Zika virus is the latest vector borne disease to hit the headlines. It is primarily transmitted by infected mosquitos, but one of the reasons it’s been in the headlines is that it can also be transmitted by sexual contact.

There’s also great concern because of the links to Zika virus and microcephaly, a medical condition in which a baby is born with an abnormally small head, which can lead mental and other complications. Menacing, especially as you can have the virus without being aware of it.

The jury is still out on the specifics of how the virus is spread but there is clear evidence that the main culprit is the mosquito — in this case the species Aedes aegypti, which is also responsible for transmitting yellow fever, dengue fever and chikungunya. It’s reported that the mosquito can bite four or five people in the course of one blood meal, meaning that it can be spread very rapidly. The virus has already been reported in many Latin American and Caribbean countries and some reports suggest as many as 1.5 million people may now be affected.

So Zika virus joins malaria as a threatening mosquito-transmitted disease. There is all manner of crazy speculation around as to how the disease has become so prevalent — it was first identified in Uganda as long ago as 1947. As you would expect with a story that has all the potential elements of media hype, there’s a lot of ‘quackery’ (as one eminent entomologist described it) flying around about about the origins of the current outbreak. So far there is no scientific basis for any of this, but the speculation prompted the WHO to state categorically that there is no evidence linking Zika to genetically modified mosquitos.

So what do we know? To save me repeating what has already been written, consult the briefing paper below:

Zika Virus, Vector Control and IVCC.

IVCC is delighted to support the inaugural “World Pest Day” launched in Beijing on 6th June 2017.

Initiated by the Chinese Pest Control Association and with the support of the World Health Organization (WHO), the Federation of Asian & Oceania Pest Managements Association (FAOPMA), the National Pest Management Association  in the USA (NPMA) and the Confederation of European Pest Management Associations (CEPA), the aim of the day is to raise awareness of the devastating impact of pests around the world.

Mosquitoes, are just one of many vector borne pests capable of carrying deadly diseases. Today, there are 2.5 billion people in more than 100 countries threatened by diseases such as dengue, yellow fever, chikungunya, schistosomiasis, dysentery and typhoid.

IVCC continues to develop strong ties with China.  In November 2016 Liu Qiyong, Director, WHO Collaborating Centre for Vector Control Surveillance and Management and current IVCC Board member, hosted a visit by IVCC CEO Nick Hamon to China CDC.  There they discussed novel vector control solutions for Aedes mosquitoes due to their widespread insecticide resistance in the region.   IVCC also invited China CDC to visit the Bill & Melinda Gates Foundation office in Beijing to advocate for China’s continued investment in vector control projects.

There are thousands of species of mosquitoes that feed on the blood of a wide range of hosts including mammals, birds, reptiles and amphibians. Though the loss of blood seldom debilitates the hosts on which they feed, the saliva of mosquitoes can often result in an immune reaction, leading to a rash. Much more serious though, are the diseases that mosquitoes can transmit through their bites. In moving between their hosts, some mosquitoes transmit extremely harmful diseases affecting humans such as malaria, yellow fever, Chikungunya, West Nile virus, dengue fever, filariasis, Zika virus and other arboviruses.

I first became involved in research on mosquitoes and their control in 1983 when, as a final year undergraduate at the University of Dundee, I did a short research project on the biological control of the yellow fever mosquito, Aedes aegypti, using the ‘elephant mosquito’, Toxorhynchites brevipalpis. Toxorhynchites is a fascinating genus of mosquitoes with a wingspan which can exceed 12 mm. Fortunately, the large adult mosquitoes feed only on nectar and fruit juices. Better still, the larvae are predatory on other aquatic insects including other mosquito larvae.

