Author(s): Eun-Taek Han 1
diagnostics; LAMP; malaria; novel molecular tools; Plasmodium
Malaria is the most devastating parasitic infection in the world, and it causes over 1 million deaths each year, mainly among children younger than 5 years, while high morbidity also results from the 350-500 million clinical malaria episodes. In particular, Plasmodium falciparum causes high mortality because of various complications and its increasing resistance to affordable antimalarials [1,2] . Prompt and accurate diagnostics are essential for the control and management of malaria in endemic and nonendemic areas [3,4] . In endemic countries, rapid and sensitive diagnostics are needed to identify infected patients and to prevent overprescription of antimalarial drugs on the basis of unreliable clinical diagnoses. In nonendemic countries, the lack of experience among physicians and laboratory technicians leads to delays and inaccurate diagnoses, which can result in a fatal prognosis for patients [5-7] . The misdiagnosis of malaria may overlook other potentially life-threatening illnesses, and it contributes to the emergence of drug-resistant malaria  . It is also increasingly unjustifiable because expensive artemisinin-based combination therapies (ACTs) are recommended as the first-line drug treatment in low-income endemic countries. The high cost of ACTs makes a specific diagnosis of malaria more cost-effective, which necessitates a more accurate diagnostic paradigm.
The vast volume of Plasmodium genome information and revolutionary biotechnological techniques are now being applied to the development of new malaria diagnostics  . However, there is still a gap between scientific advances and Plasmodium infection diagnostics in the field.
Accurate diagnosis is important for the appropriate treatment of malaria  . Existing tools for the diagnosis of malaria include microscopy, molecular tools, parasite antigen/enzyme detection kits (such as rapid diagnostic tests [RDTs]) and fluorochrome methods [3,11-13] . Each of these diagnostic tools has advantages and limitations (Table 1).
Light microscopy has relatively high sensitivity and specificity, and it also provides information on the parasite density, stage and species, but this method is labor intensive because it requires well-trained experts, which may result in therapeutic delays [14-19] . Very long observation periods and considerable expertise are required to make a correct diagnosis by microscopy in certain circumstances, such as low parasitemia and mixed infections, after drug treatment and during the chronic phase of infections.
Researchers have developed alternative malaria RDTs on the basis of parasite antigen-captured immunochromatographic technologies to facilitate rapid and accurate malaria diagnosis in areas where laboratory facilities are not available [11,20] . RDTs deliver a similar analytical sensitivity to expert microscopists [21,22] , although the sensitivity can vary among products  , while a species-specific product is commercially differentiate only for P. falciparum or non-P. falciparum .
In an attempt to detect malaria parasites in blood samples, automatic methods have been introduced. Certain fluorescent dyes and antibodies have an affinity or specific interaction for the nucleic acid in the nucleus and proteins of parasites. These techniques have an advantage for automated detection and high-throughput screening in laboratories of hospitals [24-30] ; however, are not suitable for field application.
Molecular detection methods including nested and real-time PCR, loop-mediated isothermal amplification (LAMP),...