Malaria Consortium — SMC Renewal in South Sudan (October 2024)

Note: This page summarizes the rationale behind a GiveWell grant to Malaria Consortium. Malaria Consortium staff reviewed this page prior to publication.

Published: December 2024

The organization and intervention

Malaria Consortium's seasonal malaria chemoprevention program (SMC) has been a GiveWell top charity since 2016. SMC, the focus of this grant, is a public health strategy that involves administering antimalarial drugs to children aged 3-59 months during peak malaria transmission seasons. GiveWell has supported Malaria Consortium's SMC programs in several countries across the Sahel region of Africa, consistently finding them to be highly cost-effective interventions for reducing childhood mortality and morbidity from malaria.
Malaria Consortium has demonstrated strong capabilities in implementing SMC programs, consistently achieving high coverage rates1 and maintaining robust monitoring and evaluation practices.2 We believe their experience in operating in South Sudan3 makes them well-suited to continue and potentially expand their work in the country.

What we think this grant will do

Malaria Consortium has supported SMC in South Sudan since 2022. The program began as a small-scale implementation pilot and scaled to two counties of Northern Bahr el Ghazal State (including one refugee camp) in 2023.4 This grant of ~$1.1 million will enable Malaria Consortium to continue delivering SMC to children in these two counties during the 2025 SMC season.

We think this grant will cause children to receive SMC who would not otherwise have received it, which in turn will reduce under-5 malaria cases and deaths. We also think this grant will maintain the stability of Malaria Consortium's operational capacity in South Sudan (e.g., retaining local staff) while we scope the potential for two other grants in the country that would likely require at least some of this capacity (see details below).

• 45% staff costs
• 19% intervention delivery costs
• 19% Malaria Consortium operational costs
• 11% management fee
• 6% digital, research, and external relations costs
• 1% medicines, other commodities & freight6

The case for the grant

We model the cost-effectiveness of Malaria Consortium's SMC program in South Sudan at ~7x cash, which is below our bar. However, we believe that supporting one additional year of SMC in South Sudan could provide significant option value for other potentially cost-effective grants we'd like to investigate by retaining Malaria Consortium presence in the area (staff costs represent nearly half of the grant costs—see above). Additionally, our impression is that our cost-effectiveness estimates of SMC could be biased downward due to underestimated malaria burden, though we remain uncertain about this and aim to improve our model as part of this grant (see more below).

Option value for additional cost-effective grantmaking in South Sudan

This grant is, in part, a means of retaining Malaria Consortium's operational presence in South Sudan, as we investigate the potential to support two additional projects in the country that we think could be highly cost-effective:

• Vaccination program coadministered with other health interventions – Our initial modeling suggests South Sudan could be one of the most cost-effective locations in which to implement a program that incentivizes or provides childhood vaccinations due to the combination of a high rate of child mortality from vaccine-preventable diseases and relatively low baseline vaccination coverage.7 We'd previously discussed with Malaria Consortium the possibility of using its SMC platform in South Sudan as a base on which to layer vaccinations and other health interventions.8 However, we now expect there are limited cost savings and potential implementation challenges with using SMC as the base layer for a bundled intervention package (e.g., misalignment between the vaccine schedule and SMC campaign timing). Instead, we are interested in a pilot testing the effectiveness of a layered health program using vaccinations as a base layer.

Our understanding is that maintaining Malaria Consortium's SMC program for an additional year would still be valuable for our investigation into a vaccination-centered health program because:

• Some staff at the senior level, and possibly at the field level, would be carried over,9 and continuing to fund these staff (instead of having to temporarily lay them off) would be less disruptive
• It is still possible we end up finding that SMC is a valuable component of the bundled health package, in which case it would be less disruptive to program beneficiaries and campaign staff for the SMC program to remain funded through next year
• The SMC campaign could provide a strong platform for conducting household surveys on coverage of various health interventions, which could inform design of the pilot program10

• Research to improve data on malaria burden – The largest uncertainty we have in our cost-effectiveness model for SMC in South Sudan is the accuracy of the malaria burden data we are using (see more below). We have discussed the possibility of Malaria Consortium and its research partners conducting a data collection and/or modeling exercise to generate more accurate estimates of malaria mortality and incidence. We expect that continuing to support Malaria Consortium's SMC program next year would help ensure local staff capacity is available to engage in this project.

