths of young livestock (sheep, goats and cattle). Humans become infected from contact with infected tissues of livestock and less frequently from mosquito bites. In sub-Saharan Africa the mosquitoes which transmit the virus do not enter human dwellings but feed on livestock outdoors at night. The disease occurs throughout Africa and Madagascar when exceptionally heavy rains favour the breeding of the mosquito vectors.

Clinical features in humans

Typically illness is asymptomatic or mild in the vast majority of infected persons, and severe disease would be expected to occur in less than 1% of infected persons.

Key symptoms:

The incubation period (interval from infection to onset of symptoms) for RVF varies from two to six days.

  • Sudden onset of flu-like fever and/or muscle pain.
  • Some patients develop neck stiffness, sensitivity to light, loss of appetite and vomiting.

Symptoms of RVF usually last from four to seven days, after which time the immune response becomes detectable with the appearance of antibodies and the virus gradually disappears from the blood.

Severe form of RVF in humans includes:

  • Vision disturbances
  • Intense headache, loss of memory, hallucinations, confusion, disorientation, vertigo, convulsions, lethargy and coma and;
  • Haemorrhagic Fever [rarely – Ed.]

The public living in the affected areas is encouraged to seek medical attention at their nearest Health facilities, should they have any of the above symptoms.

This is an unusual outbreak, because these normally occur only in high summer rainfall regions near the tropics, on the African east coast – and not far inland in essentially arid distinctly sub-tropical areas, like the Free State and Northern Cape.

However, there is news at hand that may be of use in the future: while there is currently no human vaccine, and veterinary vaccines are apparently so attenuated as to require several applications to be effective, SM de Boer and colleagues in The Netherlands claim that subunit VLP vaccines derived by envelope glycoprotein expression in insect cells appear to confer complete protection in vaccinated animals.

Vaccine. 2010 Mar 8;28(11):2330-9. Epub 2010 Jan 5.

Rift Valley fever virus subunit vaccines confer complete protection against a lethal virus challenge.

de Boer SM, Kortekaas J, Antonis AF, Kant J, van Oploo JL, Rottier PJ, Moormann RJ, Bosch BJ.

“Here we report the evaluation of two vaccine candidates based on the viral Gn and Gc envelope glycoproteins, both produced in a Drosophila insect cell expression system. Virus-like particles (VLPs) were generated by merely expressing the Gn and Gc glycoproteins. In addition, a soluble form of the Gn ectodomain was expressed and affinity-purified from the insect cell culture supernatant. Both vaccine candidates fully protected mice from a lethal challenge with RVFV. Importantly, absence of the nucleocapsid protein in either vaccine candidate facilitates the differentiation between infected and vaccinated animals using a commercial recombinant nucleocapsid protein-based indirect ELISA”.

Great accomplishments; great paper – and I note that if you can do it in insect cells, you can do it in plants…just like influenza viruses.

Because, as de Boer et al. state in their Introduction:

“Although the overall case-fatality rate is estimated at 0.5–1.0%, recent outbreaks show considerably higher numbers. The high case-fatality rates combined with the potential of rapid spread via its vector explains the recognition of RVFV as a potential bioterrorism agent by the United States government. Given the impact of RVF outbreaks on livestock, the human population, and the economy, there is an urgent need for a safe and effective vaccine.” [my emphases]

And one backed by the US Government – which used to work on it as a bioterror agent, according to Wikipedia.  Ah, well: some day they’ll just want to do it because it’s the humanitarian thing to do.  Like now, possibly: DARPA is funding Fraunhofer USA to the tune of $4.4 million to make H1N1 vaccines in plants, following their successes over the last couple of years in especially transiently expressing HA proteins.

Going green: the sensible thing to do.