Of all the infectious diseases currently plaguing humankind, there are perhaps only a few more difficult to diagnose than malaria. Caused by the parasitic protist Plasmodium , malaria infects over 200 million people each year in Sub-Saharan Africa, Asia, and South America (Howitt et al., 2012). Malaria is transmitted through mosquito bites, in which Plasmodium spends its growth phase (Nadjm and Behrens, 2012). After Plasmodium is transferred into a human host, it infects the liver cells and reproduces asexually for a period of 8 to 30 days (Vaughan, Aly and Kappe, 2008). After this incubation period, the malarial liver cells rupture, releasing thousands of parasites that then go on to infect red blood cells. The parasites replicate within the red blood cells, and periodically rupture their host cell to infect new cells (Figure 1). This replicate and rupture cycle continues until the death of the host (Bledsoe, 2005).
Figure 1: Malaria parasites spend their growth phase in the salivary glands of a mosquito, which are then transmitted into a human host through a mosquito bite, and replicate in the liver and red blood cells.
Due to the exponential increase of parasites over time, an early diagnosis is essential for successful treatment (Wongsrichanalai et al., 2007). Symptomatically, early-stage malaria is identical to the flu, septicemia, gastroenteritis and other viruses. It is therefore difficult to diagnose malaria based on symptoms alone (Nadjm and Behrens, 2012). The current standard for the diagnosis of malaria uses the Giemsa stain to bind to phosphate group sites found in DNA, and examining the red blood cells under a microscope (Wongsrichanalai et al., 2007). Infected cells will be stained, as red blood cells do not contain DNA. While Giemsa microscopy is an accurate diagnostic test for malaria, it requires sterile conditions, a medical laboratory and trained personnel, which are not readily found in the remote regions where malaria is endemic (Howitt et al., 2012). Thus, a more practical diagnostic test that is easily employable is of utmost importance to these areas.
Recent developments have yielded new insights into a noninvasive, transdermal technique for the diagnosis of malaria. This new technique is based on the presence of hemozoin, a unique nanoparticle formed from the digestion of hemoglobin by blood stage malaria parasites (Lukianova-Hleb et al., 2013). The small size and high optical absorbance of hemozoin allows a picosecond laser pulse to heat the hemozoin, which evaporates liquid to form a vapor nanobubble around the hemozoin. These vapor nanobubbles can then be detected using time-resolved optical scattering imaging (Figure 2), where a pulsed probe laser hits a photo detector. If hemozoin is present, the water-vapor boundary of the nanobubble scatters the pulse, and produces a unique signal (Lukianova-Hleb and Lapotko, 2012).
Figure 2: The nanobubble produces a distinct diffraction of the probe laser which can be detecting on a photoreceptor.
The use of hemozoin vapor nanobubbles as a diagnostic technique for malaria presents a novel method that addresses all the logistic issues associated with current standards. While current Giemsa microscopy techniques are time consuming and require reagents, qualified personnel and a blood sample, nanobubble detection occurs in seconds, requires no reagents, is noninvasive and can be made into a small inexpensive device. The development of this technology is essential in correctly diagnosing malaria in remote regions, and will help to provide timelier treatments to those who need it.
Works Cited:
Bledsoe, G.H., 2005. Malaria primer for clinicians in the United States. Southern medical journal, [online] 98(12), pp.1197–1204; quiz 1205, 1230. Available at: <http://www.ncbi.nlm.nih.gov/pubmed/16440920>.
Howitt, P. et al., 2012. Technologies for global health. Lancet, [online] 380(9840), pp.507–535. Available at: <http://www.ncbi.nlm.nih.gov/pubmed/22857974>.
Lukianova-Hleb, E.Y. et al., 2013. Hemozoin-generated vapor nanobubbles for transdermal reagent- and needle-free detection of malaria. Proceedings of the National Academy of Sciences. [online] Available at: <http://www.pnas.org/cgi/doi/10.1073/pnas.1316253111> [Accessed 18 Jan. 2014].
Lukianova-Hleb, E.Y. and Lapotko, D.O., 2012. Experimental techniques for imaging and measuring transient vapor nanobubbles. Applied Physics Letters, [online] 101(26), p.264102. Available at: <http://link.aip.org/link/APPLAB/v101/i26/p264102/s1&Agg=doi> [Accessed 18 Jan. 2014].
Nadjm, B. and Behrens, R.H., 2012. Malaria: an update for physicians. Infectious disease clinics of North America, [online] 26(2), pp.243–259. Available at: <http://www.ncbi.nlm.nih.gov/pubmed/22632637>.
Vaughan, A.M., Aly, A.S.I. and Kappe, S.H.I., 2008. Malaria parasite pre-erythrocytic stage infection: gliding and hiding. Cell host & microbe, [online] 4(3), pp.209–218. Available at: <http://www.ncbi.nlm.nih.gov/pubmed/18779047>.
Wongsrichanalai, C. et al., 2007. A review of malaria diagnostic tools: microscopy and rapid diagnostic test (RDT). The American journal of tropical medicine and hygiene, [online] 77(6 Suppl), pp.119–127. Available at: <http://www.ncbi.nlm.nih.gov/pubmed/18165483>.