Reports in Time magazine today (Jan 13, 2015) about Insecticide Resistance in Mali shouldn’t really come under the heading of news. We’ve known about insecticide resistance in mosquitoes for a long time. In fact, that’s one of the reasons IVCC was set up in 2005—to develop new and effective vector control tools to challenge insecticide resistance.

But what is more serious is the comment in the article that resistance has ‘reached a level at some localities in Africa where it is resulting in the failure of the nets to provide meaningful control’. This is not only inaccurate, it is positively harmful.  Even if insecticides on bednets shows limited efficacy in some cases, the physical barrier of the bednet still provides a meaningful level of protection—over 50% according to WHO.  The article also fails to point out that the impact of growing insecticide resistance is not yet fully understood, nor is it distributed evenly across sub-Saharan Africa.

Long-lasting Insecticidal Treated bednets (LLINs), and Indoor Residual Spraying (IRS) have been remarkably successful over the past 15 years in reducing deaths and sickness from malaria across sub-Saharan Africa. In the World Malaria report 2015, the WHO reports that malaria mortality rates have decreased by 54% in the region during this period and that 44% of the population at risk is now sleeping under a LLIN. They estimate that 670 million fewer case and 4.3 million fewer malaria deaths occurred between 2001 and 2013 than would have occurred if incidence and mortality rates had remained unchanged.

Undoubtedly, some of this is due to better drug therapies and more effective diagnostics and health systems and that is also good news. But a large portion of it is also down to effective protection of the people at risk, especially the most vulnerable groups of pregnant women and young children. There is substantial evidence that LLINs and IRS have been remarkably efficient. The massive distribution of bednets has been a major lifesaver.

Ironically, the success of bednets and IRS one of the reasons why resistance has been developing. It’s a natural response from an insect population under stress. (See our video ‘The Tipping Point’) And it’s why we’re developing new anti-malarial insecticides that are safe for people and the environment that could bring to an end this never ceasing circle of solution-resistance-solution. (See our video ‘Why 3 new Ais’)

Working with the world’s leading agro-chemical companies, and top scientific experts in entomology and chemistry, we have already isolated 9 new chemical classes of anti-malarial insecticide with completely new (and different from each other)  modes of action. This year we will select 3 of these to go into full development. If funding is adequate and the extensive regulatory processes are passed, these new insecticides will be in operation in the field by 2022.

In the meantime we have developed new formulations of existing insecticides for IRS, and have some novel approaches to bednets that are currently undergoing evaluation.

Time reports scientists are urging ‘the development of new and effective malaria vector control strategies’. Right, we’re on the case and the finishing line is in sight.

A personal view of the Stakeholder Day 2014, by Journalist Stephen Regan

In his keynote speech toward the end of the forum Dr Alan Magill – Director of the Bill and Melinda Gates Foundation – told delegates: “I have probably the world’s shortest job description. It is two words – Eradicate Malaria. Bill and Melinda are very clear and direct in their communication.”

Dr Magill also proved clear in his communication, making a cogent, detailed case for moving away from control strategies for malaria – to eradication. Control of malaria, as we’d come to understand it over recent years, was left with very few tools and very few strategies, he told delegates.  He named some of those tools and strategies – long-lasting insecticidal-treated nets, IRS with a few different compounds, first generation malaria rapid diagnostic test, ACTs to treat sick people and a few interventions within that preventive treatment.

He acknowledged that applying the limited sets of tools at scale over the last decade or so had led to some remarkable achievements.

But he added: “This control paradigm clearly has … weaknesses.  And one of those, of course, is that these interventions really need to be applied continuously and with great vigour for a long time”.

There was no apparent exit strategy, he observed, and applying the current set of tools for a very, very long time means we will to lose the tools to resistance. That was already happening.

Dr Magill said: “We’ve used the tools … and stratagems we have, in an evolutionary incorrect and ecologically incorrect way for quite some time.”
He predicted that that would be noticed in the funding round-up for replenishment next year, and added: “Every disease, every topic, has its moment in the sun.”

He asked delegates to recognise that eradication of malaria is actually the only pathway forward and to get behind the campaign to Accelerate to Zero. He defined malaria eradication as “actually getting parasites out of people”.

Principles

Dr Magill outlined five principles: the importance of precise definitions; complete cure (as opposed to what he called “clinical cure”); tackling the transmission reservoir in asymptomatic people; think global – act local; and approaching everything we do with the fundamental precepts of evolutionary medicine and correct ecological thinking. Of that final principle he said: “Malaria is a very big, complex system. It’s got the biology, the ecology, the political and the social pieces.”

He said: “Probably 90 percent of the parasite biomass is in people who are not infected, who are not ill, who are not coming to you, and today we do nothing about these people, nothing at all.  We’re playing defence, to take an American sports analogy.  We’re just sitting back in health care clinics waiting for sick people to come to us and treat them.  We need to turn the game a little bit and go on offence and go out into the community, finding people and treating them so they can no longer transmit.

