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Latest updates on Zika – Expert reaction

Posted in Science Alert: Experts Respond on February 5th, 2016.

As more Zika virus cases are reported in South America and the Pacific, media attention has turned to GM mosquitoes and the first  infection – a pregnant woman – reported in Europe.

Aedes_aegyptiIn Spain, health authorities have confirmed a pregnant woman recently returned from Columbia is infected with the virus. It is the first reported case in Europe and officials are confident the virus is unlikely to spread. Expert commentary from the UK SMC is available below

A number of outlets have also reported on a potential link between Zika virus infections and the release of Oxitec genetically modified mosquitoes in Brazil. The mosquitoes, modified to slow the spread of existing mosquitoes using the sterile insect technique, were released in 2015 in the same area as a clustering of Zika cases. Read expert comments below.

Meanwhile, the Genetic Expert News Service (GENeS) in the US has collected expert commentary examining the potential effectiveness of Oxitec mosquitoes in limiting natural population numbers. Read the commentary below.

Commentary from the UK SMC on the case of pregnant woman infected with Zika in Spain.

Dr Derek Gatherer, Lecturer in the Division of Biomedical and Life Sciences, Lancaster University, said:

“Spain has become the latest country to have Zika imported via travellers returning from Latin America. We have already had a handful in the UK, and the USA has had upwards of two dozen.  These cases do not pose any risk to the general population of Spain or any other European or North American country, since although one potential vector, Aedes albopictus, does exist in some Mediterranean coastal regions of Spain, we have no reason to believe that any outbreak could be sustained in human populations in Spain given the general level of infrastructural development of that country.  For similar reasons, chikungunya failed to establish itself in Italy after the 2007 outbreak, and both dengue and chikungunya have only caused very sporadic problems in the South-eastern USA.

“The question as to the wellbeing of the pregnancy in one infected female cannot be answered without further information.  Since her pregnancy may have been in relatively early stages when she was infected, there may be a risk.  We have no statistics as yet on the frequency of microcephaly in infected pregnant women, nor any hard data on the riskiest parts of pregnancy.  The matter is now in the hands of the obstetrician caring for the pregnant woman.  Ultrasound imaging will be a priority.”

Dr Ed Wright, Senior Lecturer in Medical Microbiology, University of Westminster, said:

“The importation of further cases of Zika virus into Europe is of no surprise, however, what stands out in this situation is that one of the individuals is pregnant.  With a possible link between Zika virus infection and microcephaly, concern has been raised regarding the health of the baby.  At the moment there is not enough evidence to give a definitive answer to this question due to insufficient or conflicting data. For example, Brazil has seen an increase in microcephaly cases that coincides with the outbreak of Zika virus, while no cases of microcephaly have been linked to Zika virus infections seen in neighbouring Columbia.  Whether that link stands up to scientific scrutiny is something scientists and healthcare professionals are urgently trying to determine.  Collection of accurate, reliable epidemiological and clinical data over the coming weeks and months will hopefully provide the answers we need so at risks groups can be given appropriate advice and support.”

Dr James Logan, Senior Lecturer and Director of arctic, Department of Disease Control, London School of Hygiene & Tropical Medicine, said:

“These imported cases are not surprising and we are likely to see more in other countries in the weeks to come. It is important to note, however, that Zika was picked up abroad and not in Spain. Pregnant women in particular should be aware of the risks when they travel to high risk countries and if they do choose to travel they should take appropriate precautions which include using an insect repellent containing DEET at a concentration between 20-50%. They should also cover up with long sleeved clothing and can wear permethrin impregnated clothing.

“Importantly they should be aware that mosquitoes that transmit the disease bite readily during day. Bed nets, which only work at night, should still be recommended due to the risk of other insect borne diseases.”

Prof Jonathan Ball, Professor of Molecular Virology, University of Nottingham, said:

“It’s a really unfortunate development but it was almost inevitable that a pregnant woman would become infected visiting the worst hit areas. That is why very recent advice is for pregnant women to avoid travel to those countries.

“Even though there is a reported link between Zika infection during pregnancy and a risk of a baby being born with microcephaly, we can’t yet be absolutely sure.

“If this link is proven beyond reasonable doubt we still don’t know what the chances are of a baby developing this condition, nor if there are particular times during the pregnancy when the baby is at most risk.