Since the introduction of DDT in the 1940s, mosquito control programmes have used large amounts of insecticides from different insecticide classes in order to reduce or eradicate mosquito vector-borne diseases. In response to this insecticide selection pressure, mosquitoes have evolved several different mechanisms to resist their effect. The main two types of mechanisms found in mosquitoes are: mutations in the genes of the target site of an insecticide class, leading to target site insensitivity; and changes in the metabolic enzymes inside the mosquitoes meaning that insecticides are broken down before they can have their effect. It was the latter mechanism of resistance that was the subject of my PhD at the London School of Hygiene & Tropical Medicine during which I purified and characterised esterase enzymes associated with insecticide resistance in populations of the southern house mosquito, Culex quinquefasciatus, from Cuba and South America.

Whilst I continued to conduct research on mosquitoes off and on since the completion of my PhD, it wasn’t until very recently that I fully devoted my career to working on them. In 2010, I had what one might call a career epiphany moment, when I decided that I wanted to devote the rest of my working life to the control of mosquito vectors of malaria. As part of a consultancy with IVCC, I was visiting facilities in West Africa conducting vector research. One of the facilities we visited was IRSS/Centre Muraz in Bobo-Dioulasso, Burkina Faso and, during this visit, we went to a village in the Vallée du Kou where they were running a community trial on a new long-lasting insecticidal net (LLIN). As I stood outside one of the village huts, a group of children congregated to see what all of these strangers were doing in their village. We smiled at each other and waved. Then, as we left the village to drive back to town, I learnt that the number of infected mosquito bites these children received every year are in the hundreds and that malaria is the main cause of morbidityand mortalitywith children in the area. This was my motivation for wanting for wanting to join IVCC and, I’m very happy to say, I became a member of the IVCC team in December 2016.

Zika virus was discovered decades ago but wasn’t associated with birth defects until the 2015–2016 outbreak in Brazil. Research by Ling Yuan and colleagues in China, published in Science on 28th September 2017 (A single mutation in the prM protein of Zika virus contributes to fetal microcephaly),  demonstrates that a single point mutation that occurred in the Zika virus in 2013, before an outbreak in French Polynesia, may have been responsible for this virus starting to cause microcephaly (abnormally small head size).

Since the shocking increase in birth defects linked to Zika virus infection was discovered, congenital Zika syndrome has spread to many countries but overall numbers have not increased as rapidly as feared (the Pan American Health Organization reports 2,074 confirmed cases of congenital Zika syndrome in 2015 and up to the end September 2016 and a further 1,615 in the last 12 months). Zika has fallen out of the headlines and is no longer classified by the World Health Organisation as a ‘PublHealth Emergency of International Concern’. Does this mean the problem has gone away and all our attention is now elsewhere? Certainly not!

The problem has certainly not gone away for the children affected by Zika virus or for their families. Congenital Zika syndrome encompasses more than microcephaly. Other symptoms are decreased brain tissue, damage to the back of the eye, joints with limited range of motion and too much muscle tone restricting body movement soon after birth. Some children develop symptoms later and may not exhibit microcephaly at birth.

Nor has the problem gone away for people living in more than 90 countries where Zika virus is present or for travellers to these countries. Currently there are no licensed vaccines or therapeutics available to combat Zika and the advice from the US Centers for Disease Control for pregnant women is to avoid travel to affected areas and for men to avoid unprotected sex with partners for 6 months after returning if trying to conceive (Risk of Zika Selected Destination). A Zika infection is understood to lead to immunity to subsequent infections and this may account in part for the slowing of the rate of growth of the impact of Zika on local populations in the affected zones. However, many young women within these countries have not yet been infected and remain at risk.

What about the research effort against Zika? Is that coming up with any solutions? There are currently over 30 Zika virus vaccine candidates in development. Last year, the Food and Drug Administration approved the first human testing of a Zika vaccine candidate, and this summer, a US$100 million US government-led clinical trial is underway. However, there are considerable technical and commercial challenges ahead, including the complex ethical issues involved in conducting large scale efficacy trials in pregnant women.

