Summary
A new type of net called a PBO net is being trialed that could prove effective in killing those mosquitoes that are showing resistance to the insecticide used on standard nets.
PBO, piperonyl butoxide, is a chemical synergist that is safe for humans that is added to the net and works by ‘switching off’ the mosquitoes’ insecticide resistance mechanism allowing the insecticide on the net to do its job – cause ‘knock down’ – i.e. kill the malaria-carrying mosquitoes.
AMF funded six million PBO nets that were distributed in Uganda between March 2017 and March 2018 to protect 10.8 million people and an 18-month randomized controlled trial (RCT), a gold-standard study, to help answer the following question:
Are PBO nets more effective at preventing malaria in areas where some mosquitoes have developed resistance to the insecticide used on LLINs and, if so, how much more effective and under what conditions?
Work has been proceeding well, on time and on budget with the results planned for publication in Spring 2019.
Full detail
The current situation
Malaria is decreasing globally. In the last 15 years, malaria deaths and cases have fallen by 60% with long-lasting insecticide-treated nets credited in studies for being responsible for 70% of this decline.
However, there are currently two significant challenges to achieving further reductions in malaria. First, there is not enough funding to ensure basic malaria control activities take place in all malaria-affected countries. Second, some mosquitoes are showing resistance to the insecticide that is used on long-lasting insecticide-treated nets (LLINs).
Darwin showed how species adapt to their environment and that is what some populations of mosquitoes are doing. It is not surprising, therefore, that some mosquitoes are showing insecticide resistance.
Although only a small proportion of all mosquitoes, estimated at <2%, show this resistance, we must act now to ensure the population of resistant mosquitoes does not spread and existing resistance levels are reversed.
Although LLINs can still be effective in acting as a physical barrier to prevent a malaria-carrying mosquito reaching a person sleeping underneath the net, we do not want to lose the very important element in malaria control - the ‘knock down’ (killing) of mosquitoes that occurs when they land on and walk on a net and pick up insecticide via their feet.
Defeating insecticide resistance: PBO Nets
A major tool in defeating insecticide resistance could be the PBO net. This is a standard LLIN that has a chemical ‘synergist’ called piperonyl butoxide (PBO) added to it. PBO, which is safe for humans, works by switching off the mosquitoes’ insecticide resistance mechanism leaving the net to have its normal knock down effect.
In recent years, the results from laboratory and small-scale hut trials indicated that the PBO net could be highly effective against insecticide resistant mosquitoes. There was widespread agreement in the scientific community that the PBO nets needed to be tried at scale. As PBO nets provide protection that is at least as good as that from standard LLINs, there is no ethical issue when considering the distribution of PBO nets at scale.
AMF agreed to back this view and funded 6 million PBO nets that were distributed in Uganda between March 2017 and March 2018, including in areas where levels of insecticide resistance had been recorded. All of these nets were funded by AMF donors to whom we had made the promise that 100% of their donations would fund nets. Two different types of PBO nets were funded from two different manufacturers.
Assessing the effectiveness of PBO nets
As this was the first time PBOs had been deployed at scale, AMF also funded a rigorous academic study to test their effectiveness compared to standard (‘non-PBO’) LLINs. Funding for the study was provided only by donors who were comfortable funding research.
The study has a clear aim to answer the following question:
Are PBO nets more effective at preventing malaria in areas where some mosquitoes have developed resistance to the insecticide used on the nets and if so, how much more effective and under what conditions?
The AMF-funded study is being led by the Liverpool School of Tropical Medicine (LSTM) who are working closely with the London School of Hygiene and Tropical Medicine (LSHTM), University of California San Francisco (UCSF) and researchers at the Infectious Diseases Research Collaboration (IDRC) in Kampala and at Makerere University, both of the latter in Uganda.
The study has been designed to provide results that are statistically significant. This has been achieved by having many study sites, 124 ‘clusters’, so that the study has statistical ‘power’, and by ensuring that clusters can be compared with the only relevant difference between them being whether they received standard LLINs or PBO nets. In this way, any differences in outcome can be linked to the net type.
The primary indicator being monitored in the study is malaria prevalence in children and this is being done using highly accurate testing methodologies. The effect of PBO nets on the mosquito population is also being studied. The study team carried out tests and collected data before nets were distributed, a baseline study, and has collected data in two further stages, at 6 months and 12 months post-distribution of the nets.
Work has been proceeding well, on time and on budget with the results planned for publication in Spring 2019. Another organisation has agreed to fund data collection at 18-months and a further study at 24-months may occur.
It is important to us that the study be open to all. During the planning and consultative phase, AMF shared widely the study protocol and received valuable input. All results will be published in full.
By understanding to what extent PBO nets can play a role in combatting insecticide resistance in mosquitoes, the ultimate value of this study is to help net funders, including health ministries, make informed decisions about the nets they purchase and distribute that will optimize malaria control.
Of note, a recent trial in Tanzania has reported positive results from a smaller scale deployment of PBO nets: malaria prevalence was less in areas using PBO nets than in control areas using standard nets. At 9 months after nets were distributed, malaria prevalence was 531 out of the 1,852 children tested (29%) compared to 767/1,809 (42%) in the control area; at 21 months 865/1,930 (45%) compared to 1,255/2,034 (62%). These are significant improvements.
We will keep our supporters up to date both with the results of the study and as we continue to explore innovations in the fight against malaria.