Author: Audrey Cooper, GiveWell Philanthropy Advisor
Since our founding in 2007, GiveWell has directed over $600 million to programs that aim to prevent malaria, a mosquito-borne disease that causes severe illness and death. Malaria is preventable and curable, yet it killed over 600,000 people in 2021—mostly young children in Africa.[1]
Following the World Health Organization’s approval of the RTS,S/AS01 malaria vaccine (RTS,S) in late 2021,[2] GiveWell directed $5 million to PATH to accelerate the rollout of the vaccine in certain areas of Ghana, Kenya, and Malawi. This grant aimed to enable these communities to gain access to the vaccine about a year earlier than they otherwise would, protecting hundreds of thousands of children from malaria.[3]
Although we’re very excited about the potential of the RTS,S malaria vaccine to save lives, it isn’t a panacea. We still plan to support a range of malaria control interventions, including vaccines, nets, and antimalarial medicine.
In this post, we will:
Explain how we found the opportunity to fund the malaria vaccine
Discuss why we funded this grant
Share our plan for malaria funding moving forward
Identifying a gap in vaccine access
In October 2021, we shared our initial thoughts on the approval of the RTS,S malaria vaccine by the World Health Organization (WHO). At that point, we weren’t sure whether the vaccine would be cost-effective and were not aware of any opportunities for private donors to support the expansion of vaccine access.
In the following months, our conversations with PATH, a large global health nonprofit that we’ve previously funded, revealed that there might be an opportunity to help deploy the vaccine more quickly in certain regions. PATH had been supporting the delivery of the vaccine in Ghana, Kenya, and Malawi as part of the WHO-led pilot—the Malaria Vaccine Implementation Program (MVIP)—since the pilot began in 2019.[4] In order to generate evidence about the effectiveness of the vaccine, randomly selected areas in each country received the vaccine during the early years of the pilot, while “comparison areas” would receive the vaccine at a later date, if the vaccine was recommended by the WHO.[5]
Once the vaccine had received approval from the WHO, the WHO and PATH believed there was an opportunity to build on the momentum and groundwork of the pilot to roll out the vaccine to the comparison areas as soon as possible. However, the expectation at the time was that expanding use to the comparison areas would need to wait for the standard process through which low-income countries apply for support to access vaccines from Gavi, the Vaccine Alliance.[6] This process would have made it possible to introduce the vaccine at the end of 2023 at the earliest.[7]
However, there was another path through which these vaccines could be provided more quickly. GlaxoSmithKline (GSK), the vaccine manufacturer, had committed to donate up to 10 million vaccine doses as part of its support for the MVIP.[8] This quantity of vaccine was set aside to allow completion of the pilot program, including vaccination in the comparison areas.[9] However, additional support was needed to be able to utilize these vaccines in advance of Gavi financing, including (for example) funding to cover the costs of safe injection supplies and vaccine shipping and handling, as well as the technical assistance required to support vaccine implementation.
With funding from GiveWell, PATH believed it could provide the necessary technical assistance to the ministries of health in Ghana, Kenya, and Malawi to support them in using the donated vaccines from GSK and expand vaccine access to the comparison areas at the end of 2022—providing an estimated additional year of protection for communities at risk of malaria.[10] PATH planned to work with Gavi, UNICEF, and the WHO to ensure that the vaccine doses and other supplies could be provided to countries, as well as to assist with developing vaccine policies, training healthcare workers, raising public awareness of the program, and supporting the vaccine rollout.[11]
Making and monitoring the grant
In order to assess the opportunity, we developed a preliminary cost-effectiveness analysis and spoke to stakeholders at the WHO, PATH, Gavi, and members of the Ministries of Health in Ghana and Kenya to learn more. We estimated that this grant would enable the vaccination of over 450,000 children who wouldn’t otherwise have been vaccinated, saving over 400 lives. We published more details on the case for the grant, as well as our uncertainties, here.
Since then, we’ve kept in touch with PATH to monitor the progress of the rollout. During 2022, the Ministries of Health in each country formally approved the use of the malaria vaccine in their countries and developed plans for the rollout, including training for healthcare workers and supply chain plans. As of March 2023, implementation in the comparison areas of the pilot had begun in all three countries.