Availability of existing SPAQ stock

Our understanding from Malaria Consortium is that the SMC drugs it procured for implementation in its 2024 campaign in South Sudan will not be used due to a drug donation from UNICEF. This means that there will be existing drug stock already available to support SMC implementation in 2025, reducing grant costs by ~$0.2 million. Our best guess based on correspondence with Malaria Consortium is also that these medicines are a sunk cost and are unlikely to be used if we do not support Malaria Consortium's SMC program in 2025.11

Reservations and Uncertainties

We may not ultimately fund the other projects

The vaccination-centered multilayered health program we are investigating would be the first of its kind that we've supported, and though the idea seems promising, it remains speculative and untested. There are a number of ways in which this could fail to materialize into a cost-effective program, including:

• The actual implementation costs could be significantly higher than in our current model (which assumes the same costs as New Incentives' conditional cash transfer (CCT) program in Nigeria). Our impression that South Sudan has less infrastructure, and would have reduced economies of scale, compared with where New Incentives works. A program could still be above our cost-effectiveness bar if it uses a different, more efficient approach than CCTs, or if it has a greater impact than CCTs – both of which we think are plausible but which may require trial and error.
• New data collection could indicate relatively high baseline coverage of vaccination and other health services.
• Interventions to provide or increase uptake of health services like vaccinations may not be very successful in the targeted region.

The malaria burden research we are investigating would be valuable largely for helping us better allocate our available funding to programs in the most cost-effective geographies. We do not currently have plans to direct major amounts of funding to malaria programs in South Sudan, and our best guess is that new research would not cause us to significantly change our funding allocation. Moreover, it seems possible that data collection and/or modeling burden in a humanitarian context like South Sudan is sufficiently difficult, such that we ultimately may not put much weight on the results of this research.

Cost-effectiveness of SMC in South Sudan

We currently model cost-effectiveness of SMC in South Sudan at ~7x cash, though our confidence intervals in this estimate are wide relative to other SMC programs that we support. The two most important factors in our model are malaria burden and cost per SMC cycle:

• Malaria burden– Our current best guess of the annual malaria mortality rate among children who do not receive SMC in the areas where Malaria Consortium's program operates is 0.47%, based on nationally representative data from the Institute for Health Metrics and Evaluation’s (IHME) most recent Global Burden of Disease (GBD) model.12 However, there are several reasons we think this could be a significant underestimate or overestimate (our 25th and 75th percentile confidence interval for this parameter implies cost-effectiveness of 2x-11x):
  • Subnational data from the Malaria Atlas Project imply lower burden – We also conducted an analysis of Malaria Atlas Project (MAP) subnational mortality data specific to Northern Bahr El Ghazal state (where Malaria Consortium's program operates), which suggests a ~50% lower annual malaria mortality burden.13 However, we have low confidence in this subnational mortality data for the following reasons:
    • Our understanding is that MAP is geospatially smoothing burden data,14 which in this case could bias estimates of malaria burden in Northern Bahr El Ghazal state downward due to the lower malaria burden estimated in bordering regions of Sudan.15
    • MAP's data implies a population estimate for Northern Bahr El Ghazal state that is ~60% lower than the census-based estimate. We are unsure what could be causing this large discrepancy, but it reduces our confidence in the accuracy of the malaria burden estimates.
  • 2017 Malaria Indicator Survey (MIS) results imply higher burden – Comparing the results of South Sudan’s 2017 MIS survey to the data that we have from the GBD project and MAP, the MIS results consistently imply a higher burden than what we currently use to estimate the effectiveness of the SMC campaign.
    • The MIS used both rapid diagnostic tests (RDTs) and microscopy to assess malaria burden.16 The MIS estimate for the malaria burden in South Sudan using RDTs is ~40% higher than the GBD estimate that we currently use (32% vs 23%). However, the MIS estimate using microscopy is ~10% lower than the same GBD estimate (21% vs 23%)
    • Moreover, MIS data for RDT-confirmed malaria prevalence in Northern Bahr El Ghazal is ~4x (53% vs 13%) higher than what MAP reports and using MIS data for microscopy-confirmed malaria prevalence is ~2.5x higher (33% vs 13%) than what MAP reports. Additionally, MIS data suggests lower rates of care-seeking in Northern Bahr El Ghazal compared to the national average.
  • Malaria Consortium suggests that burden data is poor quality and biased downward – Malaria Consortium has told us that the malaria burden in South Sudan could be much higher than what is reported in available data sources due to underreporting by health facilities and high prevalence of malaria outbreaks not captured in available data.17 We have not investigated these claims, though they seem intuitively plausible to us.
• Cost per SMC cycle administered – Our most recent estimate of cost per SMC cycle, based on actual cost and coverage data from South Sudan in 2023, indicated a cost of ~$8 per SMC cycle administered, which is 2-6 times the 2023 cost in any other country where we support Malaria Consortium's SMC program. Our forward-looking estimates of cost per SMC cycle in South Sudan (~$5 for 2025) are cheaper, but still higher than in any other country; these forward looking estimates are based on Malaria Consortium's projected budget for 2025 and an assumption that it will achieve the same average coverage rate it did in 2023. Malaria Consortium has flagged to us that it does not expect costs to decrease much further than this without expanding the program scale18 (which is currently much smaller than its scale in other countries19 ), and even with increased scale, costs are still likely to be relatively high.20 It's possible that if GiveWell were to fund expansion of the program, it would reduce cost per SMC cycle sufficiently to bring the program above our cost-effectiveness bar.

