The underlying fact seems incontrovertible: mosquito resistance to the insecticides used to treat bednets is growing. The question is what can be done to combat this resistance and ringfence the dramatic drop in global malaria deaths over the past 15 years?

Since 2000, the numbers of people dying of malaria have dropped by 60% and cases of the disease have fallen by 37%, according to the World Health Organisation (WHO).

Insecticide-treated bednets, indoor and outdoor spraying, and other measures have averted millions of deaths, the WHO’s 2015 malaria report found. Research published in Nature and included in the report showed that bednets had been “by far the most important intervention” across Africa, accounting for an estimated 68% of cases prevented since 2000.

But the report highlighted concern about mosquito resistance to insecticides used in bednets or indoor spraying. The evidence of resistance to pyrethroids – the only insecticide class approved by the WHO for use in long-lasting bednets – has been building.

“Insecticide resistance is an important emerging threat that could potentially weaken malaria responses in many countries. Since 2010, 60 of the 78 countries that monitor resistance have reported [resilience] to at least one insecticide used in nets and indoor residual spraying,” a WHO spokesperson says.



“We do not, at this point in time, have sufficient evidence linking an increase in insecticide resistance to [cases] or death rates.”

Vestergaard, a Swiss firm that makes bednets, argues that it is time to change strategy. It is among a handful of firms to have developed a combination net to replace nets treated with pyrethroids.

Vestergaard’s new net contains piperonyl butoxide (PBO), with a pyrethroid insecticide in the roof section. PBO is a synergist that enhances the effect of the insecticide.

CEO Mikkel Vestergaard Frandsen says the new net was evaluated in 2007 by the WHO and by the Vector Control Advisory Group (VCAG), which serves as an independent advisory board to the WHO.

“In February 2014, they concluded: this product is recommended, it’s the first in class of a new tool in a new category of bednets,” Vestergaard says, accusing the WHO of dragging its feet in drawing up deployment guidelines for the new nets.

The WHO spokesperson says there is “nothing holding up the process for the rollout of PBO nets”, which, it says, are recommended for use where metabolic resistance – when mosquitoes use enzymes to break down the insecticides – is present.



Mosquitoes can develop metabolic or knockdown resistance (KDR), or both. Insects with KDR have mutations that prevent the insecticide from binding effectively with the target site in the nervous system.



The WHO says the VCAG only makes recommendations on efficacy of new tools, not on deployment. The WHO is advised by the independent Malaria Policy Advisory Committee on deploying new ways to battle malaria.

Vestergaard Frandsen says the WHO is missing a chance to get ahead of the next big health problem.

“I am convinced that insecticide resistance is the next global embarrassment for the WHO,” he says, “and I’m saying that because there are all sorts of possibilities to do something about it.”

The WHO’s spokesperson says: “There is only one insecticide currently recommended by WHO for the treatment of mosquito nets – pyrethroids … As such, the use of multiple insecticides for bednets is not possible at this time. Next-generation insecticide-treated nets with different classes of insecticides are being evaluated.”

Proving a causal relationship between mosquito resistance and deaths is very difficult, says Helen Pates Jamet, Vestergaard’s head of entomology.

“Looking for this definitive evidence from a randomised control trial – the gold standard of academia – is not an easy thing to do and it may never be possible because you can’t randomise resistance. Resistance changes over time … The concern is that, while waiting for the definitive data, the only way that we are going to get that is by seeing an increase in deaths and cases, before we have the definitive study that says this is the link.”

Another concern is that if people see that nets are not being effective, for example if mosquitoes are landing on them and not dying, they might stop using them, reversing years of work.

“If your bednet is no longer killing mosquitoes, then obviously the community effect – in terms of how widespread use of bednets can reduce the malaria in the mosquito population – will no longer be sustainable,” says Pates Jamet.

“There are increasing numbers of places where you see mosquitoes resting on long-lasting nets, fresh out of the bag, or on freshly sprayed walls, and more and more studies showing that pyrethroid nets are no longer killing mosquitoes in experimental studies, for example, as they were 10 years ago.”

Many countries in sub-Saharan Africa, from Senegal in the west to Ethiopia in the east, are at risk from growing resistance. Vestergaard has been mapping resistance in 64 countries since 1956.

Mosquito resistance to pyrethroids does not necessarily mean nets are ineffective. The WHO spokesperson says that even where there is resistance to pyrethroids, “mosquito nets have been shown to provide protection due to the physical barrier provided by nets, as well as other factors”.

In a study published in the journal Parasites and Vectors in March, researchers from the London School of Hygiene and Tropical Medicine and the Malaria Consortium found that bednets might still help prevent malaria, despite resistance to pyrethroids.

The research, carried out in Uganda and funded by UK aid, found that although resistant mosquitoes were surviving contact with the insecticide, parasites inside those mosquitoes were affected by the chemicals.

Lead author Mojca Kristan says: “Sub-lethal doses of pyrethroids, even when they do not kill mosquitoes, can affect the development of malaria parasites in them, which can potentially help reduce the transmission.”

“We recognise that insecticide resistance remains a major threat to malaria control. What our study indicated was that the pyrethroid-treated nets seem to remain partly effective despite increasing resistance through their effect on the malaria parasite.”

Vestergaard Frandsen, however, says the system is broken, and describes growing resistance as a “wakeup call” that evaluating a new product should not take longer than developing it.

“For us to stay ahead of the game in reducing global malaria deaths … we, in industry, need to start thinking along the lines of a Silicon Valley tech company but we can only do that if there is a credible pathway to the market, and the evaluation is at least as fast as the development,” he says.