Point-of-care quantification of blood-borne filarial parasites with a mobile phone microscope

Abstract

Parasitic helminths cause debilitating diseases that affect millions of people in primarily low-resource settings. Efforts to eliminate onchocerciasis and lymphatic filariasis in Central Africa through mass drug administration have been suspended because of ivermectin-associated serious adverse events, including death, in patients infected with the filarial parasite Loa loa. To safely administer ivermectin for onchocerciasis or lymphatic filariasis in regions co-endemic with L. loa, a strategy termed "test and (not) treat" has been proposed whereby those with high levels of L. loa microfilariae (>30,000/ml) that put them at risk for life-threatening serious adverse events are identified and excluded from mass drug administration. To enable this, we developed a mobile phone-based video microscope that automatically quantifies L. loa microfilariae in whole blood loaded directly into a small glass capillary from a fingerprick without the need for conventional sample preparation or staining. This point-of-care device automatically captures and analyzes videos of microfilarial motion in whole blood using motorized sample scanning and onboard motion detection, minimizing input from health care workers and providing a quantification of microfilariae per milliliter of whole blood in under 2 min. To validate performance and usability of the mobile phone microscope, we tested 33 potentially Loa-infected patients in Cameroon and confirmed that automated counts correlated with manual thick smear counts (94% specificity; 100% sensitivity). Use of this technology to exclude patients from ivermectin-based treatment at the point of care in Loa-endemic regions would allow resumption/expansion of mass drug administration programs for onchocerciasis and lymphatic filariasis in Central Africa.

Evaluation of Malaria Diagnoses Using a Handheld Light Microscope in a Community-Based Setting in Rural Côte d'Ivoire

“…17,18 Newer models of handheld and mobile-phonebased microscopes have recently been designed and evaluated for several infections with global health significance, including malaria, schistosomiasis, soil-transmitted helminthiasis, giardiasis, and Loa loa. [8][9][10]12,13,19,20 To date, most of these studies have been conducted in controlled laboratory settings, and the few field studies conducted used expert microscopists to operate novel diagnostic tools. Digitization of images (in this case, with a mobile phone camera) may be useful for several reasons, including integrating machine learning software for automated identification and quantification of pathogens, or for automated diseases mapping with geographic information systems.…”

“…In addition, future studies should focus on field applications of mobile-phone attachments harnessing computer learning technology for the automated identification and quantification of pathogens. 19,20 Finally, our study was conducted in a region of very high malaria prevalence and the majority of our population had low-grade parasitemia. Future studies should evaluate the operating characteristics of the Newton Nm1 microscope in regions with lower malaria prevalence.…”

Cellphone-based diagnostic devices

“…Cellphones especially outweigh over others in terms of their convenience in myriad situations in mundane life. It is no wonder that researchers have pursued their use as compelling measurement devices for examination, data collection, and transmission in and from remote and resource-limited settings [24][25][26][27]. When it comes to health care exploration, cellphones may bridge existing gaps between patients and timely, affordable healthcare, especially in more remote regions.…”

“…Since then, they have dedicated their efforts to the development of practical cellphone-based microscopy, something they call "CellScope" [30]. CellScope devices were designed for imaging granulocyte and red blood cells and performed high degrees of sensitivity and specificity in clinical Schistosoma haematobium infection diagnosis and blood-borne filarial parasites inspection (e.g., Loa loa) ( Figure 2) [24,30,31]. In other developments, Prof. Ozcan's group at UCLA presented the first cellphone-based lens-free holographic microscopy (without an additional lens-based attachment) in 2010 ( Figure 1B) [32].…”

Towards autonomous lab-on-a-chip devices for cell phone biosensing

“…Thus, the same type of instrument regularly interfaced to computers could be implemented with cell phones, either integrating the electronic interfacing (Nemiroski et al, 2014;Li et al, 2012;D'Ambrosio et al, 2015;Laksanasopin et al, 2015;Tropea et al, 2014;Addae-Mensah et al, 2010) or using generic digital acquisition boards for phones (https://github.com/ytai/ioio/wiki). This alternative implies complete freedom to design the instrumentation but sacrifices the ubiquity of the solution.…”