DIAMETER: Diagnostics for malaria elimination toward eradication
Because the last malaria reservoirs may the hardest to detect
The goal of project DIAMETER is to catalyze and support the rapid development, commercialization, and implementation of the most promising, cost-effective, and impactful diagnostic technologies for malaria elimination.
Diagnostic tools used to reduce the morbidity and mortality of malaria in the control phase are less effective in achieving malaria elimination goals. Unfortunately, there is also a lack of clarity and agreement on the target product profiles (TPPs), standardized methods of assay validation, and market potential for the malaria diagnostic tools best suited for detection of low-density, asymptomatic infections. The resulting ambiguity hinders the development of new infection-detection technologies as well as strategic application of existing and nearly ready tools.
Many countries that have implemented successful malaria control programs aimed at reducing the burden of malaria are now interested in redirecting resources toward elimination with a sharpened focus on reduction of transmission. In support of this effort, health workers in these countries need to have access to appropriate technologies for infection detection. Accordingly, diagnostic developers and manufacturers need a clearer definition of the technical specifications and market potential for new products. Furthermore, policymakers need clarity on the accuracy, quality, and utility of available and forthcoming infection-detection technologies to implement their elimination and eradication strategies.
The DIAMETER team has implemented a rigorous approach to identify the most promising solutions to diagnostic challenges in low-resource settings. We aggregated and analyzed user and market needs as well as technical requirements to generate the comprehensive evidence base necessary to inform product development and commercialization of a highly sensitive infection-detection test (IDT).
Development of the target product profile
The following work streams comprised our thorough approach to the development of a TPP for an IDT for active-infection detection of malaria.
Taxonomy of use case scenarios
A use-case scenario is the outcome-oriented categorization of the interaction between a user, the setting, and a diagnostic tool. The use-case scenario taxonomy identified by the DIAMETER team was developed with input from desk research, discussions with stakeholders and experts, and field research.
To ensure that an improved diagnostic test is informed by the needs of users and the contexts in which active-infection detection is carried out, the DIAMETER team conducted field research in five representative countries (China, Ethiopia, Tanzania, Thailand, and Zambia) across the spectrum of regional programs ranging from control to elimination.
- China field report
- Ethiopia field report
- Tanzania (Zanzibar) field report
- Thailand field report
- Zambia field report
To identify the most efficient and cost-effective solutions for malaria infection-detection, the DIAMETER team assessed existing and new diagnostic tools in the product development pipeline with an emphasis on those tools that are adept at identifying asymptomatic, submicroscopic infections prevalent in elimination settings.
The resulting target product profile
In order to help bring clarity and objectivity to the innovation process, a common language is needed around uses of diagnostic tools in an elimination context. The TPP provides this common language and is a strategic planning tool that is updated throughout the development lifecycle and is therefore dynamic, facilitating communication among all stakeholders.
Utilizing our rigorous approach outlined above, the DIAMETER team developed a TPP for an IDT for active infection detection of malaria.
The proposed IDT is intended for qualitative detection of Plasmodium falciparum infections. Specifically, the test is intended for use in active-infection-detection interventions aimed at identifying and treating subclinical, low parasite density populations that serve as reservoirs of parasite biomass. The proposed IDT will use human blood from a finger-stick sample on a rapid diagnostic test (RDT) assay format and include histidine-rich protein 2 and one other Plasmodium falciparum antigen as targets.
We will continue to revise the TPP, incorporating stakeholder feedback and new information as it becomes available. We welcome your questions and feedback on the current revision.
With core funding from the Bill & Melinda Gates Foundation, our future activities focus on development of IDTs for qualitative detection of low-density Plasmodium falciparum infections. We envision that IDTs will be used by malaria elimination programs to identify and treat subclinical, low-parasite-density populations that propagate transmission. To achieve the IDT TPP specifications, we are currently evaluating the most promising immunochromatographic assay innovations.
Because malaria elimination does not lend itself to “one size fits all” solutions, the DIAMETER team is also pursuing collaborations for product development and access for promising malaria detection technologies including a disposable, infrastructure-free, electricity-free DNA/RNA test; enhanced microscopy systems that leverage digital image capture and pattern recognition software; and RDT data capture/reader technologies.
- The biophysical characterization of HRP2 reveals insights toward improved diagnostics for Plasmodium falciparum malaria elimination
- Guiding product development of malaria diagnostics to support elimination programs: The target product profile
- Assessing the market landscape for an infection detection test aimed at malaria elimination
- Structural characterization of Plasmodium falciparum HRP2: Analytical challenges in Plasmodium falciparum HRP2-based IDT development
- Incorporating user needs into product development for improved infection detection to support malaria elimination programs
Gonzalo Domingo, Malaria Portfolio Leader
This project is supported by a grant from the Bill & Melinda Gates Foundation.