Context

Vertical (mother-to-child) transmission of HIV, syphilis, and hepatitis B virus (HBV) contributes to significant morbidity and mortality in low- and middle-income countries (LMICs) and is targeted for elimination through an integrated approach. This vision for “Triple Elimination” is grounded in evidence demonstrating that linking interventions for HIV with services for other sexually transmitted infections, including syphilis and HBV, improves uptake and optimizes the use of limited resources. The three diseases also share many features, including their epidemiology, routes of transmission, and the core interventions for addressing them. In regions where Chagas is endemic, Triple Elimination is expanded to include congenital Chagas (‘EMTCT Plus’).

While eliminating vertical (mother-to-child) transmission has significant potential for global health impact, progress has been slow and the gains in reducing vertical transmission of HIV have not been realized for syphilis, HBV, or Chagas. Furthermore, limited experience has been documented on the optimal strategies for integration of services. The number of new neonatal HBV infections has remained roughly unchanged globally despite large reductions in infant infections achieved through vaccination. Chronic HBV infections cause approximately 820,000 HBV-related deaths annually and transmission during birth and early childhood are the most common timepoints for infection. Globally, there were an estimated 1 million pregnant women with syphilis infections in 2016, contributing to approximately 661,000 congenital syphilis cases and 355,000 adverse pregnancy outcomes, including over 200,000 early fetal and neonatal deaths—making congenital syphilis the second leading cause of preventable stillbirth and a greater cause of global child mortality than HIV. Vertical transmission of Chagas disease is estimated to cause about 9,000 new cases in newborns in Latin America annually, despite growing advocacy efforts. And finally, while prevention of vertical transmission of HIV has been a noteworthy achievement, progress has varied, and maternal antiretroviral treatment coverage has stagnated. Every day in 2022, an estimated 740 children became infected with HIV, and nearly 85% of these children live in sub-Saharan Africa.

While tools and interventions are available, there are key gaps in their use and implementation. Previously, syphilis screening was reliant on complex laboratory-based tests that limited access. Among the global adverse birth outcomes related to maternal syphilis infection, 57% occurred in pregnant women who attended antenatal care but were not screened for syphilis. Hepatitis B screening in antenatal care is even lower, with screening coverage at less than 20%. Newly available and underutilized rapid diagnostic tests (RDTs) have the potential to rapidly expand testing coverage. These tests, including single and dual HIV/syphilis RDTs and hepatitis B surface antigen (HBsAg) RDTs, as well as molecular diagnostics where relevant (e.g. early infant HIV diagnostics, HBV DNA tests), can detect and confirm infections during pregnancy and breastfeeding and support linkage to care, including counseling and follow-up. Efforts to catalyze adoption could leverage recent volume guarantees for combination HIV/syphilis RDTs with affordable pricing.[1]

Interventions to manage syphilis and hepatitis B during pregnancy are safe and efficacious, but in some cases, supply and delivery barriers limit access. Congenital syphilis can be averted with one dose of injectable benzathine penicillin G (BPG), but a limited supply base has triggered periodic and prolonged global shortages, including in 2023. The fragility of the market is also hampered by quality issues, low margins, fragmented demand and country-level supply and delivery issues. For hepatitis B, there are also supply security concerns given the limited number of quality-assured HBsAg RDT manufacturers. On the treatment side, tenofovir disoproxil fumarate (TDF) is available, but access to affordable generic TDF is often limited for patients who need it for HBV antiviral prophylaxis, and demand forecasting tends to focus only on HIV patients. Recent pricing agreements with TDF manufacturers offer potential for expanding access and can be built upon to help overcome this affordability barrier.[2]

Hepatitis B birth dose (HepB-BD) vaccination is another essential component to eliminating vertical transmission of HBV, and the most effective prevention strategy. However, coverage is highly variable, and less than 10% in Africa. While the vaccine is low-cost, it has significant logistical challenges. It should be delivered ideally within 24 hours of birth, posing difficulties in hard-to-reach areas or in countries where home-based births are common. In 2023, the Gavi Alliance Board approved support for a HepB-BD introduction program.[3] Efforts to coordinate with this initiative and define effective implementation models for introduction of the Hep-BD in these setting are a priority.

