Call for Proposals: Mitigating antimalarial drug resistance in Africa

Unitaid is pleased to announce this call for proposals aimed at mitigating antimalarial drug resistance in Africa through interventions that rapidly diversify artemisinin-based combination therapy (ACT) use.

Context

Antimalarial drug resistance in Africa is an urgent threat to the fight against malaria. To treat malaria, WHO recommends six artemisinin-based combination therapies (ACTs) that combine artemisinin-based compounds with a partner drug. Artemisinin partial resistance has been confirmed for the first time in Africa, specifically in Eritrea, Rwanda, and Uganda, though experts believe that the problem is likely more widespread. Artemisinin partial resistance increases the risk of de novo emergence of partner drug resistance, and importantly, the spread of parasites less sensitive to the partner drugs, which can result in clinical treatment failures. Given the heavy reliance on ACTs in Africa where most cases occur, and the risk resistance poses on our ability to deliver quality case management in the future, the threat of drug resistance must be addressed urgently. The seriousness of this threat has led global partners to mobilize rapidly before resistance leads to major setbacks.

New non-artemisinin-based treatments will not be available before 2026, and the most promising candidate (ganaplacide-lumefantrine) shares a partner drug with artemether-lumefantrine (AL), the most widely used ACT. Until this new drug is available, preserving the efficacy of lumefantrine is therefore a top priority. While ACTs continue to be the mainstay treatment for malaria, short-term resistance mitigation strategies focus on scaling-up and supporting the optimal use of quality ACTs alongside other efforts to mitigate resistance.

Even though multiple quality ACT options are available, the current ACT market is not optimally structured to limit drug pressure and overreliance on a single ACT is potentially driving resistance in Africa. Most African countries rely on AL as their first line treatment, and 30 African countries use AL exclusively. This is despite several countries including other ACTs in their treatment guidelines as possible first line options. As a result, AL’s share of donor-funded ACT procurements is over 80%. With such heavy reliance on AL, artemisinin partial resistance could instigate an emergency and trigger the rapid spread of lumefantrine resistance, causing a rise of cases and deaths, and potentially derailing the most advanced pipeline candidate.

Quickly diversifying ACT markets in countries to reduce drug pressure is a key approach recommended by WHO in their recently published strategy to respond to antimalarial drug resistance in Africa[1]. In the strategy, WHO also calls for research to close evidence gaps on innovative approaches (e.g., multiple first line ACTs) to better use current tools as well as research on how these approaches might address drivers of resistance. Diversifying ACT markets can be achieved through interventions that address supply barriers, create demand for ACTs with limited uptake, and generate evidence on strategies like multiple first-line treatments (MFTs) to mitigate resistance.

Newer ACTs, in particular artesunate-pyronadine (ASPY), offers opportunities to diversify the ACT market. ASPY became available in 2019, but despite having the advantage of once daily dosing, its uptake is low primarily due to its high price (three to four times the AL price), dosing by specific weight bands, and initial but now resolved safety concerns. ASPY’s price is driven by low volumes/poor demand, lack of competition, and high costs of the pyronadine active pharmaceutical ingredient (API). Dihydroartemisinin-piperaquine (DP) also has a reduced pill burden, and its market share has recently grown, however there is only one quality-assured supplier of the child-friendly formulation and prices are also three times that of AL. While it is susceptible to resistance due to the long half-life of piperaquine, close monitoring can ensure early detection and follow-on action.

Supply-side market shaping work is needed to improve the affordability of ASPY and increase suppliers/production capacity. Malaria partners are currently developing market interventions such as a volume guarantee and scoping the need for a co-payment that offsets higher prices. Other interventions being explored by partners include reducing the pyronadine API cost. Generating demand for ASPY is needed to grow the market and decrease prices. This includes early adoption support as well as testing new delivery approaches to close key evidence gaps. This would be complementary to other planned or potential efforts including a volume guarantee, pooled procurement, a co-payment, supporting new ASPY suppliers to enter the market, and technical assistance to countries to develop national policies and MFT treatment strategies.


[1] WHO launched the Strategy to respond to antimalarial drug resistance in Africa on the 18 November 2022 during World Antimicrobial Awareness Week (https://www.who.int/publications/i/item/9789240060265). The strategy proposes that countries, regional bodies and global partners address the threat through four pillars. In Pillar II WHO recommends quickly diversifying ACT markets in countries to reduce drug pressure.