Other uncertainties in our SMC cost-effectiveness model

Our CEA for SMC in South Sudan includes a number of uncertainties beyond malaria burden and costs. Though our current best guess is that none of these parameters are major drivers of uncertainty in the cost-effectiveness in our model, they could be decision-relevant for a future renewal grant if we ultimately find that we're underestimating or overestimating several or all of these parameters. We also expect to improve our confidence in several of these parameters over the course of this grant (see our plans for follow-up).

• Proportion of malaria mortality occurring in the SMC season – Our model assumes that 70% of malaria mortality occurs during the SMC season in South Sudan. This estimate is based on recent research indicating >60% of transmission occurs in a four-month period, coupled with Malaria Consortium's plan to implement five SMC delivery cycles.21
• SMC effect size – Our model assumes that SMC reduces malaria mortality among children that receive the intervention by 79%, which is our current best guess for this parameter in countries in the Sahel region of Africa. (South Sudan is proximate to, but not technically in the Sahel.22 ) A shallow literature search suggests resistance to sulfadoxine-pyrimethamine (SP), one of the two drugs used in SMC, could be high in South Sudan, and we view drug resistance as the primary mechanism for differences in SMC effect size across geographies.23 However, a recent quasi-experimental study conducted in the location where Malaria Consortium's SMC program operates in South Sudan found very high effectiveness of SMC at reducing malaria.24 Additionally, Malaria Consortium has told us they expect SMC effect size could be higher in South Sudan than conventional estimates would indicate, due to lower access to other malaria prevention strategies.25
• Adjustment for the development of drug resistance – As mentioned above, we are uncertain to what extent drug resistance impacts current and future SMC effectiveness in South Sudan. Currently, our model assumes an adjustment for the development of drug resistance affecting future SMC impact of -4%, which is our current best guess for this parameter in countries in the Sahel region of Africa, where we believe drug resistance is lower.
• Adjustment for malaria vaccines – Our model includes an adjustment for the effect that the rollout of malaria vaccines will have on reducing malaria-attributable mortality and therefore the potential impact of SMC. We currently assume an adjustment of -14% for South Sudan. However, our model contains a number of subjective inputs, including predictions for future malaria vaccine coverage, that we are highly uncertain about.
• Adjustment for crowding out other funders – We have not deeply investigated the funding landscape for SMC in South Sudan and we continue to use our estimate of the chance our support is crowding out other funders from our 2022 model (15%). It is possible that the funding landscape has changed, though our best guess is that it is unlikely another funder would be able to mobilize resources in time to support the 2025 SMC campaign.

Simple CEA for SMC in South Sudan

A sketch of our cost-effectiveness analysis is in the table below. You can see the full cost-effectiveness analysis here.