For Chagas, a key gap is access to timely newborn diagnosis and treatment. New and existing molecular tests have potential to expand access to rapid and accurate screening, which is critical for treatment success.  Pediatric formulations of benznidazole and nifurtimox exist for treatment, but availability is limited. Efforts are needed to introduce these technologies within EMTCT Plus programs in maternity wards in Latin America.

To address these challenges, catalytic action is needed to drive adoption of comprehensive and integrated elimination of vertical (mother-to-child) transmission programs within care platforms such as antenatal and postnatal care as well as at the community level. It is an opportune time to intervene as countries now have greater access to the normative guidelines, tools, and funding needed to make elimination possible, as well as strong leadership and political will reinforced by the elimination agendas of WHO and its Regional Offices such as AFRO and PAHO. Recent decisions from funders like the Global Fund to make Triple Elimination interventions eligible for inclusion in the 2023-2025 allocation period, and from Gavi to support introduction of the HepB-BD, represent new opportunities to strengthen the scalability pathway for these products. These efforts will be critical to achieving the goals and targets outlined in the new WHO Global Health Sector Strategies on HIV, viral hepatitis and STIs.

The main objectives of this Call for Proposals are the following:

• To support countries to design and deploy integrated elimination programming and generate evidence on effective and scalable implementation models in diverse settings.
• To overcome market barriers that limit access to critical commodities, including availability and affordability challenges impacting diagnostic and treatment products.
• To build demand for integrated elimination programs through people-centered and locally tailored roll-out approaches, including strong, funded community engagement, advocacy and literacy activities.

Call scope

Proposals are solicited for the following intervention.

Implementation work to accelerate demand and adoption of new and underutilized commodities for eliminating vertical (mother-to-child) transmission as part of integrated national strategies

Proposals should include large scale, multi-country implementation work to drive adoption of programs and recently available WHO guidelines. Activities should focus on developing pragmatic integrated approaches in a variety of contexts. Evidence generation on the feasibility, cost-effectiveness and impact of delivering an optimal mix of tools and delivery strategies will be critical for accelerating uptake and help provide a roadmap for introduction that overcomes traditional programmatic silos (e.g. HIV, STIs, Maternal and Child Health, Chagas, Immunization programs) and maximizes the overlap between tools and platforms. Program design should build on the recently launched WHO Framework for Triple Elimination and aim to capture lessons learned for how best to introduce, integrate, and transition to scale programs within care platforms, including antenatal and postnatal services. Context-specific optimal packages of interventions can leverage newly available and quality-assured screening and diagnostic tools, such as single and dual HIV/syphilis RDTs and HBV surface antigen (HBsAg) RDTs to quickly identify women at risk of vertical transmission and facilitate linkage to care. Activities should build on and integrate with existing systems such as integrated diagnostic platforms and data management systems. In Chagas endemic regions, packages could incorporate new or existing molecular screening platforms to accelerate treatment access. Innovations in service delivery should be considered, where there are opportunities to facilitate more rapid, consistent, and equitable access to interventions. This could include implementation research on:

• Delivery of integrated services for HIV, syphilis, HBV and Chagas (where endemic) within national programs, including optimal packages of care.
• Hepatitis B birth dose introduction, including strategies to reach infants born at lower-level facilities and in the community.
• Simplified hepatitis B screening and care strategies.
• Improved Chagas disease screening, diagnosis and treatment strategies for newborns.
• Self-care and self-testing approaches, particularly for syphilis, as well as partner and household testing and notification.
• Targeted behavioral interventions, informed by person-centered and differentiated service delivery approaches, to drive adoption among patients and care providers.

