Monday, February 08, 2016

Zika - what shall we do if the scientists are not sure what it does?

David L Heymann, the WHO Zika chief, has just announced that the causal connection between Zika virus and the cases of microcephaly in east Brazil is not 100% certain.

This means that medical scientists have to look carefully at the epidemiology of the cases, and search for neurological (especially foetal) damage in previous outbreaks. They will look at the genome of ZikaVirus (ZIKV) to see if it has mutated, and if so, where (geographically) it mutated, and why. The answer to the last question is most likely "It was a spontaneous mutation", but causes should nevertheless be looked for. There are about 20 main causal agents for microcephaly.

Cytomegalovirus and Rubella virus are known to be able to cause microcephaly, and so ZIKV would be the third virus on the list.

Establishing the causal link beyond reasonable doubt could take years, though we will probably have a firmer idea about the cause of the microcephaly in a few weeks. The thing is, there is loose, sloppy thought behind the question "Can you prove that ZIKV causes microcephaly?" Science, unlike mathematics, does not prove things.

Whatever the cause, it is clear that policy should be precautionary, but not hysterical (which mainly means not in a pesticide spraying way). Research on defence against ZIKV - vaccines, antivirals - must go on. Research on sterile male releases must continue, but with close monitoring  of where and for how long the GM mosquitoes survive.

But the key thing is that community-based Mosquito Habitat Source Reduction - clearing stagnant water etc- must go on.

It must go on for one very good reason: even if (against all expectations) it should turn out that ZIKV does not cause microcephaly, it is pretty clear that it causes Guillain-Barre syndrome. It is also true that mosquitoes carry malaria and about 15 other diseases that cause illness, death, poverty, inequality and generally hold humanity back. On the other hand, a victory over the mosquito would be a huge boost to community morale.

David Heymann said another interesting thing. We do not know for certain that ZIKV could not gain a foothold in a British based mozzies. This means that we in the UK need to keep calm and keep a firm grip on possible mosquito habitats.

Sunday, January 31, 2016

Economic opportunities in responding to the Zika Virus threat

The WHO is deeply concerned about the rapidly evolving Zika Virus (ZIKV) situation for 4 main reasons:
  • the possible association of infection with birth malformations and neurological syndromes
  • the potential for further international spread given the wide geographical distribution of the mosquito vector
  • the lack of population immunity in newly affected areas
  • and the absence of vaccines, specific treatments, and rapid diagnostic tests

The situation is urgent not just because of the immediate medical threat, but also a threat to the economy of Brazil. If fear of ZIKV deters people from attending the Olympics, scheduled for August 2016, this could negatively impact the economy of Brazil, which is already in a downturn. If Brazil goes into full recession as a result of a disappointing Olympics, this would be a factor pushing the global economy into recession.

For these reasons it it vital that the threat from ZIKV be neutralised.

There are two main lines of defence:

Measures against the virus
There are no antivirals available against the ZIKV at present.
A vaccine may take about a year to come on line - though Indian researchers are claiming they have a vaccine already (Feb1).
Medical research and technology will go ahead, and will no doubt be productive, but not in a time frame that can affect the situation in August 2016.

Measures against the vector
There are a range of measures that we can take against the mosquito that carries the virus, Aedes Aegyptii.

At the high tech end, the UK firm Oxitec have been releasing millions of Aedes male mosquitoes which are genetically modified so that 97% of their progeny do not reach adulthood. This technique has produced promising results in the Cayman Islands, Malaysia and Brazil, with reductions in mosquito numbers of around 90% reported.

However, it was found that in the presence of tetracyclines, (which are plentifully available in agricultural effluent) up to 15% of the progeny may reach adulthood. The effects of this have been studied, and the conclusion is that the levels of tetracycline in the environment where Aedes Aegyptiae likes to lay its eggs are not high enough to affect the Oxitec process.

There are fears that the operative bit of the genetic engineering, the transposon element, may affect the virus itself. However, the transposon is designed to work on DNA, and will not affect the virus, which works on RNA. 

Also there are suggestions in social media that since the microcephaly problem emerged in the same place as an Oxitec roll out of GM mosquitoes, the GM may in some way have caused the microcephaly. In fact the epicentre of the outbreak is many kilometers from the place where GM mosquitoes were released .

Although the fear that the GM caused the outbreak are without evidential foundation, it may well have an effect on the popular view of the GM solution, and cooperation with the authorities.

Whether or not GM methods are used to control mosquito populations, there is still a need for more conventional defences.