In the coming year, we hope to learn more about how many children are being treated, as well as the future costs of the vaccine at scale, which we have significant remaining uncertainties about. Additionally, implementation in the comparison areas had begun in all three countries by March 2023, which is later than our initial forecast that implementation would begin by January 2023.[12] These factors are key inputs in our cost-effectiveness analysis, so learning more will help us determine whether this opportunity was ultimately cost-effective, and improve our future funding decisions.
What’s next for GiveWell’s malaria funding
This grant aimed to provide initial access to the malaria vaccine in the comparison areas of the pilot program; as such, it’s a one-time opportunity that we don’t expect to fund again.
We will continue to monitor new developments with the malaria vaccines and may consider other grants related to RTS,S or other vaccines if we believe they are cost-effective. The WHO has published guidance recommending the use of RTS,S in certain contexts as part of a mix of interventions, which might include malaria nets and seasonal malaria chemoprevention (SMC)[13]—interventions provided through two of the top charity programs we currently recommend. However, we still have more to learn about the cost-effectiveness and implications of delivering RTS,S alongside other interventions. To help generate more evidence in this area, we recently recommended a grant of approximately $1.6 million to support a trial of the effects of perennial malaria chemoprevention delivered alongside the RTS,S malaria vaccine, which will be compared to the effects of the vaccine on its own.[14] We plan to publish more about this grant soon.
We’re also closely following the development of the R21 vaccine. Though R21 is still in late-stage trials, an earlier study showed up to 77% efficacy at protecting against malaria, higher than what’s been found for RTS,S. R21 is also reportedly less complex to manufacture than RTS,S.[15] If so, it could help alleviate expected supply constraints as the demand for malaria vaccines exceeds available doses.[16]
However, in the study linked above, the vaccine was given before the peak malaria season, in an area with seasonal (as opposed to year-round) malaria transmission. A preliminary analysis from unpublished results of a late-stage trial suggests that R21′s efficacy might be similar in areas with perennial malaria transmission, but more complete data would help us make a better-informed judgment about this. Additionally, unlike RTS,S, R21 has not yet been approved by the WHO.
GiveWell has grown to be a major supporter of malaria programs because we believe these interventions are among the best ways to save and improve lives in the lowest-income communities in the world. We’re excited to continue to invest in a range of malaria control interventions, including vaccines, nets, and SMC, as well as to investigate other potentially promising malaria programs. In particular, nets and SMC—the programs provided by our top charities Against Malaria Foundation and Malaria Consortium, respectively—are some of the most cost-effective ways we’re aware of to save and improve lives. These programs continue to offer a strong opportunity for donors to make a difference through their giving, and we remain excited to support their important work.
Notes
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“The estimated deaths in 2021 were 619 000, a slight decline compared with 2020.” World Health Organization, World malaria report 2022, p. 17
“The WHO African Region continues to carry a disproportionately high share of the global malaria burden. In 2021 the Region was home to about 95% of all malaria cases and 96% of deaths. Children under 5 years of age accounted for about 80% of all malaria deaths in the Region.” World Health Organization, “Malaria,” 2023
“Malaria is a life-threatening disease spread to humans by some types of mosquitoes. It is mostly found in tropical countries. It is preventable and curable.” World Health Organization, “Malaria,” 2023
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“In October 2021, on the advice of two WHO global advisory bodies, one for immunization and the other for malaria, the Organization made this recommendation. WHO recommends the RTS,S/AS01 malaria vaccine be used for the prevention of P. falciparum malaria in children living in regions with moderate to high transmission as defined by WHO.” World Health Organization, “Q&A on RTS,S malaria vaccine,” 2023.
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See our estimates of the numbers of children treated in our cost-effectiveness model for this grant here.
