PhD defence Anne Hauner

Supervisors

• Prof. dr. Kevin Ariën (ITM/University of Antwerp)

Abstract

Diagnostics are a neglected but essential part of healthcare systems, critical for both individual and public health. In low- and middle-income countries (LMICs) access to diagnostic services is highly inequitable. Molecular diagnostics, the gold standard for many infectious diseases, are especially underused in LMICs despite these countries' disproportionate disease burden, largely due to high costs, infrastructure demands, and the need for skilled personnel. Sample-to-result (S2R) platforms, which integrate nucleic acid extraction, amplification, and analysis into a single closed cassette system, have been proposed as a technological solution. Yet their uptake remains largely confined to upper-middle-income countries and donor-funded vertical disease programs. The COVID-19 pandemic showed 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.

This question is addressed by investigating how the implementation of S2R platforms and conventional real-time PCR affects the barriers and limitations of molecular diagnostics implementation, comparing experiences in the Democratic Republic of the Congo (DRC), Cuba, and Peru with those reported in the available literature.

Regarding the S2R platforms, a narrative review assessed the suitability of commercially available S2R platforms for use in LMIC. The platforms performed similarly in terms of ease-of-use and consumables, but differed in cost, distribution, and the availability of test panels tailored to LMIC needs. The ARIES (Luminex/Diasorin) was selected for implementation as it is an open S2R system that permits end-user-developed assays. A multiplex real-time RT-PCR (HAT-ARBO assay) was developed for simultaneous detection of T. b. gambiense, T. b. rhodesiense, chikungunya, dengue, and yellow fever viruses, and showed satisfactory performance in both retrospective and prospective clinical sample testing in Belgium and DRC. Implementation was, however, halted  prematurely when the manufacturer discontinued the ARIES product line, highlighting the risks of relying on a single-manufacturer.

Regarding conventional PCR, a multiplex real-time RT-PCR assay (ZYDC-PCR) was developed and validated for Zika, chikungunya, dengue, and yellow fever viruses, since commercial arboviral assays rarely include yellow fever virus. Following successful technical validation at ITM, the assay was implemented in various studies in different countries and settings. It was applied as a diagnostic tool in an epidemiological study in Goma, DRC; tested with retrospective samples with good results in the national reference laboratory in Havana; and implemented at a peripheral laboratory in Cienfuegos, in Cuba, demonstrating rapid assay adoption where infrastructure and trained personnel already exist. In Peru, the ZYDC-PCR was used to evaluate different diagnostic approaches for dengue in Yurimaguas, in the Peruvian Amazon, confirming the superiority of molecular diagnostics and the feasibility of implementation at this health system level. 

When comparing the impact of S2R platform and conventional PCR implementation, the S2R platforms, with their closed, automated cartridge system, had the greatest impact on technological barriers at the laboratory level, simplifying quality assurance and reducing both training requirements and contamination risk. This effect, however, is limited to the machine itself, while requirements for ancillary equipment, sample logistics, or supportive personnel remain unchanged. Most systemic barriers at the health systems and structural level persist, as S2R platform implementation has no effect on barriers, such as waste management, laboratory accreditations and governance. Furthermore, the proprietary system of S2R platforms increases manufacturer dependence for supplies, service and maintenance, and their higher costs can deepen the reliance on vertical disease programs. Conventional PCR, by contrast, offers greater flexibility in terms of reagents and test menu.

Framing access to molecular diagnostics as a technological problem, solvable through newer technologies, obscures the systemic and structural barriers limiting sustainable implementation. Where the necessary systemic conditions are already in place, conventional PCR, with its flexibility and adaptability, can actually offer advantages over S2R platforms in low-resource settings. Meaningful progress toward diagnostic access equity would therefore require moving away from a technology-as-silver-bullet mindset, and instead investing in resilient laboratory and health systems with sustainable financing and governance accountable to local populations.