Efforts to identify scalable implementation models should also consider supply side gaps and market access barriers. This can include support to registration of new products at the country-level, as programming is included in national guidelines and strategies. Market assessments to investigate and help address product affordability and availability issues, such as the higher prices of TDF in some settings may be warranted. Targeted activities to mitigate supply security concerns, such as for BPG for syphilis treatment, including manufacturer engagement and support for regulatory and other quality approvals. This could be complemented by country-level supply chain assessments and optimization to ensure availability of commodities and resilient systems for eliminating vertical transmission. There are opportunities to leverage procurement volumes from the implementation pilots to support access to products at reduced prices. Other catalytic procurement mechanisms may be considered within the overall market shaping strategy, alongside activities to support comprehensive demand forecasting and quantification.

Strong stakeholder engagement throughout implementation will be critical to driving demand and adoption of elimination programs. Program design should be country-led and informed by meaningful engagement with community and civil society organizations. Implementation should incorporate person-centered strategies, such as targeted educational initiatives (e.g. support groups, peer mentoring), and other activities to build knowledge and reduce stigma and discrimination.  Targeted advocacy activities should also be included and be aimed at raising awareness and building political support for programs that are human rights-based and gender equitable. Proposals should demonstrate close coordination with national programs, regional bodies (e.g. AFRO, PAHO) and global scale-up partners (e.g. Global Fund, PEPFAR, Gavi, Global Financing Facility). As implementation in countries will be catalytic in nature and time-bound, efforts should be made to secure funding for transition to scale, including through donor-based and domestic financing.

To maximize impact, applicants are encouraged to consider implementation in countries in a range of geographies, but prioritizing settings with high disease burdens.  Delivery models should focus on how to reach the most vulnerable, including those accessing care at lower levels of the health system and the community level. Projects should generate scalable and sustainable implementation models that are transferable to other settings and enable scale-up potential in non-project countries.

Project Oversight

Technical input and oversight of the initiative will be shared across key partners, and to this end an expert advisory group or steering committee should be formed to oversee project activities at regional and global levels. The steering committee will be the strategic support structure for the grant, providing the lead grantee with thought partnership, a forum for problem-solving, relationship support, and evaluating strategic and/or operational shifts over the course of the project. The structure and design of this oversight body can be best defined during grant development to ensure it is fit-for-purpose.

Proposal requirements

Proponents should clearly describe their overall project design with a Theory of Change, showing how it meets the objectives of the initiative and how the proposed activities form part of a coherent whole. Proposals should explicitly state what impact will be achieved within the project life-time, as well as what, and how, lasting impact will be achieved.

It is expected that a consortium of partners will undertake the full complement of activities described. A focus on all four diseases is not required but this will be considered during proposal selection. The consortium should clearly demonstrate strong expertise in the different technical and market intervention areas needed to undertake the project, including the implementation of large-scale multi-country projects of this nature. Beyond the consortium, broad collaboration with relevant stakeholders will be vital to achieving the project objectives, including effective coordination mechanisms and well-articulated partnerships. Proponents should clarify the key stakeholders with whom they will engage, and how this will be achieved. It is important to include a country engagement model that outlines coordination and cooperation with countries in decision making around tailoring the design of elimination programs, monitoring introduction, and assessing impact. By actively involving government stakeholders in all phases of planning and implementation, projects will gain valuable insights into local contexts, policy frameworks, and stakeholder priorities. This collaboration will lead to more informed and effective project design, increased buy-in from government partners, and greater sustainability of project outcomes beyond the grant funding period.

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.

Additional information

Unitaid considers working with communities a critical part of generating demand and strongly encourages adopting inclusive approaches, and the early and continued meaningful 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 including ideation is essential, with this engagement a key determinant for success. Activities should be clearly budgeted in proposal submissions. Community-led approaches are important to consider and adequately fund and resource when designing, planning, implementing, and evaluating activities and programmes.