“It does provide a salutary reminder, if one were needed, that there is so much that we do not know about this virus even though we’ve been aware of it for many decades.”

A number of outlets have reported on a potential link between Zika virus infections and the release of Oxitec genetically modified mosquitoes in Brazil. The mosquitoes, modified to slow the spread of existing mosquitoes using the sterile insect technique, were released in 2015 in the same area as a clustering of Zika cases.

The UK SMC collected the following expert commentary.

Prof John Edmunds, Dean of Faculty of Epidemiology & Population Health, and Professor in the Centre for the Mathematical Modelling of Infectious Diseases, London School of Hygiene & Tropical Medicine, said:

“Infectious and vector-borne diseases always cluster in this way by their very nature – i.e. one person infects another, in this case usually via mosquito bite.  So if Zika does lead to microcephaly then it would be very surprising if microcephaly were not found in clusters like this.”

Prof Jonathan Ball, Professor of Molecular Virology at the University of Nottingham, said:

“There could be several reasons for clusters of microcephaly. It could be down to increased monitoring and diagnosis in those areas or these could be hotspots for Zika virus infection simply caused by differences in mosquito numbers.  At the moment we don’t know how the virus is spreading, whether there are waves of infection moving across the Americas, or are their random introductions from one part of the region to another, which then take hold and spread locally.

“It is precisely because of this lack of knowledge about what’s happening on the ground that WHO have ramped up effort and why we as a research community need to start to work together to work out how the virus is spreading and behaving.

“I would say however, that it is absolutely inconceivable to think that any clusters of infection or potential microcephaly cases are down to the introduction of genetically modified mosquitoes.  The modified mosquitoes that are released are male and we know that Zika virus is spread by the females when they take a blood meal – these have not been modified.  The poison gene that the mosquitoes are programmed with can be passed onto female offspring, but these will die before they ever become a mature, flying and biting insect.”

Prof Michael Bonsall, Professor of Mathematical Biology at the University of Oxford, said:

“It is unlikely that this disease cluster is caused by the release of GM mosquitoes.  For this cluster to emerge there must be an increased incidence of mosquito (principally Aedes aegypti) carrying Zika and biting people.  The GM insect trials underway in Brazil are self-limiting male mosquitoes – these mosquitoes pass a lethality gene onto their offspring and these mosquitoes die before they reach the adult stage, the aim being to make the mosquito population smaller.  Also – and importantly – male mosquitoes don’t bite.

“Understanding the factors that generate these sorts of clusters need more scrutiny but they are an expected statistical occurrence – perhaps due to seasonal fluctuations in female mosquitoes numbers and coincidence Zika prevalence – but the key issue is understanding all the facts that lead to these sorts of outbreaks.”

Dr Clare Taylor, Senior Lecturer in Medical Microbiology and General Secretary for the Society for Applied Microbiology, said:

“Brazil appears to be the only country currently where Zika is associated with microcephaly.  For example, in Colombia there are some 20,000 confirmed cases of Zika (~2,100 are pregnant) but no reports of microcephaly.  It is possible that cases are not reported or undetected.  However, there were cases of Zika in French Polynesia in 2013 & 14 and an increase in autoimmune and neurological diseases has been observed (73 cases, 42  Guillain-Barré Syndrome).

“There are numerous websites speculating that there is a connection between the recent release of GM mosquitoes in Brazil and the microcephaly cluster sites.  However, there is no evidence that the release of GM mosquitoes is associated with either Zika or microcephaly.  In contrast, a report from 2015 suggests that the genetic lineage of the Zika isolated in Brazil is closely related to that from French Polynesia (99% similarity).  The report speculates as to potential routes of transmission of Zika from French Polynesia to Brazil.”

Prof Paul Reiter, recently retired consultant on mosquitoes and mosquito-borne diseases and Professor of Medical Entomology, Pasteur Institute, responds:

“The claim that Oxitec is in any way to blame for the tragic outbreak of Zika is outrageous.  For more than half a century we have fought the rising surge of dengue and chikungunya in vain (they are transmitted by the same urban mosquito).  At last we have a novel and highly promising approach yet some purveyors of myth-information are trying to scupper it”.

