Ultrasensitive Diagnostics for Low-Density Asymptomatic Plasmodium falciparum Infections in Low-Transmission Settings

The emergence of multidrug-resistant Plasmodium falciparum malaria in Southeast Asia (SEA) has accelerated regional malaria elimination efforts. Most malaria in this and other low-transmission settings exists in asymptomatic individuals, which conventional diagnostic tests lack the sensitivity to detect. This has led to the development of new ultrasensitive diagnostics that are capable of detecting these low-parasitemia infections. This review summarizes the current status of ultrasensitive technologies, including PCR and loop-mediated isothermal amplification (LAMP)-based methods, as well as a newly developed ultrasensitive rapid diagnostic test (uRDT). The sensitivity, specificity, and field performance of these platforms will be examined, as well as their suitability for use in resource-limited settings to aid in malaria elimination efforts. uRDTs, with their improved sensitivity, are now able to detect approximately half of asymptomatic infections, providing a useful point-of-contact tool for malaria surveillance. The increased sensitivity and high-throughput nature of PCR-based tests make them ideal for screening large populations in places where laboratory capacity exists, and the recent commercialization of malaria LAMP kits should facilitate their adoption as a public health tool in places where such infrastructure is lacking. Finally, recent advances with dried blood spots may enable utilization of the extensive laboratory infrastructure of higher-income countries to assist with molecular surveillance in support of malaria elimination. If malaria is to be eliminated in SEA and other low-endemicity regions, then ultrasensitive diagnostics will likely play a key role in identifying and clearing the vast asymptomatic pool of infections that are common to these regions.