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Skip to 0 minutes and 13 seconds One thing about Zika is that it is a new disease in the sense that it has arisen very recently and there are many things that we don’t know about yet. And that’s something that we have to accept, but also see as an opportunity to investigate new things to try and find out more about the disease so that we can control it better.

Skip to 0 minutes and 33 seconds One of the things when it comes to vectors is and this beloved of controversy over whether other species might be vectoring the disease so we know Aedes are important vectors, but it could be that other species are vectoring Zika as well, for example Culex mosquitoes, and there’s a bit of been a bit of discussion around that topic quite recently. And some studies are being done to try and define whether Culex are involved in the transmission, but at the moment we don’t know whether that is the case and more studies are certainly needed.

Skip to 1 minute and 3 seconds Another thing that we need to know about is how do we determine the risk of Zika in communities by using entomology by using potential indicators so, for example vector density – how many mosquitoes are there – by looking at the larvae or by looking at adult mosquitoes, and also by looking at the infection rates in those mosquitoes as well to determine what the risk of infection is within a particular community.

Skip to 1 minute and 32 seconds Those been well defined for certain diseases like dengue and we know more about dengue and malaria and other diseases like that, but for Zika, again there’s a lot of unknowns and we need to define those parameters so that we can better assess the risk of Zika in the countries that have the disease at the moment. Now we know that the humans obviously get Zika, but we also know that animals can harbour the disease as well and these are called reservoir hosts. And it’s very important that we understand which animals may be harbouring the disease, for example we know that primates are important.

Skip to 2 minutes and 3 seconds And in South America and other parts of the world you have a big overlap between human populations and animal populations, so we need to understand more about which animals might also be harbouring the disease as a reservoir hosts and therefore having an impact on the transmission of the disease. Another thing that we don’t quite understand about the Zika virus is whether it can be transmitted transovarially, so whether it can be transmitted from the mother, from the female mosquito, to the eggs and then the eggs hatch out and the young mosquito larvae and then the adults that they emerge into have the disease as well. This is possible for other types of viruses.

Skip to 2 minutes and 45 seconds We don’t know whether it’s possible for Zika at the moment and that’s something that needs to be investigated further. Now when it comes to vector control itself, again there are many unknowns, and we’re in a position where we have done many years of vector control on many diseases yet we really do lack good evidence and that’s usually because the studies that have been done have not been done to a particularly high standard or got the right data to be able to allow us to make good recommendations. So going forward, when we’re doing these intervention trials and we’re looking at vector control, we need to design these studies properly.

Skip to 3 minutes and 22 seconds What we need are large randomised controlled trials using the technology some of these technologies will be old technologies that we might think are of no use, but actually might be if we investigate them in the right way or combined with other technologies and some of these technologies will be new technologies like GM mosquitoes or Wolbachia for example, so we need to generate the evidence to be able to make the right recommendations. But it’s a bit of a tricky area really because you know some people are of the mind you know we should just go with what we think is the right thing and roll it out why are we wasting time generating data?

Skip to 3 minutes and 58 seconds But on the other side it is important that we have the data, the right evidence to be able to make the right recommendation without making mistakes that we might see further down the line. But how much data you need is a big question, and that is something that that we as scientists need to tackle and we need to be able to generate the right data to be able to make the right recommendations. There’s a number of cohorts being conducted now and there

Skip to 4 minutes and 25 seconds are essentially two types of cohorts for pregnant women: one is a cohort of pregnant women who already have a rash so we identify them at the rash, we test them to see if it’s Zika and then we follow them up. There’s already been there are some studies already reporting – there was a preliminary study in the New England. We followed 40 women and estimate 29% risk of congenital Zika syndrome, so it’s very high. But there are many other studies and it’s important that there are many different studies, because we need to find out if the risk is the same or if there are cofactors, for example previous dengue might change the risk of congenital Zika syndrome.

Skip to 5 minutes and 7 seconds So the cohorts are very important and so there are cohorts of pregnant women with a rash, but then there are also cohorts of pregnant women without a rash. So women who are pregnant are followed during the whole of their antenatal care and tested every month or so to see seroconversion and and those cohorts will look at the risk of congenital Zika in women who have Zika infection, but not clinical infection during pregnancy and that’s an important question. Whether the clinical symptoms are important for congenital Zika syndrome or not, because that has major implications for how you manage this during antenatal care.

Skip to 5 minutes and 47 seconds So the cohorts will also provide information on the spectrum of the syndrome and they will also provide information on how early can you detect microcephaly. So it’s doing repeat ultrasounds and then identifying babies with congenital Zika syndrome and looking back at the ultrasound and identify what. aspects in the ultrasound can be detected and how soon and that again will be important for personal choice more than almost anything. And I think the next set of important questions are about the impact of congenital Zika syndrome in countries where it has been present.

