Background Malaria rapid diagnostic tests (RDTs) are widely used to detect and treat malaria infections, yet a diagnostic gap remains. With turnaround times of ∼15 minutes, RDTs may be too slow to enable broad-scale implementation in certain contexts. Novel non-invasive diagnostics (NIDs) have potential to provide faster (<5 minutes), sensitive (90% for symptomatic, 65% for asymptomatic carriage), and cost-effective alternatives, which may increase testing throughput, enhance case detection, guide appropriate antimicrobial use, and reduce waste by using fewer consumables. Their potential impact has yet to be investigated.

Methods We modeled a country-agnostic population of 10 million individuals to assess the impact of population-level scale-up of four malaria testing strategies for active case-finding: 1) current practice (50% syndromic diagnosis and 50% RDTs), 2) full RDT scale-up, 3) full NID implementation, and 4) NID screening plus confirmatory RDT, using a decision-tree model of the malaria diagnostic and care cascade. We varied prevalence (0.02–0.25) and proportion of cases with symptoms (0.05–0.60) to evaluate strategy performance across epidemiological contexts. We investigated case detection rates, antimicrobial use, incremental cost-effectiveness ratios (ICERs) per disability adjusted life year (DALY) averted, net positive treatment outcomes, and threshold performance levels at which an NID would outperform RDTs.

Results Full NID implementation (strategy 3) yielded the highest case detection rates (up to 85%), followed by strategies 2, 4, and 1 (45%, 38%, 36% respectively). NID-based methods (strategies 3 and 4) saved costs and RDT scale-up was cost-effective at averting DALYs compared to current practice (ICERs: $60–1,270). Despite high case detection, universal NID testing spiked unnecessary antimicrobial use. Overall, our results suggest that an NID with 55% asymptomatic sensitivity and 84% specificity, followed by RDT confirmation (strategy 4), could simultaneously improve case detection, reduce antimicrobial overuse, and limit costs.

Conclusions This modeling analysis suggests that NIDs can sustainably optimize malaria case detection in symptomatic and asymptomatic cases and reduce costs, potentially making them a valuable addition to the diagnostic toolbox. When paired with confirmatory RDTs, they could help reduce inappropriate antimicrobial use, supporting drug efficacy amid rising resistance. Further research should assess their real-world utility, feasibility, and scalability for malaria surveillance and elimination efforts.

The authors have declared no competing interest.

This work received no external funding.

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