Wednesday, 17 April 2019 at 12:00 am
More than one-third of the world’s population – over 2.5 billion people – is at risk of Plasmodium vivax (P. vivax) malaria – the second most common species of malaria. P. vivax occurs in high burden countries but also accounts for over 70% of malaria cases in countries approaching elimination. It can cause severe disease and death, and represents a major financial burden to patients and their caregivers. High-risk groups include migrant populations, the rural poor, and other marginalized groups, as well as children under 5 who have the greatest chance of suffering negative health consequences as a result of their infection.
Following an initial P. vivax infection, parasites can lie dormant in a person’s liver, reawakening later to cause relapses of malaria. Relapses are an important source of morbidity and mortality and are a significant contributor to transmission. Full treatment of P. vivax malaria requires two treatments: one to treat the acute (blood-stage) infection and a second to clear malaria parasites from the liver and prevent relapse, also known as “radical cure”. Currently radical cure consists of daily primaquine treatment for 14 days, with resulting poor adherence. A further challenge is that primaquine can cause acute haemolytic anaemia (destruction of red blood cells) in patients with a hereditary deficiency of the enzyme glucose-6-phosphate dehydrogenase (G6PD). G6PD deficiency is a common genetic abnormality which ranges in prevalence and severity globally. Poor access to diagnostic testing for G6PD deficiency and resulting safety concerns have hampered the widespread use of primaquine.
Radical cure in children is further challenged by the unavailability of quality-assured primaquine in paediatric strengths and dosage forms. Barriers to the supply of paediatric primaquine include a small and fragmented market, lack of clarity on priority formulations, and technical challenges in developing low-dose scored tablets. In the absence of child-friendly primaquine, providers are faced with the option of splitting or crushing higher-dose pills and risking possible under/over dosing, or withholding primaquine altogether.
Several new tools are becoming available that have significant potential to improve P. vivax case management. In particular, a new radical cure drug – tafenoquine – will be available as a single dose. However, due to the potential for acute haemolytic anaemia in patients with G6PD deficiency, G6PD diagnostic testing with quantitative devices will be needed to determine eligibility for tafenoquine use. To support scale-up, a strong understanding will be needed of where tafenoquine can be used safely but still reach patients in need.
The scale-up of radical cure has the potential to significantly reduce relapse infections, onward transmission, and overall incidence of P. vivax malaria. It is an opportunity to reinforce efforts on malaria incidence and mortality, as well as to expand towards supporting malaria elimination – the third goal of the WHO Global Technical Strategy for Malaria 2016-2030.
Under this Call, Unitaid is soliciting proposals for the following interventions aimed at accelerating the availability, adoption and scale-up of improved tools to diagnose and treat P. vivax malaria, including:
Activities may include support for the market entry of paediatric tafenoquine, including additional studies as needed, and inclusion in country pilots when available. Separate, targeted work may support the availability of quality-assured primaquine in strengths and dosage forms appropriate for children. This could include incentivizing and supporting suppliers to bring quality-assured products to market, as well as providing suppliers with confidence in a viable market (e.g. through coordinated forecasting, consolidation of demand, etc.).
Pilot implementation should generate models for the introduction of new tools and approaches that optimize radical cure in terms of operational feasibility, safety and cost-effectiveness. The key question to be answered is where to deploy G6PD tests/tafenoquine as part of a broader radical cure strategy, recognizing that greater reach will be achieved at lower levels of care. Target countries should cover a range of geographical settings and levels of malaria endemicity.
Pilots should aim to enable the adoption of radical cure tools in target countries and provide a roadmap for the optimal deployment of G6PD testing, primaquine and tafenoquine, more broadly. This includes the generation of evidence to support operational guidance, with particular attention to ensuring the coordinated supply and distribution of quality-assured products needed for P. vivax case management. With the increased adoption of new tools as part of pilot implementation, opportunities for volume-based price reductions should also be explored.
Pilots should include the incorporation of new tools, such as more sensitive P. vivax RDTs, and paediatric tafenoquine, as these become available.
Demonstrated articulation with national programmes and other national and regional partners will be key to ensure that ownership extends beyond the life of the project. Emphasis should be placed on translating the outputs of the pilots into activities and tools that will support transition and broader scale up in project countries and beyond. This should not be limited to the final stages of the project but could aim to ensure strong national commitment to product adoption from the onset. As part of the broader sustainability objective, opportunities for co-funding of pilot implementation activities should be actively explored.
Applicants can submit proposals for one or both of the intervention areas outlined above. While the call aims to cover multiple geographic regions, proposals focused in countries within a single region will be considered.
Topics which are out of scope for this Call include: basic and early-stage research, single-country interventions and small-scale research studies.
Proposals submitted should clearly demonstrate the fit with the objectives set out above, the expected impact and value for money, as well as the complementarity and added value to similar projects and how coordination will be ensured.
If you intend to submit a proposal, please complete and send the [intention to submit (ISP) form PDF, 70 KB] to proposalsUnitaid@who.int by 04 March 2019.
The closing date for receipt of full proposals is 17 April 2019, at 12:00 noon Geneva (Switzerland) time. Applications received past the indicated deadline will not be considered.
N.B. A proposal is considered submitted only once you receive an e-mail message of confirmation of receipt from Unitaid. (Please note that this is not an automated message and confirmation will be sent after verification of your submission not earlier than 17 April 2019 and typically within one working day from receipt of a proposal).
Successful applicants should plan to be available for a face-to-face kick-off meeting with Unitaid, in Geneva, between 22-31 July (exact date tbc). In addition, successful applicants should plan to have sufficient human resources available to advance a first draft of the project plan by early September.
Unitaid works through market-based interventions to achieve global market and public health impact. Proposals should clearly demonstrate the use of innovative and sustainable approaches to accelerating access to better tools for P. vivax case management. Unitaid notes that this call may share some common elements or activities with other recent calls or ongoing Unitaid grants, and welcomes approaches that outline a coherent, integrated approach.
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.