Pesticides do have a place in the system of defence. The best application is in pesticide-impregnated mosquito nets. These are very precise; they kill female mosquitoes that are seeking blood, attracted by the CO2 and odours emitted by humans. Next comes indoor spraying, onto walls and in closets and dark spaces, which are preferred nurseries for Aedes Aegyptiae.

At the other end of the scale of acceptability is general outside fumigation with pesticide. This may have a place in extreme scenarios, but the approach is inefficient and harmful to the health of humans and beneficial insects. Pesticides have a limited working life as resistance is inevitable, and the more they are used, the quicker resistance will develop. [updated]

Mosquito Habitat Source Reduction (SR) is the classical and proven defence against mosquitoes. It means removing their habitat – stagnant water – as far as is reasonably practical. This means emptying any potential of water – litter, tyres, containers gutters, puddles, hollow trees and especially open sewers.

The task is simple. Accomplishing the task, and making a permanent habit of it is extremely challenging, but not impossible.

A successful source reduction programme would look something like this:

Each neighbourhood would have one or more Source Reduction Officer (SRO) appointed.
This would be a paid post.
The officers would be chosen from the neighbourhood.
They would be trained to know why SR is so important, and able to pass on their knowledge to their neighbours.
People would be expected to cleanse their own properties voluntarily, but work carried out in common areas should be paid for.
Anyone in receipt of state benefits would be paid for their work in addition to their benefits. Neighbourhoods would be inspected periodically from outside, incentivised by rewards and compliments for success, and in the event of failure, the SRO may be replaced.

Favellas and other poor communities would need additional help in setting up their programme.

The programme of sewer modernisation would provide a significant economic stimulus, which is particularly welcome in a recession.

Politicians and economists must see the SR programme as the excellent investment that it is.
Lack of money must not be offered as an excuse for inaction.

In addition to SR, the Government will make sure that every citizen has access to pesticide impregnated mosquito nets, screens and any other relevant materials and knowledge.

The rewards of success of this programme are as follows

  1. Comfort and amenity for all
  2. Costs of disease avoided
  3. Costs of disability (microcephaly) avoided
  4. Demand reduction on local health services
  5. Employers would find that sick leave is less.
  6. Work opportunities for Brazil's 7% unemployed, with reduction in income inequality in the country.
  7. Improved visual amenity as litter disappears, which would boost tourism.
  8. General morale will benefit as people get the satisfaction of realising that they themselves have helped to defeat the mosquito and the disease it causes.
  9. This sense of empowerment may encourage formation of similar programmes.
  10. Roll-out of successful programmes can provide an effective model for other mosquito-affected countries.

Conclusion
The challenge of ZV gives us an opportunity of transforming community life economically and in other ways by engaging ordinary people in the fight against disease.

31/1/2016
Dr Richard Lawson MB BS, MRCPsych


Could GM mosquitoes be responsible for Zika microcephaly?

Since my post about ZikaVirus (ZV) here yesterday yesterday, I have been discussing the matter intensively.

Two things have emerged. 

One is that the idea of actually eliminating disease-carrying mosquitoes is highly contentious, so much so that it is not a good idea to discuss at this stage. Better to think in terms of reducing mosquito populations and opportunity for them to contact humans.
.
Second is that there is a suspicion that the cases of microcephaly were first recognised in the same part of Brazil that the Oxitec genetically modified mosquito (GMM) was released in 2012. IN fact the GM release was 300km away from the place Zika appeared, and separated by 2 years. 

People are concluding that somehow the GMM contributed to the microcephaly cases. The idea is running on social media, and RT has carried it. FoE USA have also expressed concern that in the presence of tetracycline antibiotic, the GMM progeny will have a survival rate of 15%. The Ecologist carries a write-up of the GM theory.

So could the GM technique somehow be responsible for a change in the virus that causes it to cause microcephaly? This is unlikely, but the question deserves an answer.

It is possible that ZV has  always caused microcephaly, but the association has not been noticed until now.

It is impossible that the Oxitec process could affect the virus gene, since the GM process is aimed at DNA, whereas the virus is an RNA organism.

ZV was first found in a monkey in Uganda in 1947, and was unremarkable until 2007 when it spread to the Pacific islands. Air travel facilitated this jump, and global warming is in the process of extending the mosquito's range.

The WHO Director General reports that neurological disorders were noticed after an outbreak in French Polynesia in 2013. The WHO D-G also adds "Arrival of the virus in some places has been associated with a steep increase in the birth of babies with abnormally small heads and in cases of Guillain-Barre syndrome".  French Polynesia had an outbreak of ZV in 2014-15. Health authorities found 17 central nervous system malformations, and four of these tested positive for ZV. Oxitec was not deployed in Polynesia. This is sound evidence that ZV does microcephaly on its own, without help from GM.