The Accelerate to Zero strategy was about complete cure, he said: about finding infected people, completely curing them and getting parasites out of the population, combined with complete prevention – i.e. effective transmission prevention. With it went the goals of preparing for the future and sustaining progress.

Dr Magill spoke of the need to create a good environment for the manufacturers who will deliver the new products needed.

He also addressed the need for entomological intelligence when trying to close transmission gaps in territories such as Cambodia, and the need to build an effective value chain in vector product development.

Finish the job

Dr Magill finished with a rallying call: “Let’s finish the job if you will.  We don’t like to get distracted by discussions about elimination and eradication. This is all about saving lives.  It’s saving lives now in sick people and it’s saving lives for ever going forward because we’re going to avert all those deaths by elimination. It’s a pure, simple equation.  We know that this is biologically and technically feasible and we think the new tools that will be developed in the next few years will make a lot of the things we’re talking about much more operational and feasible.

“We think this next decade will be an intense period of experimentation. This is about using current tools and new ways, and really thinking about that long term goal of eradication.

“We’re building an eco-system, as I call it – the eradication eco-system. As Admiral Ziemer said, we cannot do this by any one group or any one method. This really requires a big team. And putting these hubs together and finding out at the product development level, the implementation level, the political level, well, you can see that it’s actually so complex it’s even hard to imagine.

“But we know that this is essentially a group going forward, and I’ve taken the advantage here to say IVCC is a hub in the eradication eco system, and through that hub we can reach out to all the talent in the room.

“I would say that if there’s a problem out there in the vector space world, well this is the group of people to solve it.  You own it; if you don’t like it it’s up to you to change it.”

IVCC is to lead a consortium of partners on a ground-breaking project funded by Unitaid and the Global Fund to bring to market new versions of insecticide-treated bed nets to fight malaria-carrying mosquitoes that have become resistant to older insecticides. It is hoped that the nets will provide a stronger line of defence against malaria for millions of people.

The New Nets Project, signed in Geneva yesterday will pilot long-lasting insecticidal bed nets treated with new insecticide combinations in sub-Saharan African countries hardest hit by malaria.

The Global Fund and Unitaid will each contribute US$33 million to the four-year project. The coalition, consisting of PATH, Population Services International (PSI) / Alliance for Malaria Prevention (AMP), London School of Hygiene and Tropical Medicine (LSHTM), with support from Imperial College London, Liverpool School of Tropical Medicine, and Tulane University, will run between 2018 and 2022.

The project will build the evidence needed to allow WHO to consider making new policy around the use of these nets and will also assess their cost-effectiveness under pilot conditions.

The production volumes procured for the pilots will help the project to negotiate significant price reductions. These reductions are needed to make the new nets a sustainable choice for countries looking for the best value for money in controlling malaria.

Nick Hamon, CEO of IVCC said; “The continued success and impact on lives saved of the NGenIRS project means that IVCC is well positioned, with its project partners, to demonstrate the public health value of new dual active ingredient bed nets and deliver radically new solutions to combat the growing threat of insecticide resistance which is prevalent across malaria endemic countries.

Unitaid’s Executive Director Lelio Marmora added: “Working with partners such as the Global Fund, we can leverage the effect of our innovations, such as new insecticides and new insecticide-treated nets,” said “Together we can make a powerful impact against malaria.”

Mosquito nets provide a physical barrier against mosquitoes and treating the nets with insecticide makes them lethal for mosquitoes that land on them. One of the most effective means of preventing malaria is sleeping under a long-lasting insecticidal net.

Mosquitoes’ resistance to insecticides threatens to undermine progress against malaria. Although the number of new malaria cases has fallen dramatically over the past 15 years, progress has recently stalled. According to the World Health Organization, there were 216 million cases of malaria worldwide in 2016, 5 million more cases than the year before.

A child dies of malaria every two minutes, although the disease is preventable and curable.

“By investing in insecticide-treated nets and other tools, the Global Fund partnership has greatly reduced the burden of malaria,” said Peter Sands, Executive Director of the Global Fund. “This project is a step toward accelerating impact by embracing innovation – with the ultimate goal of malaria elimination.”

The New Nets Project will support the WHO’s malaria goals, which aim by 2030 to reduce malaria cases and deaths by 90 percent, eliminate the disease in at least 35 countries and prevent a resurgence in countries that are malaria-free.

IVCC is leading another Unitaid-funded initiative, the US$65 million NgenIRS project, which is ushering in new long-lasting indoor residual insecticide sprays to replace less-effective older chemistries and formulations. Unitaid’s work against malaria extends to the Asia Pacific Region, where it is collaborating with the Asia Pacific Leaders Malaria Alliance (APLMA) on the Vector Control Platform for Asia Pacific (VCAP), a collaborative platform to improve access to new vector control tools.