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expert reaction to study on the genome analysis of the Zika virus outbreak in Brazil

The current outbreak of Zika infection in South and Central America is the focus of much research and a paper published in the journal Science has attempted to work out when Zika virus first arrived in Brazil. The research team report that the first human infection with Zika was detected in November 2015 and that introduction to Brazil probably occurred between May-December 2013.

All our previous output on this subject can be seen here.

 

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

“It’s highly plausible that Zika found its way into Brazil through single infected person or infected mosquito or its larvae, and that’s what this study points towards. However equally likely is that many infection sources were introduced at the same time but only one of these went onto start the Americas and Caribbean epidemic.

“It certainly doesn’t take much for a virus that is perfectly adapted to infect humans to spread provided the conditions are ideal – and in the case of Zika it found a population that had never seen the virus before and so had no immunity to it, and also a bountiful supply of the insect that it needs to spread. And that last point is really important – the range of the Aedes mosquito will limit where these explosive outbreaks can occur, and the UK is free of that mosquito.”

 

Prof. Martin Hibberd, Professor of Emerging Infectious Diseases, London School Of Hygiene & Tropical Medicine, said:

“This paper is the first to publish whole genome data from Zika virus in Brazil. It gives good new insights into the outbreak such as the predicted introduction time, although the number of genomes reported is very small. Many more are needed to get a more comprehensive picture of how the virus is spreading through Brazil and South America. Although not conclusive, it is an important step towards future work that will allow us to understand this outbreak in greater detail – work that will hopefully lead to more accurate intervention strategies.

“The introduction of one Zika virus leading to a widespread outbreak may seem surprising. However the modelling of other Zika outbreaks, and also the highly related dengue outbreaks, suggest that this is not unusual. In the right conditions, with sufficient mosquitoes and closely packed humans, the virus can spread rapidly.

“Given the amount of human travel between countries, any region with dengue could suffer from Zika. That means 3.6 billion people from the tropical regions are at potential risk. However the UK is not one of them. Our colder climate means the mosquitoes which transmit Zika and dengue are not found here. So, although it seems that in rare cases there can be sexual transmission of Zika, the UK is highly unlikely to experience a Zika epidemic. The cases seen in the UK will be from travellers returning from countries affected by Zika.”

 

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

“Faria et al have produced the first detailed analysis of the evolution of Zika virus as it crossed the Pacific Ocean and entered the Americas. One of their basic findings is the striking observation that the molecular clock of Zika virus – meaning the rate at which the virus evolves – is very regular indeed, even as far back as the first Asian sample, collected in Malaysia in 1966. This metronomic ticking of Zika evolution allows the authors to calibrate crucial dates in the story of Zika’s global voyage, in the process overturning a few of the general assumptions that have been made up till now. The first of these is the time that Zika arrived in Brazil. Faria et al estimate that it probably didn’t happen during the 2014 World Cup, as much previous speculation had hinted at, but was mostly likely several months earlier at least. An alternative candidate introduction event – another football tournament, the 2013 Confederations Cup – occurred before the Zika epidemic really got started in Polynesia. Since the evolutionary trees produced by Faria et al support (although cannot absolutely prove) that Zika arrived in Brazil from Polynesia, it seems likely that no specific sporting event is to blame.

“Another issue that the study helps clarify is whether or not any of the recent evolutionary changes in Zika virus are to blame for microcephaly. Although the evidence for Zika as the cause of microcephaly is growing, absolute proof is still not available. However, working on the assumption that Zika is the cause of microcephaly, one obvious next question would be: has some recent genetic change in the virus generated this new symptom? Faria et al show that samples from microcephaly cases are distributed around the evolutionary tree, which strongly argues against (although again can’t absolutely disprove) this idea. If microcephaly was being driven by some particularly nasty mutation, the cases would be more clustered together (on the tree, if not necessarily in space and time). If Zika is the cause of microcephaly (and at the moment this looks increasingly likely), then a more subtle interaction between virus, patient and environment is involved, rather than some new property arising within the virus due to mutation.

“Furthermore, the paper looks at the mutational pattern in general and concludes that few of the evolutionary changes seem to be in places in the Zika genome that would cause much consequent alteration in the virus’s behaviour. As we accumulate more genome sequences from both the Brazilian and Pacific Islands outbreaks, as well as from their cousin Zika viruses in South-East Asia, the picture now outlined by Faria et al will begin to be really fleshed out with more detail.”

 

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

“If Zika was introduced to Brazil in mid-2013 it suggests the virus has been circulating undetected for a long period of time: the first case reports in the country were in 2015. Similar infections like dengue fever also circulate in the region, so Zika infection can often be misdiagnosed. This could make it harder to understand the potential relationship between Zika, microcephaly and other neurological complications in South America and other regions. The analysis demonstrates the importance of collecting and analysing genome sequence data in real time. It is commendable that the authors posted their initial results online before publication, to aid other researchers working on Zika.”

 

Prof. Mark Woolhouse, Professor of Infectious Disease Epidemiology, University of Edinburgh, said:

“The paper by Faria and colleagues in Science improves our understanding on the Zika virus epidemic by comparing the genome sequences of 7 viruses from Brazil to other Zika viruses obtained a year or more ago from the Pacific Islands. The data were consistent with the hypothesis that Zika virus entered Brazil from the Pacific Islands in 2013, implying that it was circulating in Brazil for many months before it was detected. Virus genomes are constantly changing, but the researchers found no evidence that the strains now present in the Americas have different characteristics from previous Zika virus strains. The implication is that the current epidemic is the result of a familiar virus invading a new geographical area where conditions for it to spread are highly favourable, with high densities of people who have never been exposed to Zika virus before, and large numbers of the mosquitoes which transmit the virus.

“This useful contribution underlines the value of routine surveillance of Zika and other emerging viruses: we can learn a lot from genome sequencing but that can happen only if surveillance systems are in place to detect and sequence the viruses. If this were done more systematically and on a global scale then we would be better placed to detect outbreaks early and implement effective interventions.”

 

Zika virus in the Americas: Early epidemiological and genetic findings’ by Faria et al. published in Science on Thursday 24th March. 

 

Declared interests

Prof. Jonathan Ball: No conflicts of interest

Prof. Martin Hibberd: I have no direct conflict of interest, although I do have funding related to Dengue virus sequencing, with funding from various charities and commercial companies such as J&J and recent funding from the MRC Newton fund to sequence Zika viruses in Cape Verde.

Dr Derek Gatherer: No relevant conflict of interest

Dr Adam Kucharski: No conflicts of interest

Prof. Mark Woolhouse: I have no conflicts of interest to declare.

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