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The goal of Project DIAMETER (Diagnostics for Malaria Elimination Toward Eradication) is to define the diagnostic needs unique to malaria elimination settings with sufficient clarity so that all stakeholders can act with confidence to develop, commercialize, and efficiently implement the most promising, costeffective, and impactful technologies for malaria elimination.Recent progress in malaria control has enabled countries to reduce malaria transmission rates. Existing diagnostic technologies—microscopy and rapid diagnostic tests (RDTs)—have played a critical role in this success by enabling many regions to achieve transmission rates near the threshold that defines the elimination phase. However, it is not clear whether these same tests are the most efficient and costeffective tools to achieve accurate infection detection at low levels of parasitemia which is critical to achieving elimination goals. Furthermore, there is a lack of clarity and agreement on the use scenarios, target product profiles, standardized methods of assay validation, and market potential for the malaria diagnostic tools best suited for cost-effective detection in elimination settings. The resulting ambiguity hinders the development of new infection detection technologies as well as strategic application of existing and nearly ready tools.PATH has developed a rigorous approach to identifying the most promising solutions to diagnostic challenges in low-resource settings. This involves aggregating and analyzing user needs, market needs, and technical requirements to generate the comprehensive evidence base necessary to inform program development, commercialization, and strategic program operations. Thus, through extensive field research and collaboration with malaria elimination experts, the DIAMETER team will evaluate and hone the use scenarios and target product profiles for infection detection in elimination scenarios. To this end, stakeholder interviews will be conducted in a selection of countries in Asia, Africa, and South America that are nearing malaria elimination. Information gathered will be collated to inform product development of new diagnostics and areas where further research is required. This report presents findings from stakeholder interviews conducted in Thailand in July 2013.

The goal of Project DIAMETER (Diagnostics for Malaria Elimination Toward Eradication) is to define the diagnostic needs unique to malaria elimination settings with sufficient clarity so that all stakeholders can act with confidence to develop, commercialize, and efficiently implement the most promising, costeffective, and impactful technologies for malaria elimination.Recent progress in malaria control has enabled countries to reduce malaria transmission rates. Existing diagnostic technologies—microscopy and rapid diagnostic tests (RDTs)—have played a critical role in this success by enabling many regions to achieve transmission rates near the threshold that defines the elimination phase. However, it is not clear whether these same tests are the most efficient and costeffective tools to achieve accurate infection detection at low levels of parasitemia, which is critical to achieving elimination goals. Furthermore, there is a lack of clarity and agreement on the use scenarios, target product profiles (TPPs), standardized methods of assay validation, and market potential for the malaria diagnostic tools best suited for cost-effective detection in elimination settings. The resulting ambiguity hinders the development of new infection detection technologies as well as strategic application of existing and nearly ready tools.PATH has developed a rigorous approach to identifying the most promising solutions to diagnostic challenges in low-resource settings. This involves aggregating and analyzing user needs, market needs, and technical requirements to generate the comprehensive evidence base necessary to inform product development, commercialization, and strategic program operations. Thus, through extensive field research and collaboration with malaria elimination experts, the DIAMETER team will evaluate and hone the use scenarios and TPPs for infection detection in elimination settings. To this end, stakeholder interviews will be conducted in a selection of countries in Asia, Africa, and South America that are nearing malaria elimination. Information gathered will be collated to inform product development of new diagnostics and areas where further research is required. This report presents findings from stakeholder interviews conducted in Zambia in August 2013.

As national malaria control programs contemplate their options for shifting tactics and tools to support malaria elimination,1 it is useful to compare and contrast how decreased transmission shifts the diagnostic focus:While control phase priorities aim to reduce the morbidity and mortality from malaria, elimination prioritizes driving human infection to zero. Thus, passive infection detection strategies that dominate a control program focus need to be augmented by active infection detection tactics in an elimination context.In an elimination context, parasite reservoirs are often characterized by lower density, sub-patent infections. Thus, tests capable of accurate detection at levels below that of traditional microscopy and rapid diagnostic tests (RDTs) are desired.Changes in malaria epidemiology that are associated with low transmission often result in clustered populations of both symptomatic and asymptomatic individuals that represent a transmission risk. To achieve the most efficient diagnostic and treatment coverage with active detection tactics targeting these groups, portable, point-of-care tests that provide rapid results without loss to follow-up are needed.Successful control programs targeting Plasmodium falciparum (P. falciparum; Pf) often result in a proportional increase in Plasmodium vivax (P. vivax; Pv), Plasmodium malariae (P. malariae; Pm), and Plasmodium knowlesi (P. knowlesi; Pk) and non-malaria febrile illness incidence – thus, differential diagnoses of individual malaria species from other febrile illness gain importance in the elimination context.The costs and risks associated with investigating and treating false positives in low prevalence, elimination settings increase the emphasis on diagnostic specificity.Decreased budgets and the cost of maintaining strong surveillance systems and national surveys emphasize the importance of cost-efficient diagnostic systems in elimination context.The risk of malaria strains developing resistance to drugs and detection emphasizes the importance of detect-and-treat programs with high levels of temporal efficiency. Thus, high coverage levels and high diagnostic sensitivities are paramount to expedient elimination.