Possibility that we could retain option value with a smaller grant

Since we view a key benefit of this grant as retaining the option value to investigate non-SMC grants in South Sudan, we could work with Malaria Consortium to determine the smallest amount of funding necessary to retain this option value. However, we believe this would not be worth our and Malaria Consortium's time given the relatively small size of the grant, the fact that about half of the cost of the grant is staff costs, and our best guess that a smaller grant would still be disruptive to Malaria Consortium's operations and staff in the region.

Additionally, we think it's plausible that we will decide to continue funding SMC in South Sudan after revisiting estimates of malaria burden and other inputs to our cost-effectiveness model.

Plans for follow up

• We will review Malaria Consortium's proposal for vaccination-centered health programming and malaria burden research in South Sudan.
• We will request that Malaria Consortium submit spending reports and coverage surveys for 2024 and 2025 SMC campaigns in South Sudan, as it has for all previously funded campaigns. Based on this reporting, we'll develop updated estimates of cost-effectiveness for Malaria Consortium's SMC program.
• We will have biannual calls with Malaria Consortium with the explicit goal of understanding how SMC implementation is progressing, including in South Sudan.
• We will investigate several open questions as part of our broader research agenda for the malaria team, including:
  • Considering all sources of information, what is our best estimate of the burden of malaria in a given area?
  • How would the cost per SMC cycle change at different sizes (i.e. number of children targeted) of the program in South Sudan?
  • What is the effect of the malaria vaccine rollout on the malaria burden averted by SMC and other interventions?
  • How prevalent is resistance to SMC drugs in South Sudan and what role is continued SMC implementation playing in increasing resistance?
  • What is our updated view of the effect size for SMC on reducing malaria, given newer evidence?
  • How seasonal is malaria prevalence and mortality across the contexts where we support SMC programs?

Internal forecasts

For this grant, we are recording the following forecasts:

Our Process

• We created an updated cost-effectiveness estimate for SMC in South Sudan, including an updated cost per SMC cycle based on Malaria Consortium's updated 2025 budget and proposal document, and our analysis of national and subnational malaria burden data.

Sources

• 1

  "Overall, we believe that results from Malaria Consortium’s coverage surveys provide relatively strong evidence that a high proportion of the target population has been reached with SMC in previous campaigns. Overall coverage (the % of target children receiving SMC) from post-round surveys has been 78% in Nigeria, 85% in Chad, 87% in Togo, and 92% in Burkina Faso." GiveWell, Malaria Consortium – Seasonal Malaria Chemoprevention, 2024

• 2

  See our review of Malaria Consortium's monitoring and evaluation practices here.

• 3

  "Malaria Consortium has been operating in South Sudan since 2005 from our office in Juba. Our work
  initially focused on long-lasting insecticidal net (LLIN) distributions and healthcare worker training for malaria prevention, treatment and control. Our portfolio has since expanded to include primary healthcare, nutrition, neglected tropical diseases and community health — with a focus on integrated community case management for malaria, pneumonia and diarrhoea." Malaria Consortium, South Sudan
  Country strategy 2021–2025, p. 2

• 4
  • "SMC was introduced in South Sudan in selected villages in one county of Northern Bahr el Ghazal state in 2022 as part of an implementation study conducted by Malaria Consortium and the National Malaria Control Programme, with a target population of 20,000. In 2023, the target population grew to 60,000 (Table 20), because SMC was expanded to all villages in the county where the study had been conducted in the previous year, as well as a second county, which had served as a control in 2022 (Figure 10). The target population also increased due to an influx of refugees and returnees as a consequence of the conflict in neighbouring Sudan. During the 2023 SMC round, approximately 500 SMC-eligible children lived in an official camp for IDPs in one of the SMC-implementing counties." Malaria Consortium, 2023 Philanthropy Report, p. 31
  • Note that our support in South Sudan was for reallocation of available funding from other SMC grants we had recommended to Malaria Consortium; we have never made an explicit funding recommendation to support this program: "In 2022, Malaria Consortium began using GiveWell-directed funding to support implementation research in two counties in South Sudan. We did not make a formal grant to support this work but in early 2022 expressed support for Malaria Consortium reallocating available funding to conduct this work, based on our initial 5.8x cash estimate of the cost-effectiveness of SMC in this region of South Sudan (Northern Bahr El Ghazal state) and the fact that our funding bar at the time was 6x cash. In late 2022, though our bar had increased to 10x cash, we again expressed support for Malaria Consortium reallocating available funding to continue delivering SMC in those two counties for two more years, through 2024." GiveWell, SMC context document, 2024 (unpublished)

