Diagnostics need systems : implementation and sustainability of sample-to-result platforms and conventional PCR in molecular diagnostics for low-resource settings

Abstract

Diagnostics are a neglected but essential part of any healthcare system, critical for individual and public health, but in low- and middle-income countries (LMICs), up to 80% of people lack access to diagnostics. Molecular diagnostics, the gold standard for many infectious diseases, remain especially underused despite the region's disproportionate disease burden, commonly attributed to high costs, infrastructure demands and the need for skilled personnel. Sample-to-result (S2R) platforms, integrating nucleic acid extraction, amplification, and analysis into a single closed cassette system, have been proposed as a technological solution to enable decentralized testing, yet their uptake remains largely confined to upper-middle-income countries and donor-funded vertical disease programs. The COVID-19 pandemic demonstrated that molecular diagnostic capacity can be built rapidly given sufficient funding and political will, raising the question of whether persistent challenges in low-resource settings are primarily technological or reflect deeper systemic limitations, addressed here by comparing experiences with S2R platforms and conventional real-time PCR in the Democratic Republic of the Congo (DRC), Cuba, and Peru with the available literature. A narrative review of commercially available S2R platforms found fairly good and similar performance across platforms in terms of ease-of-use and consumables, but differences in cost, distribution, and test panels tailored to LMIC needs. A multiplex HAT-ARBO assay was developed for simultaneous detection of T.b. gambiense, T.b. rhodesiense, chikungunya, dengue, and yellow fever virus on the ARIES (Luminex/Diasorin), showing satisfactory performance on retrospective and prospective samples in DRC. Implementation was stopped prematurely when the manufacturer discontinued the ARIES line, highlighting the risks of single-manufacturer dependence. A conventional multiplex RT-PCR was developed for Zika, chikungunya, dengue and yellow fever virus and implemented in an epidemiological study in Goma, DRC; tested retrospectively with good results at a reference laboratory in Havana and at a peripheral laboratory established during COVID-19; and used to evaluate dengue diagnostic approaches at a small hospital in the Peruvian Amazon, confirming the superiority of molecular diagnostics and feasibility of implementation at this health system level. Comparing both approaches, S2R platforms had the greatest impact on technological barriers at the laboratory level, but this effect was limited to the machine itself, leaving most systemic barriers unaddressed while increasing manufacturer dependence and cost. Conventional PCR offered greater flexibility in reagents and test menus. Framing diagnostic access as a technological problem obscures structural barriers to sustainable implementation; progress requires investing in resilient laboratory and health systems with sustainable financing and accountable governance.