Note: This page summarizes the rationale behind a GiveWell grant to the Liverpool School of Tropical Medicine (LSTM). LSTM staff reviewed this page prior to publication.
Published: October 2025
Summary
In August 2025, we made a $69,050 grant to the Liverpool School of Tropical Medicine to collect data that will inform the design of a potential randomized control trial (RCT) in Malawi. The RCT would look at the effectiveness of different combinations of chemoprevention drugs outside of the Sahel. This grant will fund researchers to collect data on malaria hospitalizations including severe cases from the past four years in five hospitals in potential study sites. This data may inform the location and sample size of the potential RCT. The data collection will be led by Lauren Cohee at the Liverpool School of Tropical Medicine and Donnie Mategula at the Malawi-Liverpool Wellcome Programme.
Background
Malaria chemoprevention is a preventative treatment in which antimalarial medicines are given to both clear existing infections and prevent malaria cases. The two main types of chemoprevention programs we’ve looked into and funded at GiveWell are seasonal malaria chemoprevention (SMC) and perennial malaria chemoprevention (PMC).1
There are open questions about which chemoprevention drugs should be used for these programs.2 The potential RCT would get at some of these questions by using different combinations of chemoprevention drugs and assessing the effects on malaria cases and hospitalizations.
Case for the grant
This grant pays for the researchers to collect data on the baseline number of malaria hospitalizations and severe cases in potential study areas in Malawi. This data collection could inform the design of the trial in two ways:
- Sample size: Because malaria hospitalizations and severe cases are a key outcome, knowing the baseline rate would allow us to set an appropriate sample size: large enough to detect meaningful changes, but not so large that we fund an unnecessarily big sample. The current assumption in the RCT design is that 4% of the under 5 children in the trial population would be hospitalized due to malaria in the absence of SMC. If the rate were lower, it’s possible that the sample size would need to be so large that the RCT becomes prohibitively expensive. If the rate was higher, e.g., 5%, the sample size, and therefore cost, of the RCT could be reduced while staying powered to detect meaningful changes.
- Location: By collecting this data in five regions (districts), the researchers can choose the final RCT location with the highest baseline hospitalization rate. The sample size can therefore be sized appropriately and potentially lead to lower costs for an equivalently-powered trial. The researchers will also participate in site engagement meetings to make sure hospitals are aware of and willing to participate in a potential trial.
Overall we think this is a relatively small investment that will inform the design and grant decision for a much larger potential RCT, currently projected to cost $6m.
Reservations
We have two reservations:
- Our main reservation is that we may not fund the potential RCT for reasons unrelated to the data collected through this grant. For example, we might decide this trial is relatively unlikely to influence policy, based on discussions we plan on having with other funders of malaria programs and the World Health Organization.
- The scoping grant could produce misleading results and lead to bad funding decisions. In the RCT, clinicians stationed at the hospitals would collect data in real time, but data collection for this grant relies on hospital records from the past four years. If those records are incomplete, we could underestimate the true hospitalization rate. That would mandate a larger sample size than necessary, potentially spending excess money on the trial or wrongly deciding it’s too expensive to run. The researchers plan to check the hospital data against national death registry records, which we believe reduces this risk.
Forecasts
| Confidence | Prediction | By time | Resolution |
|---|---|---|---|
| 40% | Based on this data collection, we estimate a 4% baseline hospitalization rate among children not receiving SMC during the high transmission season in Malawi. | September 2025 | |
| 30% | Based on this data collection, we estimate a 3% baseline hospitalization rate among children not receiving SMC during the high transmission season in Malawi. | September 2025 | |
| 30% | Based on this data collection, we estimate a 5% baseline hospitalization rate among children not receiving SMC during the high transmission season in Malawi. | September 2025 | |
Sources
| Document | Source |
|---|---|
| Laufer et al. 2006 | Source |
| Roux et al. 2021 | Source |
| WHO, Guidelines for Malaria, 2022 | Source (archive) |
- 1
SMC is given to under-5 children monthly during the peak season of malaria transmission, while PMC is given to children under 2 at predefined intervals based on child age.
We’ve allocated over $500 million to Malaria Consortium’s SMC program, which is one of our Top Charities, and have funded a pilot of PMC in the Democratic Republic of the Congo. - 2
Open questions the potential RCT would aim to help resolve are:
- Is sulfadoxine-pyrimethamine + amodioquine (SPAQ), the drug combination used in SMC, as effective for malaria chemoprevention outside the Sahel vs. inside the Sahel region of Africa?
- Outside of the Sahel, more malaria parasites have genetic markers associated with resistance to SP, one of the main ingredients of SPAQ. When SMC was first recommended by the World Health Organization is 2012, the recommendation was confined to areas with low prevalence of SP resistance markers
- In 2022, the World Health Organization expanded its SMC recommendation to support implementation outside the Sahel, where SP resistance markers are more prevalent. Two trials conducted in Mozambique and Uganda suggest that SMC with SPAQ could still be highly effective in these settings, but more evidence is needed.
- Does SP contribute a separate antimalarial effect?
- We’ve seen (unpublished) evidence from Uganda that suggests most of the antimalarial effect is being driven by amodiaquine. If that’s the case, that would undermine the anti-resistance benefits of combinational drug therapy. We think this evidence is more suggestive than conclusive, as the trial wasn’t designed to disentangle the separate antimalarial effects of both drugs.
- How effective is chloroquine for chemoprevention?
- Chloroquine was the predominant front-line treatment for malaria in Sub-Saharan Africa for decades, up until growing drug resistance began to nullify its effectiveness in the late 1970s (see Roux et al. 2021 for a more detailed history). Now that resistance appears to have waned, we think chloroquine could be a useful back-up drug for chemoprevention. The drug has already been tested as chemoprevention in pregnant women and school-age children, but not in the under-5 population.
- Is sulfadoxine-pyrimethamine + amodioquine (SPAQ), the drug combination used in SMC, as effective for malaria chemoprevention outside the Sahel vs. inside the Sahel region of Africa?