• 5

  Malaria Consortium, 2025 SMC South Sudan budget with management fee

• 6
  • Note: This is a very small percentage in 2025 because Malaria Consortium will be delivering sulfadoxine-pyrimethamine + amodiaquine (SPAQ) that it procured for its 2024 campaign but which will not be used due to a SPAQ donation from UNICEF in 2024.
  • "UNICEF donated SPAQ for use in the 2024 SMC round. SPAQ procured by Malaria Consortium for 2024 will be used in 2025, so no additional medicines will need to be procured." Malaria Consortium, 2025 SMC South Sudan budget

• 7

  GiveWell, Global Vaccines CEA, 2024 (unpublished).

• 8

  Malaria Consortium's initial proposal to GiveWell (unpublished) involved using SMC as a base layer on which to add interventions including immunization referral, chlorine distribution, ORS distribution, and malnutrition screening and referral.

• 9

  Malaria Consortium, conversations with GiveWell (unpublished).

• 10

  We discussed this possibility with Malaria Consortium. Malaria Consortium, conversation with GiveWell, August 24, 2024 (unpublished)

• 11

  "As for the South Sudan SPAQ, you are correct: UNICEF donated some unused SPAQ to the government of Sudan which needed to be used in 2024 as it was approaching its expiry date. The SPAQ we had procured for 2024 is therefore available for use in 2025…. If there was no SMC funding available for 2025, it is unlikely that the SPAQ would be used for any other purposes." Email from Malaria Consortium’s SMC Program Director to GiveWell, September 13, 2024 (unpublished)

• 12

  See the GBD 2021 data on which our model is based here. This data suggests under-5 malaria mortality of 0.35%, which our model then adjusts for:

  • (Downwards adjustment) The fact that children 0-3 months are not SMC-eligible.
  • (Downwards adjustment) The reduction in SMC-avertable mortality due to the rollout of malaria vaccines.
  • (Upwards adjustment) The additional indirect malaria deaths that we expect are SMC-avertable.

• 13

  See the subnational MAP estimates here. These produce an estimate for Northern Bahr El Ghazal of 160 under-5 malaria deaths per 100,000 people per year, versus 352 under-5 malaria deaths per 100,000 people per year in South Sudan nationally. 160/352 = 45%.

• 14

  Malaria Atlas Project (MAP), conversation with GiveWell, March 28, 2024 (unpublished).

• 15

  IHME's GBD 2021 model estimates that under-5 malaria mortality in Sudan is less than 10% (link requires sign-in) of that in South Sudan.

• 16

  See Republic of South Sudan Malaria Indicator Survey (MIS) 2017, section 1.4.5: Anaemia and malaria testing, p. 5

• 17

  "Only 60% of health facilities report into DHIS2, leading to underreporting of the malaria burden, which stands at 1.2% with a population of 12 million. The ongoing Sudan crisis has exacerbated this situation, with over 639,207 individuals, including South Sudanese returnees and Sudanese refugees, arriving as of April 2024. Furthermore, predictions for another significant flood event in the latter half of 2024 threaten to further endanger the already dire humanitarian situation.
  …
  At the same time, it is likely that conventional methods to estimate the cost-effectiveness of SMC may underestimate the effectiveness of SMC in humanitarian contexts. We believe that the malaria burden in those settings is often higher than what available data suggest due to the complexity of collecting data in such settings and the resulting paucity of reliable data. Due to population movement, poor housing conditions and lack of access to prompt treatment, there are also frequent malaria outbreaks, which may not be visible in the available data." Malaria Consortium, Proposal for South Sudan Survive and Thrive program (unpublished)