Recent emphasis on elimination and eradication (E&E) goals for malaria programs is changing the way experts evaluate malaria diagnostic tools and tactics. As malaria prevalence is driven to lower levels, the focus pivots toward low-density, subclinical infections and geographically and demographically concentrated reservoirs. The proportions of species and subspecies found in these reservoirs may also change in favor of higher fitness phenotypes that are more difficult to diagnose and treat. These changes present both threats and opportunities to existing diagnostic technologies and those in the development pipeline. Furthermore, the evolution of new tactics to combat malaria in low-prevalence areas necessitates a review of technologies in the product development pipeline to encourage development of appropriate tools for new diagnostics use-scenarios. In light of shifting goals, epidemiology, and tactics, this report focuses on enzyme linked immunosorbent assays (ELISA) for histidine-rich protein 2 (HRP 2) for Plasmodium falciparum (P. falciparum) detection.

This report presents findings from a review of the market landscape conducted from December 2013 to February 2014 as part of PATH’s Project DIAMETER (Diagnostics for Malaria Elimination Toward Eradication). To date, evaluation of malaria diagnostics markets has been relatively limited, and where it is available, it is largely focused on passive case detection and on higher-burden countries. This report aims to build on existing malaria diagnostics market work and to complement it by delving deeper into elimination and active use scenarios for malaria diagnostics.The report is structured as follows:Malaria elimination and diagnostics use: This section provides information on elimination countries and the role of diagnostics, including a review of current World Health Organization (WHO) guidance and trends shaping the research agenda.The current malaria diagnostics market: This section summarizes relevant aspects of the current microscopy and rapid diagnostic test (RDT) markets, drawing on existing work about the malaria diagnostics market.Country use of diagnostics for elimination and active use scenarios: This section considers use of and demand for diagnostics in elimination settings, with a focus on active use scenarios. It includes both qualitative and quantitative analyses.The potential market for a new rapid infection detection test: This section describes a marketsizing exercise that was undertaken for a new rapid infection detection test (IDT).Promoting investment and development of a healthy market: This section describes challenges and risks along the product development and market access pathway and describes some potential interventions to promote investment and development of a healthy market.Several annexes provide additional detail of the analyses conducted for this report and a list of experts interviewed.The methodology undertaken is described at the start of each section. Generally, given the limited data available on malaria diagnostics markets, the methods for this report included identifying potential sources of data for analysis, desk review, and expert interviews. The available data on malaria diagnostics are limited (relative to other product categories, such as medicines), and even more limited for eliminating countries. Therefore, for this report, we primarily relied on national malaria control program reporting to the WHO (published and unpublished information). Although many national programs do not completely or reliably report to the WHO, the assumption was made that, by definition, surveillance systems in countries pursuing elimination should be robust enough to produce reliable data. Given the time frame for this report, validation of the data and analyses with countries and experts was not possible. When reviewing the analyses and data in this report, it is important to keep in mind that many of the analyses presented are for a subset of countries, and therefore may not be completely representative of the global markets. Attempts were also made to identify analogous products and markets; however, none were identified.From an operational research perspective, malaria elimination is a rapidly evolving area, and currently many unanswered questions about optimal strategies are being explored. Likewise, WHO guidance on elimination is expected to be updated in 2014. The lack of consensus and guidance on optimal approaches makes analyzing the market and making predictions about the market size for a new diagnostic challenging. Evidence gaps and research questions that would impact the market have been highlighted in this report.Lastly, a note about defining elimination countries: The WHO characterizes all countries by program phase using a combination of epidemiological and operational criteria. In 2013, the WHO classified 19 countries as in the elimination or pre-elimination phase, with an additional seven countries in the prevention of reintroduction phase. The Malaria Elimination Group (MEG) at the University of California, San Francisco (UCSF) has a broader definition of “malaria-eliminating countries,” which is based on whether a country has adopted a strategy for elimination. Currently, this is a set of 38 countries. For this report, the UCSF MEG definition and set of countries is used, unless otherwise noted.