To get a definitive understanding, researchers need to look methodically at the incidence of microcephaly in other areas that have suffered Zika virus outbreaks. Research can also compare the incidence of microcephaly (and maybe Guillain Barre) rates in the Cayman Islands and other areas of Brazil where your GMM have been introduced, and compare the figures with outbreaks where there are no GMM.

These studies are likely to take at least a year.

In the meantime the basic position is that we need to defend ourselves against Zika virus by taking action at every level of technology, including antivirals, vaccines, and measures against the vector, including targeted pesticides and the Oxitech technique if it can be cleared of harmful effects, but above all we must prioritise action by local communities in eliminating unnecessary standing water.

The slight cloud over GMM just emphasises the need for a full-on programme of source reduction - reducing any stagnant water. This deserves a post of its own (here).

This post has been updated 1/2/16 & 2/2/16, 5/2/16
More on this from Mark Lynas in the Guardian

Friday, January 29, 2016

Zika crisis - danger and opportunity

Aedes Aegyptiae mosquito


Zika virus is causing a lot of justifiable concern right now. It is reasonable to call it a crisis.

Crisis means danger and opportunity.

The danger is that it can cause a huge number of people with microcephaly mainly in tropical regions, but it also presenjts us with the opportunity to eradicate the mosquito that carries it.

The virus was first identified in 1947, as the cause of a mild flu-like illness, often with a rash, but it has recently been associated with a birth defect - microcephaly, or small brain - in women who get Zika in the first 3 months of pregnancy. It is also linked with a high number of cases of Guillian-Barre syndrome, where weeks of near-paralysis follow a virus infection.

Initially the virus was limited to tropical Africa, but has recently spread rapidly to many countries that host the Aedes aegyptii  mosquito. Note that this is different species from the Anopheles that carries malaria.

Two factors lie behind this explosion of Zika - air travel, and climate change. The warming global climate will inevitably increase the mosquito habitat. It is possible that the virus has mutated.

This map shows the countries which are vulnerable to Aedes mosquito, and therefore to Zika virus.


Note that Florida and the South Eastern USA are potentially affected. This changes everything. The disease is not there yet, but it is only a matter of time, and when it arrives it will motivate the US Government to do something to neutralise the mosquito threat.

Note also that it threatens the success of the Brazil Olympics. Any woman (and her partner) who is pregnant, or contemplating pregnancy, should stay away as things stand now.

These factors will push for a quick solution to the problem.

There are two approaches on offer: attack the virus, or attack the mosquito that spreads it.

Attack the virus? A vaccine will take a year or so to develop, and there are no antiviral treatments (except one success with the impossibly expensive interferon).

So we are left with the anti-mosquito approach, which is much more promising and interesting.

We know a lot about mosquito control, because they carry no less than 16 diseases: not just malaria (which causes 200 million cases a year and 440,000 deaths) but also 


  • dengue fever
  • yellow fever
  • West Nile virus
  • Saint Louis encephalitis virus
  • Eastern equine encephalomyelitis virus
  • Everglades virus
  • Highlands J virus
  • La Crosse Encephalitis 
  • Ilheus virus
  • filariasis (elephantiasis)
  • Rift Valley fever
  • Wuchereria bancroft
  • Japanese Encephalitis
  • chikungunya
  • Murray Valley encephalitis

    That it one hell of a lot of illness, suffering, grief, burden on health services and economic loss.


  • Why do we put up with it?

    Maybe because up to now the mosquito has been a pest that affects poor tropical countries. 

    Rich visitors can cope by taking measures (see below), so it tends to get ignored.

    We now have an opportunity to mobilise public opinion, motivate politicians and control, or even eradicate, the mosquito.


    Mosquito Control
    Control starts with the personal.
    In areas with mosquito-borne disease, 
    • take anti-malarials (I personally know of the case of a young couple who died of malaria because they refused to take "Western Medicines")
    • use mosquito nets soaked in insecticide
    • apply insect repellent if outside of the net, especially at dawn and dusk (though the Zika virus can be transmitted during the day too).
    • keep the house clear of mosquitoes with screens and insecticide .

    Outside fumigation with insecticide is dubious, because it kills beneficial insects and raises the chance of resistance developing.

    Mosquito traps  may have a role.

    The main attack outside the house is more interesting: denial of habitat. 
    This is great, because it is low-tech, creates work, and is aesthetically pleasing.