What about new methods for control of the mosquito that transmits Zika virus? IVCC is supporting 9 of the projects within USAID’s US$30 million Grand Challenge for Combating Zika and Future Threats. These are research projects run by academic groups based in 5 different continents. They are bringing forward innovations to improve the monitoring and control of the key vector species, the Aedes aegypti mosquito. I am privileged to have been appointed by IVCC to coordinate the support for these 2-year projects which started at the beginning of 2017. Amongst the exciting innovations are automated traps that will count and identify their contents and transmit this information, enabling early detection of the vector and a rapid control response. Four of the projects are creating invisible barriers that will prevent mosquito bites. There are also two projects on new, biological-based control systems.

Researchers at Duke University in the United States and UK based Product Development Partnership IVCC have proposed a new mechanism for stimulating public sector product development to fight malaria and neglected tropical diseases (NTDs). The Vector Expedited Review Voucher (VERV) is based on a similar proposal, called the Priority Review Voucher (PRV) that has been stimulating drug development in NTDs in the United States since it was first introduced in 2007.

“It’s about reducing inefficiency in the regulatory process, and using the gains to fix a market failure in product development to benefit society as a whole,” said David Ridley, a professor at Duke University’s Fuqua School of Business and part of the team proposing the voucher reward for approving new public health insecticides through the U.S. Environmental Protection Agency (EPA).

The team’s findings, “A Voucher System to Speed Regulatory Review Could Promote a New Generation of Insecticides to Fight Vector-Borne Diseases,” are published in the August edition of Health Affairs.

Nick Hamon, CEO of IVCC said: “Insecticides used in bednets and for treating homes have prevented millions of deaths from malaria and other diseases. But while the population of disease-carrying insects resistant to current treatments has grown, no new class of insecticides have been developed specifically for public health in the last 40 years because there is little profit opportunity to innovate in these markets.”

The Vector Expedited Review Voucher proposal would offer the company behind the new product an expedited regulatory review for a second, more profitable product intended to protect crops – as a way to encourage large agrochemical companies to invest in developing less profitable innovative products for public health use.

The VERV proposal is based on the system David Ridley, Jeffrey Moe and Henry Grabowski of Duke University proposed for the U.S. Food and Drug Administration a decade ago to encourage the development of treatments for neglected tropical diseases.

Congress made that proposal law in 2007. The FDA has issued 14 vouchers since that program began. They offer review of a drug in six months rather than the usual 10 months, which can make a huge difference to firms bringing a new product to market. Seven of the vouchers issued so far have been sold, fetching as much as $350 million.

“We brought a creative solution to drug development, and now we want to apply it to public health insecticide development,” Moe said.

Ridley and Moe partnered with Nick Hamon, CEO of the IVCC, a UK based not for profit product development partnership (PDP) that works to prevent the spread of malaria and other NTDs. IVCC is funded by the Bill & Melinda Gates Foundation, UKaid, USAID, Unitaid and The Swiss Agency for Corporation and Development (SDC).

“Medicines are an important tool in fighting these diseases, but they are not the only tool,” said Professor Moe. Whereas 65 percent of research and development funding for malaria was for drugs and vaccines, only 6 percent was for vector control, according to the paper. Similarly, the market for vector control insecticides is significantly less than $1 billion, while agricultural chemicals exceed $47 billion in annual sales. The development of a novel insecticide from discovery through to launch can cost between $100-$250m can take up to twelve years, making a return on investment in vector control almost impossible. Awarding a VERV gives an innovator company an opportunity to generate a financial return on an agricultural product as well as reducing the time to market of critically important products.

The Vector Expedited Review Voucher (VERV) proposal incorporates lessons learned through 10 years of the FDA Priority Review Voucher program, by proposing that ensuring that projects that gain a voucher are truly novel and will go where they’re needed.

“Not a week goes by in which we don’t discuss ways we can make the voucher review program better,” Ridley said.

Ridley, who also works with Duke’s Margolis Center for Health Policy, said he expects to see more of the vector review vouchers to be used by the companies that win them, because the industry is dominated by larger players that are less likely to sell to competitors.

“However, we might be surprised,” he said. “There could be companies we’ve never heard of that receive investor funding and develop products because of the potential value of a VERV. That’s one of the beauties of prizes like this – you don’t pick the winners in advance.”