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“Vaccinations began in the 3 pilot countries in 2019: in Malawi on 23 April, in Ghana on 30 April, and in Kenya on 13 September.” World Health Organization, “Malaria: The malaria vaccine implementation programme (MVIP),” 2020
“WHO is working with PATH and GSK on the vaccine pilot programme through a collaboration agreement. PATH provides technical and project management support and is leading studies on health care utilization and the economics of vaccine implementation.” World Health Organization, “Malaria: The malaria vaccine implementation programme (MVIP),” 2020
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“It is important at this stage to learn how best to introduce the malaria vaccine into routine immunization systems, and to evaluate that introduction. To do this, some districts/sub-counties within the selected areas will have the opportunity to introduce the vaccine into their immunization schedules at the start of the programme, while other districts will not receive the vaccine until a later date, should there be a WHO recommendation for wider use. Assignment of areas into those that receive the vaccine and those that do not has been through a process called “randomization”, based on chance using a computer programme. Introducing the vaccine into some areas, while delaying it in others, is also important for understanding the public health usefulness of the vaccine and will provide key information on whether the vaccine should be introduced throughout the pilot countries and more broadly across Africa.” World Health Organization, “Malaria: The malaria vaccine implementation programme (MVIP),” 2020
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Gavi, the Vaccine Alliance is a public–private global health partnership that provides support to increase access to immunization in poor countries.
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“If GiveWell didn’t fund this opportunity, the most likely scenario is that access to these vaccines would be available only through the standard process of these countries applying for support through Gavi’s malaria vaccination program. The earliest rollout through Gavi processes would be by the end of 2023.” GiveWell’s non-verbatim summary of a conversation with PATH and WHO, January 5, 2022
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“GSK is donating up to 10 million doses of RTS,S vaccine for use in the pilot and is leading additional studies to continue monitoring the vaccine’s safety and effectiveness in routine use.” World Health Organization, “Malaria: The malaria vaccine implementation programme (MVIP),” 2020
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“The limited potential alternative use of donated doses if they weren’t used to expand vaccine access within the pilot comparison areas. As part of the Malaria Vaccine Implementation Programme (MVIP), there was an agreement that GSK would provide up to 10 million doses. It is generally understood that these doses should be used for the pilot comparison areas.” GiveWell’s non-verbatim summary of a conversation with PATH and WHO, January 5, 2022
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“If GiveWell didn’t fund this opportunity, the most likely scenario is that access to these vaccines would be available only through the standard process of these countries applying for support through Gavi’s malaria vaccination program. The earliest rollout through Gavi processes would be by the end of 2023. With GiveWell funding, the expansion to pilot comparison areas could be in the third or fourth quarter of 2022.” GiveWell’s non-verbatim summary of a conversation with PATH and WHO, January 5, 2022
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Technical assistance is a broad category, but generally refers to programs that focus on helping governments implement an intervention, rather than programs that implement an intervention directly. See expected grant activities here.
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Malawi began expanded implementation in November 2022, Ghana in February 2023, and Kenya in March 2023. Sally Ethelston, Director, Resource Mobilization and Outreach, Malaria Vaccines, PATH, emails to GiveWell, February 23, 2023, and March 7, 2023 (unpublished)
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“WHO advises countries to use a tailored mix of recommended malaria control interventions – including the malaria vaccine – to increase impact in reducing malaria illness and deaths among children living in areas of moderate to high malaria transmission.” World Health Organization, “Q&A on RTS,S malaria vaccine,” 2023.
“For malaria, WHO has recommended a range of interventions—namely, vector control, chemoprevention, diagnostic testing and treatment—to reduce transmission and prevent morbidity and mortality.” World Health Organization, “Guidelines for Malaria − 14 March 2023″
“Malaria vector control interventions recommended for large-scale deployment are: i) ITNs [insecticide-treated nets] that are prequalified by WHO, which in many settings continue to be pyrethroid-only long-lasting insecticidal nets (LLINs)” World Health Organization, “Guidelines for Malaria − 14 March 2023″
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Thus the study’s findings will only apply to perennial transmission environments.
