Supporters of the Against Malaria Foundation in recent years may have had even more impact than they expected.

The Against Malaria Foundation (AMF) is a GiveWell top charity because we believe its program to distribute insecticide-treated nets prevents people from dying of malaria. AMF-supported net distributions are incredibly cost-effective; we estimate that a $2,000-3,000 donation averts one death.[1] AMF’s work is important in and of itself to fund.

Not all AMF donations, however, just support typical net distributions. In recent years, AMF supported research on a new type of insecticide-treated net, the piperonyl butoxide (PBO) net. This research itself (i.e., researcher time, equipment, and administrative costs) was funded by a small number of AMF donors who explicitly agreed to support it. The research was conducted on nets that were contributed by a broad group of AMF donors.

Preliminary data suggest that PBO nets are more effective at preventing malaria than standard insecticide-treated nets in areas where mosquitoes have developed insecticide resistance. We think it is likely that AMF sped up the completion of a large-scale, high-quality study of these new nets.

We’re thrilled to recommend charities that contribute research in the fields in which they operate. AMF doesn’t just prevent deaths from malaria by distributing nets—it has improved our and others’ understanding of which nets can work best in the future. This post is to share this story with our donors, whose contributions make this work possible.

Summary

In this post, we’ll discuss:

• Insecticide resistance and the potential of PBO nets. (More)
• AMF’s role in PBO net research. (More)

What is insecticide resistance? How could PBO nets help?

AMF distributes insecticide-treated nets to prevent malaria. These nets, which are typically hung over sleeping spaces, block mosquitoes from biting. They’re also treated with insecticide to repel and kill mosquitoes.[2] There is strong evidence that insecticide-treated nets prevent malaria.

Mosquitoes’ resistance to standard insecticide seems to be rising.[3] We estimate (very roughly) that insecticide-treated nets are one-third less effective in the places where AMF works than they would be in the absence of resistance. (Even with this adjustment, we continue to estimate that AMF’s work is highly cost-effective.)[4] It has been challenging to estimate the precise degree to which insecticide resistance is reducing nets’ effectiveness due to a lack of high-quality evidence.[5]

A new type of net offers a promising countermeasure as well as some insight into the level of resistance. Piperonyl butoxide (PBO) nets contain the standard insecticide as well as PBO, which inhibits the enzymes in mosquitoes that enable insecticide resistance.[6] The World Health Organization (WHO) approved a small rollout of PBO nets in 2015. However, at the time, limited information was available on their performance relative to standard nets and the WHO did not recommend them universally over standard nets.[7]

The first randomized controlled trial (RCT) of PBO nets was conducted in Tanzania from 2014 to 2016 (Protopopoff et al. 2018).[8] The WHO conditionally recommended PBO nets in 2017 based on the Protopopoff findings. It said it needed to see results from another study before recommending that PBO nets be used in additional contexts.[9]

AMF’s role in PBO net research

AMF enabled another RCT of PBO nets by seeking research collaborators, serving as the primary funder of the research, and funding the nets in the study.

Although it is difficult to prove, it appears that AMF contributed to a second PBO RCT occurring earlier than it otherwise would have and at a larger scale.[10] If PBO nets are more effective than standard nets, rolling them out sooner and more broadly could avert many more deaths from malaria.

AMF told us that it was interested in funding research on PBO nets in 2015.[11] After supporting a small-scale initial study of PBO nets in the Democratic Republic of the Congo in 2016, AMF made a more significant investment as the primary funder of a large-scale RCT in conjunction with a planned 2017-18 national net distribution campaign in Uganda.[12]

In addition to supporting the study financially, AMF identified researchers to lead the study and managed procurement of the four different types of nets that were compared (two PBO nets and two standard nets). The national campaign by the Uganda Ministry of Health included millions of nets funded by AMF.[13] AMF also supported the first two follow-ups to the study, assessing the impact on malaria six and twelve months following the campaign.[14]

AMF’s participation seems to have sped up the pace of research on these nets. We think most researchers in this space would agree the Uganda study is the second major PBO RCT.[15] We are not aware of another RCT being conducted on PBO nets, nor have we heard of other actors offering to do this research. It is difficult to know by how much AMF may have sped up PBO research, but it seems likely that it did.

Our impression is that the number of people participating in AMF’s study is unusually large relative to typical RCTs of global health interventions. The Uganda RCT involved 10.2 million nets.[16] By contrast, the earlier Protopopoff study in Tanzania involved 90,000 nets.[17]

Finally, based on the study design, the Uganda RCT appears to be high quality.

The large scale and quality design suggest the results of this study will significantly update the field on the effectiveness of PBO nets and the degree to which insecticide resistance is reducing the effectiveness of standard nets. Other funders seem to agree on its promise. The U.K. Department for International Development and Gates Foundation each funded additional follow-ups to the study, tracking the impact of the PBO nets at 18- and 24-months post-distribution.[18]

The Uganda RCT could influence a large amount of government and philanthropic funding for malaria programs. We estimate that $2.1 billion was committed to nets globally between 2018 and 2020.[19] If PBO nets turn out to be more effective than standard nets and AMF contributed to speeding up this high-quality study, it could improve the effectiveness of a large amount of malaria prevention funding.

Conclusion

AMF shared preliminary findings from the Uganda study in November.[20] They’re promising. AMF reported that PBO nets were more effective at reducing malaria cases than standard nets six months after distribution (26% more), 12 months after distribution (27% more), and 18 months after distribution (16% more).[21] There will be one more measurement completed as part of this study.[22]

The full results from the Uganda RCT have not been published. We will review them closely and share our conclusions once they are available.

Our current best guess is that in many of the locations where AMF works, PBO nets are more cost-effective than standard nets. We estimate that in areas with sufficiently high insecticide resistance, the benefits of PBO nets outweigh the higher cost of these nets. We expect to revise our estimate of the cost-effectiveness of PBO nets once we have fully reviewed the results from the Uganda RCT. We look forward to seeing how the research community interprets these results and whether they conclude that PBO nets are a worthwhile investment. A possible sign of increased demand for PBO nets is that one manufacturer of PBO nets increased its production by a large amount in 2020, according to AMF.[23]

AMF’s work on PBO nets is one example of how our top charities can have more impact than expected. We’re thrilled to recommend our top charities based on the great work they do: not only on direct delivery of cost-effective programs, but also on new research to shape their fields of work.