Call scope

Tools

Under this Call, Unitaid will consider proposals that include support for the adoption and expanded use of ASPY and potentially other antimalarials as part of MFT strategies.

Areas of work

Proposals are being solicited for the following interventions:

Multi-country, large-scale product introduction support to accelerate demand and adoption of ASPY, and generate evidence for resistance management strategies like multiple first line ACTs.

Multi-country, large-scale product introduction support is needed to support ACT diversification. Support would serve to increase demand for ACTs with limited uptake i.e., ASPY, create early market volumes needed to support efforts of global health partners and to reduce prices, and in parallel address key knowledge gaps. The latter includes demonstrating how to implement ASPY alongside other ACTs while adhering to the specific dosing weight bands, as well as evaluating the feasibility, and cost-effectiveness/willingness to pay for multiple first-line treatment strategies. Strategies can include rotating ACTs, “mosaic” models, or diversifying ACTs by region or age group. Other innovative strategies that consider sub-national tailoring or implementing multiple first-line treatments across the public and private sectors could also be considered. As part of designing suitable strategies, country specific assessments of the ACT landscape are needed to guide approaches. Evidence generated from multi-country projects would therefore be important inputs into WHO policy recommendations and operational guidance, as well as generating evidence to support country-level scale-up.

In general, commodity costs for procurement volumes are assumed to be covered through routine country grants of the Global Fund and PMI. Consideration is being given to a time-limited co-payment or other market shaping interventions for ASPY to allow countries to deploy more expensive ACTs without compromising overall treatment coverage.

Settings of interest

  1. Countries with evidence of partial artemisinin resistance
    Priority countries are those where resistance has already been detected including Eritrea, Rwanda, Tanzania, Kenya and Uganda
  2. Countries with concerns of reduced or declined efficacy
    In countries such as Burkina Faso, the Democratic Republic of Congo, and Angola, treatment failures have recently been reported at some sites, however the method of detection used is not recommended by WHO. Until it is known whether methodological issues may have confounded results in these countries, these countries remain a potential concern, and there is still a need to reduce AL use while increasing the uptake of other available ACTs.
  3. Countries without evidence of partial artemisinin resistance or reduced efficacy
    In countries where resistance has yet to be reported, there is still a need to reduce the reliance on AL and remove barriers to utilizing other available ACTs. Countries for consideration include those with a high resistance risk, high malaria transmission rates, country willingness and readiness to diversify ACT use (e.g., product registration or existing inclusion in national guidelines), diversity of the implementation setting, and a country’s market size in relation to their ability to generate the volumes needed to achieve scale to lower prices.

Additional information

Unitaid considers working with communities a critical part of generating demand and strongly encourages adopting inclusive approaches, and the engagement of communities towards improving the lives and health of the most vulnerable people. The role of affected communities and planned collaborations with other relevant groups including grassroots community organizations and Civil Society Organizations at all stages of a project/programme is essential, this engagement can be a key determinant for success. Community-led approaches are important to consider when designing, planning, implementing, and evaluating activities and programmes.

Unitaid sees value in proposals from South-based implementors with experience in leading the implementation of large-scale multi-country projects that support access to health products in countries. We encourage coordination and collaboration across implementors and are interested in proposals that would have regional impact across Africa.

Unitaid is committed to climate and environmental action in its investments, and expect its partners to make similar commitments. Proposals should indicate: (i) Efforts that will be made to minimize carbon emissions from project activities (eg, greener procurement practices, reduced travel through more reliance on in-country based teams and service providers); (ii) Optional: potential opportunities to contribute to broader climate and/or environmental co-benefits, in synergy with core project objectives. Unitaid is open to consider limited funding when necessary to support such discrete activities, subject to Unitaid’s current and future guidelines and financial prioritization. Estimated budget requirements should be explicitly mentioned in the relevant section of the proposal form.

Proposals should be carefully targeted, reflecting focused interventions to address key challenges regarding mitigating antimalaria drug resistance in Africa and access to health products. Proposals are expected to target the specified area of work listed above. Proposals may, but do not have to, cover all activities described within the area of work. Proposals should clearly indicate the level of effort and budget for each activity.

Proposals should demonstrate value for money and measurable impact. Proposals should also include analysis of pathways to impact, scalability, and sustainability of key interventions.

