Malaria and the ‘last’ parasite: how can technology help?

Abstract

Malaria, together with HIV/AIDS, tuberculosis and hepatitis are the four most deadly infectious diseases globally. Progress in eliminating malaria has saved millions of lives, but also creates new challenges in detecting the ‘last parasite’. Effective and accurate detection of malaria infections, both in symptomatic and asymptomatic individuals are needed. In this review, the current progress in developing new diagnostic tools to fight malaria is presented. An ideal rapid test for malaria elimination is envisioned with examples to demonstrate how innovative technologies can assist the global defeat against this disease. Diagnostic gaps where technology can bring an impact to the elimination campaign for malaria are identified. Finally, how a combination of microfluidic-based technologies and smartphone-based read-outs could potentially represent the next generation of rapid diagnostic tests is discussed.

Improving Accuracy of Malaria Diagnosis in Underserved Rural and Remote Endemic Areas of Sub-Saharan Africa: A Call to Develop Multiplexing Rapid Diagnostic Tests

“…However, it is not without limitations; for instance, it has a questionable sensitivity at low-level parasitaemia (≤50 parasitized erythrocytes/μl blood). Furthermore, due to inadequate facilities and/or lack of equipment and reliable electricity supply, combined with a shortage of experienced personnel, this approach becomes inaccessible in many primary healthcare centres in remote communities, locations where malaria may be extremely endemic [9,25] (Table 1).…”

“…Hence, two-thirds of the 276 million tests supplied to national malaria programs globally in 2017 detected P. falciparum only [6]. Notwithstanding the fact that most of the present generation of RDTs satisfy the WHO's guideline AS-SURED (Affordable, Sensitive, Specific, User-friendly, Rapid and Robust, Equipment-free, and Deliverable to end-users) criteria for appropriate diagnostic assays [9,37], there exist several restraints on their suitability for malaria diagnosis. ese include their inability to quantify parasite density, false-positive results due to persistence of Pf HRP-2 in the blood sample for several days after clearance of infection, false-negative results due to mutation (deletion) in the gene encoding Pf HRP-2 protein [25,36], and a high sensitivity threshold of approximately 200 parasitized erythrocytes/µl blood [23] (Table 1).…”

“…With a view to addressing this alarming situation, the WHO has set new goals for malaria reduction, including the fact that by the year 2030 there should be a reduction of global malaria incidence and mortality rates of at least 90%, as well as the elimination of the disease in at least 35 currently endemic countries [7]. In order to attain these ambitious targets, the strategies prioritized by the WHO were universal access to malaria prevention, drugs and diagnosis, elimination, and surveillance [8,9].…”

Lab-on-a-Chip Technologies for the Single Cell Level: Separation, Analysis, and Diagnostics

“…In case the target is not the entire cell, but a sub-cellular marker (e.g., DNA or RNA, individual antibodies [62] or other molecules) the cells containing the target molecule are lysed and/or the non-relevant cells are separated. After lysing the cells, their contents are optionally selectively multiplied (using e.g., polymerase chain reaction, PCR, and related techniques, like qPCR and nested PCR or Loop-mediated Isothermal Amplification, LAMP, and its derivatives like NINA-LAMP and LAMPport) and analyzed using chromatographic approaches (e.g., metabolomics, transcriptomics, proteomics, polyomics) or antibody-antigen binding, especially in rapid diagnostic tests (RDTs) [62]. This can all be done either in continuous phase microfluidics, droplet microfluidics, or paper-based microfluidics.…”

“…Some salient examples thereof are circulating tumor cells (CTC) of various types of cancer [1,[36][37][38], rare cells (e.g., sickle-cell variants of red blood cells) [39,40], parasites, like Plasmodium falciparum [1,7,10,11,[13][14][15][21][22][23]36,[41][42][43][44][45][46][47][48][49][50] and Trypanosoma spp. [8,44,[51][52][53][54][55][56][57] and even plant pathogens [26,58], as well as-after cells have been lysed-subcellular infection markers (e.g., DNA, RNA fragments) [10,11,22,43,[59][60][61][62]. Given the vast adaptability of microfluidics to any kind of single or multi-cellular assay [63], the ability to combine it with various light microscopy techniques…”