Unitaid sees value in proposals from South-based lead implementers with experience in leading the implementation of large-scale multi-country projects that support access to health products in LMICs. We also support the meaningful inclusion of South-based sub-implementers, where feasible and relevant, in proposed project implementation consortia. To be clear, Unitaid’s objective of progressively engaging an increased number of lead implementing partners from the global South does not preclude proposals that are led by or including partners from the global North. In all cases, we encourage coordination and collaboration across implementors and seek proposals with regional impact across key LMIC markets and a clear path to global impact.

Unitaid is committed to climate and environmental action in its investments and expects its partners to make similar commitments. Proposals should clearly indicate: (i) Efforts that will be made to minimize carbon emissions from project activities; (ii) Potential opportunities to contribute to broader climate and/or environmental co-benefits, in synergy with core project objectives. More detailed guidance and definitions are provided in the proposal template.

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: product development, single-country interventions.

Impact we are seeking

Through this Call for Proposals, Unitaid aims to reduce vertical (mother-to-child) transmission of HIV, syphilis, hepatitis B (HBV) and Chagas in endemic areas by driving the adoption of comprehensive and integrated elimination of vertical transmission programs. In particular, Unitaid seeks to:

• Support countries in the design, execution, and transition-to-scale of integrated elimination programs, including generating evidence on effective and scalable implementation models in diverse settings.
• Address market barriers by improving affordability, availability, and access to essential commodities for eliminating vertical transmission.
• Amplify demand for integrated elimination initiatives with community-driven, locally-adapted strategies.

The objectives outlined above will lead to: (1) improved maternal and neonatal health outcomes stemming from increased treatment coverage and the effectiveness of eliminating vertical (mother-to-child) transmission programs, (2) economic efficiencies within health systems through the expansion of integrated elimination strategies at primary care levels and through the deployment of new products, and (3) increased equitable access to cost-effective vaccines, diagnostics, and treatments in LMICs. The goal is to enable widespread access to a comprehensive care package through scale-up by governments and partners, to contribute to the global health response to diseases that predominantly affect mothers and children 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: 550 KB];
• Unitaid’s preliminary rationale for working in this area, please click here [PDF: 700 KB];
• Answers to frequently asked questions about Gavi’s Hepatitis B Birth Dose Programme, please click here and direct any follow-up questions to Gavi [PDF: 20 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.

[1] CHAI. MedAccess, CHAI, and SD Biosensor announce partnership to make dual rapid test for syphilis and HIV available for under US$1 in over 100 low- and middle-income countries. [Press release]. 2021 November 15. Available at: https://www.clintonhealthaccess.org/news/dual-syphilis-hiv-rdt-for-under-us1/.

[2] CHAI. CHAI and The Hepatitis Fund announce pricing breakthrough to reduce cost of viral hepatitis treatment by over 90 percent. [Press release] 2023 May 19. Available at: https://www.clintonhealthaccess.org/news/chai-and-the-hepatitis-fund-announce-pricing-breakthrough-to-reduce-cost-of-viral-hepatitis-treatment-by-over-90-percent/.

[3] Gavi. From rabies to hepatitis: Gavi to start rolling out new vaccines to lower-income countries. [Press release]. 2023 June 21. Available at: https://www.gavi.org/vaccineswork/kickstarting-essential-immunisation-roll-outs.

Important dates

Submission and format of proposals

• Proposal form with scanned version of signed Front page template, [DOC: 300 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:

• Guidance on Impact Assessment [PDF: 160 KB]
• Financial Guidelines for Unitaid Grantees [PDF: 1,2 MB]
• Unitaid Results Framework [PDF: 1.3 MB]
• Unitaid Scalability Framework [PDF: 466 KB]

Convocatoria de Propuestas: Acelerar la demanda y adopción de herramientas y estrategias integradas de entrega de servicios para la eliminación de la transmisión vertical del VIH, sífilis, hepatitis B y Chagas en áreas endémicas.

Webinar on this Call for Proposals: