Formative research to inform development of a new diagnostic for soil-transmitted helminths: Going beyond the laboratory to ensure access to a needed product

Abstract

Soil-transmitted helminths (STHs) affect more than 1.5 billion people. The global strategy to control STH infections requires periodic mass drug administration (MDA) based on prevalence among populations at risk determined by diagnostic testing. Widely used copromicroscopy methods to detect infection, however, have low sensitivity as the prevalence and intensity of STH infections decline with repeated MDA. More sensitive diagnostic tools are needed to inform program decision-making. Using an integrated product development process, PATH conducted qualitative and quantitative formative research to inform the design and development of a more sensitive test for STH infections. The research, grounded in a conceptual framework for ensuring access to health products, involved stakeholder analysis, key opinion leader interviews, observational site visits of ongoing STH surveillance programs, and market research including market sizing, costing and willingness-to-pay analyses. Stakeholder analysis identified key groups and proposed strategic engagement of stakeholders during product development. Interviews highlighted features, motivations and concerns that are important for guiding design and implementation of new STH diagnostics. Process mapping outlined current STH surveillance workflows in Kenya and the Philippines. Market sizing in 2016 was estimated around half a million tests for lower STH burden countries, and 1–2 million tests for higher STH burden countries. The cost of commodities per patient for a molecular STH diagnostic may be around $10, 3–4 times higher than copromicroscopy methods, though savings may be possible in time and staffing requirements. The market is highly price sensitive as even at $5 per test, only 27% of respondents thought the test would be used by surveillance programs. A largely subsidized STH control strategy and a semi-functional Kato-Katz test may have created few incentives for manufacturers to innovate in STH diagnostics. Diverse partnerships, as well as balancing needs and expectations for new STH diagnostics are necessary to ensure access to needed products.

Sensitive and semiquantitative detection of soil-transmitted helminth infection in stool using a recombinase polymerase amplification-based assay

“…STH DNA from continuous worm shedding or from eggs that have been lysed is co-extracted, resulting in amplification of their DNA, and could increase parasite detection. Assuming optimal workflow and availability of at least four 8-tube isothermal devices, roughly 100 samples can be processed and analyzed in 4.8 to 6 hours depending on which sample extraction methodology is used [ 8 ].…”

“…Despite proving effective for parasite detection and quantification of infection intensity, multiplex RPA assays have several limitations. The cost is still high at around US $9–10 per test including the sample extraction step [ 8 ], which may prevent its uptake by control programs in low-resource settings. Substantially reducing the cost would enable broader use in affected countries.…”

“…Inaccurate diagnosis may underestimate the prevalence and intensity of infection and prevent a reliable estimation of MDA impact [ 7 ]. Monitoring the effectiveness of these programs and other interventions relies heavily on the accuracy of diagnostic tests to determine the presence and level of infection [ 8 ].…”

“…We developed a sensitive, field-deployable, RPA-based molecular tool (herein named Dx4STH) [ 8 ] for diagnosis of STH infection to improve decision-making on the frequency and duration of MDA to reduce the transmission and associated morbidity of STH infections. The RPA tests target four species of helminths using their ribosomal RNA gene targets.…”

Access to Chagas disease treatment in the United States after the regulatory approval of benznidazole

“…Access can be shaped by four activity streams: architecture (the organizational structure and relationships); availability (the supply components); affordability (the cost issues for various players); and adoption (demand factors and acceptance). This framework has been used, for instance, to identify access barriers to medicines for leishmaniasis in Africa [16] and to inform development of a new accessible diagnostic for soil-transmitted helminths [17].…”