Areas out of scope for this Call include proposals: a) product development; b) volume guarantees; and c) scaling-up artemether-lumefantrine (AL). Activities that are currently under investigation are also out of scope for this call, specifically expanding local manufacturing capacity for quality ASPY and DP.

Impact we are seeking

Through this Call for Proposals, Unitaid aims to improve access to health products of public health importance in low- and middle-income countries, and in particular:

  • To contribute to diversifying the use of health products in low- and middle- income countries (LMICs);
  • To increase their affordability in LMICs;
  • To generate demand and increase their adoption and use in LMICs;
  • To create guidance around multiple first-line treatment strategies for malaria.

The objectives outlined above will lead to: (1) better health outcomes due to additional people being treated, or due to people receiving effective treatments (2) financial savings/efficiencies due to the availability and use of more affordable products, and (3) improved and more equitable access by making products available and/or affordable in LMICs. The goal is to enable widespread access to affordable health products through scale-up by governments and partners, to contribute to the global health response to diseases that predominantly affect people in LMICs.

Process for proposal submission

When developing a proposal, please note the following resources:

  • Answers to frequently asked questions relevant to proposal development (this document is regularly updated), please click here [PDF: 100 KB, updated on 19 January 2023];
  • Unitaid’s preliminary rationale for working in this area, please click here [PDF: 900 KB];

Applicants should be clear about the underlying assumptions made in their proposed approach and should highlight any major risks or other factors that may affect the delivery of results. Finally, proposals are expected to outline a lean, concrete, and clear pathway to results and impact.

After assessment of the proposals and endorsement by the Unitaid Board all applicants will be officially notified as to whether they will be invited to develop a full grant agreement for Unitaid funding.

Important dates

16 January 2023

Unitaid will host a webinar to present the scope and content of the call for proposals and answer any process-related questions on Monday 16 January at 12:00 (noon) CET.

To register for the webinar please complete the online form here. Please note that the dial-in details will be sent a few hours before the start of the webinar to registered participants. Unitaid will endeavor to respond to questions; to facilitate this, you are encouraged to use the option to pose you questions during registration for the webinar.

If you are unable to participate in the webinar, a recording of the session will be made available at the bottom of this page shortly after the webinar takes place. Participation in the webinar is optional and you can respond to the call for proposals by sending your application at any point before the deadline indicated below.

11 August 2023

The closing date for receipt of full proposals is Friday 11 August 2023 at 12:00 (noon) CET. Applications received past the indicated deadline will not be considered. 

Please note, a proposal is considered submitted only once you receive an e-mail message of confirmation of receipt from Unitaid.

Please note that the confirmation of receipt is not an automated message and will be sent to you within one working day following the deadline. If for any reason you have not received the confirmation of receipt within one working day, please reach out to proposalsUnitaid@who.int. 

Please note that our email system accepts messages up to 8 MB in size. For submissions exceeding this size, please consider splitting your submission in several messages.

Submission and format of proposals

Proposals, including all annexes, should be submitted electronically to proposalsUnitaid@who.int. A full proposal consists of the following documents:

  • Proposal form with scanned version of signed Front page template, [DOC: 180 KB]
  • Annex 1: Log frame and GANTT chart template, [XLS: 278 KB]
  • Annex 2: Budget details template, [XLS: 24 KB]
  • Annex 3: Organizational details and CVs of key team members [no template]
  • Annex 4: Country engagement support Letters [no template]
  • Annex 5: Declaration of relevant interest template, [DOC: 21 KB]
  • Annex 6: Applicable ethics, anti-discrimination and environmental policies template, [DOC: 21 KB]
  • Annex 7: Declaration regarding tobacco entities template, [DOC: 24 KB]
  • Annex 8: Anti-Terrorism Declaration template, [DOC: 30 KB]
  • Annex 9: Audited financial statements for the past 3 years [no template]

If you have any questions about the application processes throughout any stage of the application review process, please send your queries to the Grant Application Manager:  proposalsUnitaid@who.int

You will find further guidance in the Unitaid proposal process document [PDF: 530 KB]. Additional guidance can be found in the following documents:


Webinar on this Call for Proposals:

 

Commodity access data on slide 10 contains data from the World malaria report 2021, and refers to public sector coverage i.e. only two thirds (69.3%) of children under five seek treatment for fever. In the public sector, 71% of children seeking care received treatment and only 39% received a malaria test. Data has since been updated in the World Malaria Report 2022.

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