• 18

  "As mentioned yesterday, please find the 2025 budget for SMC in 2 counties (incl. 1 refugee camp) in South Sudan attached. You will observe a year-on-year cost reduction in our projections, however, not to the level you saw in the Uganda budget. At the current very limited scale, we don't think there is much scope for reducing the cost further." Email from Malaria Consortium’s SMC Program Director to GiveWell, August 16, 2024 (unpublished)

• 19
  • The total number of children targeted in the 2025 program in South Sudan is 77,680. Malaria Consortium, 2025 SMC South Sudan budget
  • Comparatively, other SMC programs by Malaria Consortium in recent years have had much higher target figures. For example, in 2024, Malaria Consortium's target population was approximately 2,180,000 children in Burkina Faso, 1,360,000 in Chad, and 11,500,000 in Nigeria. Target figures in Togo and Uganda were closer, at less than 1 million, though both were still more than double that of South Sudan. GiveWell, GiveWell's analysis of Malaria Consortium's cost per SMC cycle administered, 2024.

• 20

  Malaria Consortium, conversation with GiveWell (unpublished).

• 21
  • "The seasonal pattern of malaria transmission and disease burden in the area [Northern Bahr el Ghazal], coinciding with the peak of the rainy season, meets the current SMC eligibility criterion which requires that at least 60% of cases occur during a maximum of 4 months." Khan et al. 2024
  • SMC delivery occurs on a monthly cycle: "SMC is delivered in cycles at 28-day intervals. Each cycle involves giving children four doses of medicine over three days." GiveWell, Malaria Consortium – Seasonal Malaria Chemoprevention, 2024.
  • Our understanding based on the budget that Malaria Consortium submitted to GiveWell for their SMC program in South Sudan is that there will be 5 cycles supported in 2025. Malaria Consortium, 2025 SMC South Sudan budget
  • As a five-cycle course will cover five months, rather than four, we adjust our 60% baseline figure upwards and roughly estimate that 70% of malaria mortality will occur during the SMC season in South Sudan.

• 22

  For example, see this map of the Sahel, which does not include South Sudan.

• 23
  • "In South Sudan, SP molecular resistance is high, given that fully resistant haplotypes (IRNGE) were the most commonly found form. The high frequency of haplotypes related to SP resistance was similar to what has been described in neighbouring countries [11, 12, 22]." Molina-de la Fuente et al. 2023

• 24

  "This study aims to generate evidence on the effectiveness of SMC when delivered under programmatic conditions in an area with an unknown anti-malarial drug resistance profile in the Northern Bahr el-Ghazal region of South Sudan…A non-randomized quasi experimental study was conducted to compare an intervention county with a control county…Children in the intervention arm had 70% lower odds of caregiver-reported fever relative to those in the control arm during the one-month period prior to Wave 2 (OR: 0.30, 95% CI 0.12–0.70, p = 0.003), and 37% lower odds in Wave 3 (OR: 0.63, 95% CI 0.22–1.59, p = 0.306) after controlling for baseline difference between counties in Wave 1. Odds of caregiver-reported RDT-confirmed malaria were 82% lower in the previous 1-month period prior to Wave 2 (OR: 0.18, 95% CI 0.07–0.49, p = 0.001) and Wave 3 (OR: 0.18, 95% CI 0.06–0.54, p = 0.003)." Khan et al. 2024

  • We have not deeply investigated these results. It is possible that the implied effect size of SMC on malaria cases among children receiving treatment is even higher than 82%.

• 25

  "At the same time, it is likely that conventional methods to estimate the cost-effectiveness of SMC may underestimate the effectiveness of SMC in humanitarian contexts. … the protective effectiveness of SMC in terms of preventing malaria disease in young children reported in the literature typically refers to the additive effect of SMC in addition to standard prevention strategies, especially mosquito nets. However, access to those strategies cannot be assumed in humanitarian settings, where mosquito net coverage, for example, tends to be low." Malaria Consortium, Proposal for South Sudan Survive and Thrive program (unpublished)

• 26We calculate this cost-effectiveness interval in our CEA by running a Monte Carlo simulation and taking the 25th and 75th percentile outcomes. Because this simulation is run whenever the CEA spreadsheet is opened, refreshed, or updated, and may produce different results each run, the numbers here may not exactly match what you see in our CEA.