Skip to 6 minutes and 26 seconds I think aspects that need to be looked at are impact on the families, so impact of pregnancies even before they have Zika, how do women feel about pregnancy at the moment.

Skip to 6 minutes and 40 seconds And just a personal experience: in Brazil, before the epidemic you look at a pregnant woman and you feel so benevolent and happy for them and during the epidemic you see a pregnant woman and you worried about them. Is this baby going to be normal? So I think the experience of being pregnant during an epidemic of congenital disease like that is very very different. So trying to understand how that impact in the experience

Skip to 7 minutes and 6 seconds of the woman: just being pregnant during the epidemic, a diagnosis of Zika infection during pregnancy, and then very importantly, the impact of having a baby with microcephaly or mild forms of congenital Zika syndrome. Again, just observation of a few cases, the impact can be very very severe; marriages break up, almost all women we talked to lost their jobs because caring for a severely disabled child is a full time job.

Skip to 7 minutes and 42 seconds A sense of bereavement, a sense of disappointment of loss and trying to cope with children can be very difficult; many children are very irritable, cry 24 hours a day so parents barely can sleep. So there are very major impacts on the life of the women and the family, and I think it’s very important to document that. And then the second aspect is the burden on the health services.

Skip to 8 minutes and 9 seconds These are children that need to be seen by doctors and they need to have their neurological manifestations controlled and monitored and then they will have disabilities, hearing and sight, cognitive performance, would they be able to be cared for at home or would they need additional care, so there is a whole issue of impact on the health services. Of caring for the children, there’s also the impact of just having to diagnose all of these kids. So there’s the whole impact on health services, and then just the costs, the cost to the family, the cost to health services, the cost to society with having so many of the parents leaving work for example decreases productivity.

Skip to 8 minutes and 50 seconds So there’s a large issue of understanding the impact, and I think that that’s a very important new epidemiological question.

Gaps in our knowledge: entomology and epidemiology

There is a lot that we don’t know about the effects of Zika virus disease in the short, medium, and long term. How do we need to target our research efforts in order to close these gaps in our knowledge and become better prepared to fight vector-borne diseases like Zika?

In the first of two steps exploring some of the areas in which further studies are required, Professor James Logan discusses the entomological unknowns regarding Zika. He highlights our need to discover whether multiple species of mosquito are a vector, the use of entomological indicators to assess the risk of transmission within communities, animal reservoirs of the virus, and if it is transmitted from a female mosquito to her offspring. How could the evidence base for vector control methods be improved and expanded, and should we be aiming for elimination or control of Aedes?

Aedes mosquitoes are thought to be the primary mosquito species driving infection, but the virus has been isolated from many mosquito species, including field-collected Culex and Anopheles species.1

Laboratory studies have shown that Aedes aegypti and Aedes albopictus are able to become infected and transmit Zika virus, but suggest that Culex pipiens mosquitoes are not able to become infected. In the laboratory Aedes triseriatus were susceptible to infection when exposed to mice with high viremia concentrations, but were not found to be capable of transmitting the virus.2

Further studies have concluded that Anopheles gambiae, Anopheles stephensi, and Culex quinquefasciatus mosquitoes likely do not contribute significantly to Zika virus transmission to humans. However, we cannot rule out that anthropophilic mosquitoes of other species could be competent vectors.3

Recently, Ae. albopictus adults that were collected as eggs from Camaçari, Bahia, Brazil, in 2015 were found to be positive for Zika virus RNA. Whilst attempts to isolate live virus were not successful, this study suggests that Ae. albopictus may have had a role in Zika epidemiology in Bahia, Brazil, in 2015. It also raises the possibility that Zika may be transmitted vertically, or transovarially.4 Vertical transmission has been observed for dengue, yellow fever, West Nile, Japanese encephalitis, and St. Louis encephalitis viruses in several species of mosquitoes.5 A laboratory study published in November 2016 found evidence for vertical transmission of Zika virus in Ae. aegypti after intrathoracic inoculation but not for Ae. albopictus.6 Vertical transmission may provide a mechanism for the virus to survive during adverse conditions.

Despite the recent findings, there is not enough evidence to suggest that species, other than Ae aegypti and Ae albopctus, are implicated in the transmission of Zika. Therefore, control efforts remain targeted at those species.

From an epidemiological perspective, in this step Professor Laura Rodrigues reflects upon the lack of understanding of the medical effects of congenital Zika syndrome and the impact it may have on families, communities, and healthcare systems. She describes the studies that are being conducted, the information they will provide, and why this information will be useful in the future.

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Preventing the Zika Virus: Understanding and Controlling the Aedes Mosquito

London School of Hygiene & Tropical Medicine

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