“The accusers are misusing the language of science to serve their own agenda. To me they are on a par with the eugenicists who claimed that Chinese and Jews (as opposed to elephants?) are of inferior intelligence to Europeans because they have smaller brains; the immigration quotas of many countries were tailored to such non-science.  Perhaps a better example was the success of Trophim Lysenko who replaced conventional genetics by his own “science” that fitted Marxist dogma. He rose to the top in Stalin’s favors at the expense of Soviet agriculture and mass starvation.”

“The Zika virus was undoubtedly introduced to Brazil by an infected traveller, just as such travellers are arriving in Europe from Latin America today.  And just as a drop of ink spreads on a piece of blotting paper, it is entirely normal to observe foci of transmission that expand from an initial introduction; we see such “clusters” time and time again with dengue and chikungunya.  We must also bear in mind that this problem is entirely urban, because that is where the mosquitoes live, so foci will also reflect populated areas.”

“Those who seek to stigmatise Oxitec conveniently ignore the full-blown epidemic of Zika in Tahiti.  This was first apparent in October, 2013 but, given many analogous epidemics of dengue, it is probable that the virus was already active for many months before.  Forty-two cases of Guillain-Barré syndrome and at least 17 cases of microcephaly have been identified.  In other words, if Oxitec were to blame for these cases, we must conclude that not only did the mosquitoes fly nearly 11,000km from Brazil to these remote islands, but they could fly backwards in time!

“The claim that the Oxitec mosquitoes have somehow modified the Zika virus is absurd, equivalent to finding coconut trees thriving on Mars.”

The Genetic Expert News Service (GENeS) in the US has collected expert commentary examining the potential effectiveness of Oxitec mosquitoes in limiting natural population numbers.

Dr. Thomas W. Scott, Distinguished Professor of Entomology and Epidemiology, University of California, Davis (webpage), comments:

“Results from field trials in Brazil for Oxitec’s existing genetically engineered mosquitoes are encouraging. The big challenge for this approach is logistics. How do you scale this system up to the huge areas and cities that need to be treated? I have not seen a clear, convincing answer to this critical question. And there are other questions: is the cost-effectiveness of this approach within reach of governmental budgets? And how sustainable will it be over broad geographic areas and densely populated modern mega-cities?

“Creating gene drive systems has been one of the key road blocks for genetic strategies of mosquito-borne disease control. New results using the CRISPR-Cas9 system are very encouraging, but they are currently lab based. It would be a gamble, and one I would not be comfortable taking, to start releasing CRISPR-modified mosquitoes into natural settings without a series of properly designed incremental studies that assess how well it performs in the field. Circumstances in the field are well know to be very different from well controlled lab settings, and can produce unexpected results.  Prior to use in a public health system we need to know from rigorous, properly designed studies how well a gene drive system in mosquitoes would work at preventing human infection and disease. To do this correctly, takes time and careful evaluation. Rushing to field application would be risky business.

“Overall, some of these techniques could hypothetically be used to eliminate diseases by making the mosquito species on which the diseases depend go extinct. But there are caveats. Removing some species could open a niche for others to occupy, and the result of that change are hard to predict. Another big question is whether elimination of a mosquito species is feasible. There are probably a few species we could eliminate with huge budgets and teams of people, but for the species that constitute the biggest public health problems I’m doubtful that with current tools eradication is feasible. Hopefully genetic strategies will evolve in their design and impact so that they can be effectively deployed for disease prevention in the future.”

Dr. Anthony James, Distinguished Professor, Microbiology & Molecular Genetics, University of California, Irvine (webpage), comments:

“Over a decade has past since the Oxitec mosquitoes were developed for population suppression. Improvements on that design could be made by using gene drives that would promote better efficacy and shorter times to impact. New strains could be made in less than a year but would need to be and tested in a phased program for efficacy and safety. The testing and scale-up would take 2-3 additional years, including meeting the regulatory requirements and necessary public engagement to get community consent to test them.

“Both Aedes aegypti and Aedes albopictus are not native to the Americas so eliminating them is a form of bioremediation. Gene drive technologies are the best and safest chance of getting elimination, with the fewest anticipated non-target effects and are a realistic solution for targeting specific problems; in this case, transmission of viruses (dengue, Chikungunya and Zika) by the major invasive Aedes species.”

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