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“An important advantage of R21/MM relates to its potential for large-scale manufacturing, which will be critical for the supply of hundreds of millions of doses of vaccine required annually for each birth cohort of children in malaria endemic regions of Africa…. The saponin adjuvant, MM, lacks the monophosphoryl lipid A adjuvant component, which is found in other adjuvants and is less complex to manufacture, and this enables large-scale and low-cost supply of R21/MM.” Datoo et al. 2021
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“The malaria vaccine market faces considerable supply constraints in the short term and potentially into the medium term, with initial supply expected to fall substantially short of demand.” Gavi, the Vaccine Alliance, Market Shaping Roadmap: Malaria Vaccines, p. 2
Thanks for this update this makes a lot of sense. The cost-effectiveness of a malaria vaccine could well rival and even exceed nets, especially if this RTS’S vaccines real-world effectiveness comes close to the incredible effectiveness shown in the initial trial.
My only query around vaccines is how neglected they really in terms of funding. GAVI, UNICEF and the WHOa s as mentioned are obviously huge players but also direct government aid and even the Gates foundation have helped to fund malaria vaccine trials and rollouts.
It surprises me a little that a high profile malaria vaccine like this wouldn’t get all the funding it needed without GiveWell input, but I trust GiveWell have considered that well.
One other issue I have is that I think it is possible like Kenya, Ghana and Ugandan governments have enough capacity now to be able to deliver these vaccine programs with their own systems without 5 million dollars in help from an NGO like PATH. That’s a LOT of money for logistic support. Having another NGO in between GAVI / vaccine producers and a government which is accustomed to rolling out vaccines seems inefficient. I’m not sure how much “technical assistance” they need. Here in Uganda vaccine rollouts no longer involve a huge amount of NGO input, with Polio and other vaccines often rolled out at fairly short notice without too much trouble. The bottlenecks that I see seem only to be paying extra allowances to those in the vaccine supply chain and those giving the vaccines. Obviously I might be missing something about the logistics specifically of difficulties in distributing the vaccine.
To put it more simply, if the government of Kenya was given just the vaccine and $500,000 (or less) would they have been able to do a similar job without help from PATH?
As another idea is that perhaps a trial could have been done where PATH were put in charge of the rollout in one country (Ghana), and only the Government in another (e.g. Kenya) to assess just how much PATH really improved efficiency.
Nice work Givewell as usual!
Hi, Nick,
Thanks for your comment! Apologies that it took a while to respond to this.
Re: how much funding is needed to successfully roll out the vaccine, we’ve provided a budget breakdown on the grant page. The majority of this funding is going toward training and other activities needed to distribute the vaccine, vaccine-related supplies, and shipping and handling for the doses donated by GSK. Only about $1.8 million of the total, or less than half, is going toward the costs of having PATH and WHO provide technical support for this project.
For every grant opportunity we evaluate, we do consider the likelihood that another funder will step in to cover the costs absent our support. In a conversation with PATH and WHO, we learned that there were no other suitable candidates for funding this rollout of RTS,S to comparator areas, though we didn’t independently verify this.
As for whether the governments of Kenya, Ghana, and Malawi could successfully speed up the implementation of RTS,S without NGO/WHO technical support, this is a subjective assessment. We frequently hear from NGOs that the governments where programs we fund operate tend to have many competing priorities, so progress on projects like this can be slow. The theory is that providing dedicated funding (and with it, human capacity) for a single project can accelerate the timeline of results. We try to confirm whether this is right by talking to other relevant actors, including government officials themselves.
It would be interesting to try out what you suggest—giving the funding directly to a country government to see if they could achieve the same results without technical assistance—but because there are so many country-specific factors that inform the success of an intervention, we think it’d be hard to tell if a slower vaccine rollout in a given country was due to lack of technical assistance or some other factor.
I hope that’s helpful!
Best,
Miranda Kaplan
GiveWell Communications Associate
Thanks for this. Any thoughts or comments on the prospects of the new R21/Matrix-M malaria vaccine?
Hi, Peter! So sorry I missed this question earlier and have been delayed in responding.
We’ve described in the above post what we know about R21 so far (see the second and third paragraphs from the end). To summarize, R21 has been shown to have high efficacy in protecting against malaria, but it’s unclear to us so far how generalizable those results will be. R21 is also reportedly less complicated to manufacture, which could be helpful as demand for malaria vaccine is expected to outstrip supply—but we can’t independently verify this. We’ll keep monitoring the literature on R21, and we’ll consider any funding opportunities as they come up.
Best,
Miranda Kaplan
GiveWell Communications Associate