    The aim is to eradicate any pools of standing water. This means
    • modernising open sewers
    • draining or filling puddles
    • tidying up litter (water can pool in any concave surface in discarded plastic, tyres etc)
    • clearing and filling nooks and crannies
    • more here
    This means that Rio and other Olympic cities should be clean and tidy, sparkling for its visitors in August, and the population will be pleased because they will all have been in work and therefore less poor. The abolition of open sewers would be a huge step forward from every point of view - aesthetic, medical, economic, political.

    Marshes and other watery areas can be managed. Bio-control involves introducing fish or other things that eat mosquito larvae, but this can be ecologically disruptive.

    All of this denial of habitat will create a huge number of jobs, so is a boon to the poor and the unemployed. Because there is such a good return on investment, funding should not be a cause of delay.

    There is even a case to be made for governments to create the money needed to pay for the work directly. Money is created mainly by banks through debt, but governments give them the power to do this, and therefore governments also have the power to create money directly, and this is a very reasonable thing to do if it brings future savings of expenditure, and is good for the health of the people, which is after all, the purpose of government.

    Last but not least, we have a promising new treatment - release of sterile male mosquitoes.

    Oxitec is an Oxford based company which is producing millions of genetically modified male mosquitoes. These can mate with female mosquitoes, producing young which die before they can reproduce. The product has been approved and trialled and is already in use in Brazil.

    Some may be surprised that a Green blogger and activist is backing this GM technique. The point here is that the technique is for the good of humanity, that the GMOs we are talking about here are intrinsically not self replicating beyond their own immediate progeny. Greens are not against genetic modification per se, but because of  specific problems arising from some applications. 

    The GM approach, combined with the other measures mentioned above, should be able to reduce or even eliminate the threat by the time of the Olympics if everyone concerned including the politicians does their work efficiently.

    Assuming we win a famous victory over the virus for the Olympics, we will have a model that can be rolled out in the rest of the world. If pursued to the end, we could eliminate the mosquito from the face of the planet.


    Would it matter if the mosquito were driven to extinction? They do provide food for birds, insects and bats, but they are not wholly reliant on them, and even the mosquito fish can live on other larvae.

    It is possible if not probable that another insect will move into the niche, but we can inspect that situation when it arises. It is unlikely that it will be worse than the mosquito.

    Here is an article in Nature about the effects of mosquito extinction. It suggests the worst outcome would be - an increase in the human population.

    There may be unknown effects from mosquito eradication, but it would be unreasonable to oppose eradication of a known major problem on grounds of some future unspecified possibility.


    Over the next few months, we need to have a big debate about whether we want to make some or all species of mosquito extinct. The question has been raised by Dr Olivia Judson here.

    So, in summary:
    • Zika is a major problem
    • It can be contained by attacking the mosquito population
    • A combination of low tech job-creation and high tech GM techniques can beat the problem, given the political will

    Monday, December 07, 2015

    How do the Cumbria floods relate to global warming?



    The floods in Cumbria are due to an abnormally heavy rainfall event. The Met Office says that a new record had been set for rainfall over a 48-hour period, with 15.9in (405mm) falling in 38 hours at Thirlmere in Cumbria.

    The Met says "just as with the stormy winter of two years ago, all the evidence from fundamental physics, and our understanding of our weather systems, suggests there may be a link between climate change and record-breaking winter rainfall. Last month, we published a paper showing that for the same weather pattern, an extended period of extreme UK winter rainfall is now seven times more likely than in a world without human emissions of greenhouse gases.”

    The flooding is consistent with global warming theory, since warmer air can carry, and therefore deposit, more water.

    An air mass coming up from the Gulf of Mexico passed over unusually warm Atlantic waters, which gave it added moisture.

    The current El Nino is not directly operative, since it should mean colder drier winters in Northern Europe, and warmer, wetter winters in Southern Europe.

    Ocean cycles supply the immediate cause of the flooding, but global warming means that the cycles will inevitably become warmer as years go on, since 90% of the heat received by the Earth goes into the oceans.

    As ever, we do not say any one event is caused by global warming, but we can say that the warming increases the frequency and intensity of floods, heat-waves and other extreme events.

    Nothing is ever "proven" in science, but it sure can disprove theories.

    And the lukewarmer/denialist theory that man-made climate change will not have a serious impact on world weather patterns is most certainly disproved and refuted by all the evidence. So far, our changes have increased the global temperature by 0.9*C. The "lukewarmers", who have an undue influence on George Osborne, claim that a 2*C elevation would have only a mild effect on global weather. They are utterly and dangerously wrong. Warmer air means more flooding. Period.