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Interceptor® G2 and Insecticide Resistance 14th July 2017

Although I have never lived in Africa, I’ve travelled there enough times to have a reasonable feel for the place. Urban Africa, busy, chaotic and unsafe contrasts enormously with the friendliness and warmth of Africans in rural communities, who despite their obvious hardship, will ask me to stop and share a cup of bitter tea with them.   The remote villages I visit lack many of the conveniences that we take for granted.   Mostly, there’s no running water, electricity is occasional and the air at dusk is filled with smoke as food is prepared and cooked in family compounds. Living is basic, but there’s a strange contrast between pinging money using mobile phones with crushing caterpillars to eat and livestock living amongst families with crowds gathering around flat screen TVs to watch Champions League football.

Life can be exceptionally tough.  Basic food may be available year-round for most so while there may be little excess it looks like no one starves.  There’s not much money and that’s ok when hard work is the main price for food, but the lack of access to a modern healthcare infrastructure can mean that when disease hits, there can be no money to pay for treatments, and this can devastate families and villages without warning.

90% of malaria cases occur in sub-Saharan Africa, and kills over 400,000 people every year – the vast majority of which are children under five.

Many villages have insecticide-treated bednets which provide proven malaria protection when sleeping at night. But there are never enough, mosquitoes can bite at times when no one is under their net and outside the home, and not everyone likes to use them.   Now and again when you ask if a householder has a bednet, they pull out an unused net, still in the bag to show.

Insecticide treated bednets not only provide personal protection through the physical barrier of the net, but the insecticide also provides effective community protection as contact with the net kills the mosquito meaning it can’t fly off and infect someone else.

However, this critical community effect which reduces the volume of biting mosquitoes, only works if the mosquito is not resistant to the insecticide.  Resistance is a huge issue today.  We are at a critical tipping point and without innovation in insecticide resistance, the huge gains in malaria reduction we have made since 2000 could rapidly unwind with devastating effect, but insecticide resistance is complex. There are different underlying mechanisms in different locations, species of mosquito and regions that impact the performance of different insecticides in different ways that makes measuring the benefits of different interventions on disease transmission complex.

That’s why the arrival of BASF’s Interceptor® G2 is so important.  This net introduces a safe and reformulated insecticide from agriculture into public health – a first in 30 years.  Because mosquitoes have not been exposed to it before, it will be effective against mosquitoes that are resistant to the insecticides that are commonly used on bednets.  Of course, this product alone will not solve the problem.  More resistance beating public health insecticides need to be developed and used in a way that preserves their effectiveness in the long term by developing and following resistance prevention strategies.

That’s why IVCC is working with companies across the world to develop new public health insecticides for bednets as well as new resistance beating formulas for spraying on the inside walls of homes, another proven and effective intervention.  We are also investigating a range of other technologies which will reduce outdoor biting.  We have a long way to go but we are hopeful that, together with our industry partners like BASF and our dedicated funders, innovation in vector control can help create a world without malaria.

IVCC Announces Game-Changing Mosquito Net 13th July 2017

The Innovative Vector Control Consortium (IVCC) is delighted to announce that, resulting from a collaboration with BASF and the London School of Hygiene & Tropical Medicine, a new type of Long Lasting Insecticidal Net (LLIN) has received a recommendation for use by the World Health Organization (WHO).

This new LLIN, Interceptor® G2, combines the current pyrethroid class of public health insecticide used in bednets across malaria endemic countries, with a repurposed insecticide from agriculture called Chlorfenapyr.  The successful mixture of these two active ingredients coated on a LLIN represents a major advance in the mission to overcome insecticide resistance.  Chlorfenapyr has a different mode of action from current WHO recommended public health insecticides.

Liverpool based IVCC played an instrumental part in bringing this product to the recommendation stage, supporting and funding the project during the field trials and, as project partner, leading the technical progress of the project through its External Scientific Advisory Committee (ESAC).

Nick Hamon, CEO of IVCC said: “Interceptor® G2 is a major step forward in the battle against mosquito insecticide resistance.  We hope and expect this to be the first of several novel vector control products IVCC will support bringing to market in the coming years to help eradicate malaria”.

“Developing new vector control tools would not be possible without the dedication of our industry partners and the visionary support of our funders.  Without the financial backing of organisations such as the Bill & Melinda Gates Foundation and UKaid, the complex development, testing and evidence gathering exercises needed to support novel vector control products would simply not be possible.  They, along with BASF, deserve immense credit.”

Dave Malone, Technical Manager at IVCC added; “The growing intensity and distribution of resistance to pyrethroids threatens to undermine the great progress that has been made against malaria by the use of LLINs, particularly in sub-Saharan African where 90 per cent of malaria deaths occur.  By combining pyrethroids with a new class of chemistry, these new LLINs have the potential to protect and save many more lives.”

IVCC Supports World Pest Day 6th June 2017

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.

Mosquitoes – A Personal Perspective on World Mosquito Day 20th October 2017

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 brevipalpisToxorhynchites 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.

A Proposal to Incentivize Innovation that Could Help Save Lives 8th August 2017

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.”

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