February 4, 2016

expert reaction to continuing Zika outbreak, microcephaly clusters and mosquitoes

Further comments from experts on different aspects related to Zika, including microcephaly clusters and mosquitoes, as the outbreak continues to develop.

Dr Adam Kucharski, Research Fellow in Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, said:

“A number of congenital issues were observed in French Polynesia following the 2013-14 outbreak: http://www.hygiene-publique.gov.pf/IMG/pdf/note_malformations_congenitales_cerebrales.pdf

“Between March 2014 and May 2015 (the ZIKV outbreak ended in spring 2014), there were 18 cases of neurological complications in fetuses and infants. The sample size is obviously very small, and ZIKV tests often quite ambigious, so it’s hard to say anything conclusive. But Brazil certainly isn’t the first time an unusual pattern of neurological disorders has occurred following a ZIKV outbreak.”

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.”

Dr Nina Alphey, Mathematical Ecologist at the University of Oxford, said:

“Correlation is not causation, i.e. finding two things occurring in the same circumstances does not mean that one must be causing the other. Zika virus, and any kind of control of Aedes mosquitoes, can only happen in places where those mosquitoes are. As others have pointed out, the GM mosquito trials occurred hundreds of kilometres – and in most cases years earlier in time – from the origin of the Brazilian Zika/microcephaly outbreak. As conventional mosquito control efforts (chemical controls and restriction of breeding sites) are rightly being stepped up in affected areas, those too will be even more strongly correlated with the disease clusters, but are not causing them.

“The tools currently available are failing to provide adequate control, and a vaccine is years away; genetics-based mosquito control is a potentially valuable addition to the toolkit, and has already gone through regulatory processes and successful field testing in Brazil. Unfounded scare stories have the potential to do harm if they influence the Brazilian authorities’ decisions on whether and how to incorporate new technologies into their action plans.”

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 (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4593458/) suggests that the genetic lineage of the Zika isolated in Brazil is closely related to that from French Polynesia (99% similarity; http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4593454/). 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, said:

“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.”

Declared interests:

Dr Adam Kucharski: “I have no interests to declare.”

Prof. John Edmunds: “No conflicts.”

Prof. Jonathan Ball: “No conflicts of interest.”

Prof. Bonsall:“I was the Specialist Adviser to the inquiry on Genetically Modified Insects by the House of Lords Science and Technology Committee, and am a member of ACRE (Defra’s committee on releases into the environment). The Advisory Committee on Releases to the Environment is independent scientific committee that through EU derivatives and national UK legislation is mandated to provide the UK government/ministers with advice on the environmental risks (to wider receiving environments/human health) of non-native and GM releases. I have been a member of this committee since December 2007. I have carried out occasional consultancy work for WHO, NIH, and EFSA, including work on GM-based control methods for mosquitoes. I have received research funding from BBSRC (including working with Oxitec on GM insects), Oxford Martin School, NERC, the Royal Statistical Society, and the Royal Entomological Society. For full details of all my interests, please see:
http://www.parliament.uk/documents/lords-committees/science-technology/GMI
nsects/michael-bonsall-specialist-adviser-interests.pdf”

Dr Alphey:“I had an indirect interest in the shares of Oxitec Limited; my husband had equity shares and options in Oxitec and now has equity in the parent company Intrexon Inc. Oxitec and the University of Oxford have patents or patent applications in the broad area of genetics-based methods of pest management. My research is funded by BBSRC, with Oxitec as industrial partner to the agreement.”

Prof. Reiter: “I am not in any monetary relationship with Oxitec. However, as a professional, I have been enthusiastic about their technology for many years and act as an advisor on mosquito biology and behaviour. My direct involvement with them has been as follows: In 2005 they funded a PhD student to work on male dispersal. He worked with the Asian Tiger mosquito (not a transgenic; there was none of this species). Most of his work was on Reunion Island (no Ae. aegypti there). Apart from their obvious interest in the results, Oxitec had no involvement in the study. I also had a post-doc who worked for two years in a laboratory study on mating behaviour of the transgenic vs wild type. She was mainly funded by the Institut Pasteur.” (Updated at the request of Prof. Reiter 17:47 04/02/2016)

Others: None declared