Journal Article
. 2013 Dec; 7(12):e2547.
doi: 10.1371/journal.pntd.0002547.

On-chip imaging of Schistosoma haematobium eggs in urine for diagnosis by computer vision

Ewert Linder 1 Anne Grote  Sami Varjo  Nina Linder  Marianne Lebbad  Mikael Lundin  Vinod Diwan  Jari Hannuksela  Johan Lundin  
Affiliations
  • PMID: 24340107
  •     39 References
  •     19 citations

Abstract

Background: Microscopy, being relatively easy to perform at low cost, is the universal diagnostic method for detection of most globally important parasitic infections. As quality control is hard to maintain, misdiagnosis is common, which affects both estimates of parasite burdens and patient care. Novel techniques for high-resolution imaging and image transfer over data networks may offer solutions to these problems through provision of education, quality assurance and diagnostics. Imaging can be done directly on image sensor chips, a technique possible to exploit commercially for the development of inexpensive "mini-microscopes". Images can be transferred for analysis both visually and by computer vision both at point-of-care and at remote locations.

Methods/Principal Findings: Here we describe imaging of helminth eggs using mini-microscopes constructed from webcams and mobile phone cameras. The results show that an inexpensive webcam, stripped off its optics to allow direct application of the test sample on the exposed surface of the sensor, yields images of Schistosoma haematobium eggs, which can be identified visually. Using a highly specific image pattern recognition algorithm, 4 out of 5 eggs observed visually could be identified.

Conclusions/Significance: As proof of concept we show that an inexpensive imaging device, such as a webcam, may be easily modified into a microscope, for the detection of helminth eggs based on on-chip imaging. Furthermore, algorithms for helminth egg detection by machine vision can be generated for automated diagnostics. The results can be exploited for constructing simple imaging devices for low-cost diagnostics of urogenital schistosomiasis and other neglected tropical infectious diseases.

Cross reacting antibodies against keyhole limpet haemocyanin may interfere with the diagnostics of acute schistosomiasis.
C Thors, E Linder.
Parasite Immunol, 1998 Nov 03; 20(10). PMID: 9797510
Schistosomiasis: number of people treated in 2009.
Wkly Epidemiol Rec, 2011 Mar 15; 86(9). PMID: 21395186
An in-depth analysis of a piece of shit: distribution of Schistosoma mansoni and hookworm eggs in human stool.
Stefanie J Krauth, Jean T Coulibaly, +3 authors, Jürg Utzinger.
PLoS Negl Trop Dis, 2013 Jan 04; 6(12). PMID: 23285307    Free PMC article.
Schistosomiasis in Swedish travellers to sub-Saharan Africa: Can we rely on serology?
Cecilia Thors, Per Holmblad, +2 authors, Ewert Linder.
Scand J Infect Dis, 2006 Aug 30; 38(9). PMID: 16938734
Optical imaging techniques for point-of-care diagnostics.
Hongying Zhu, Serhan O Isikman, +2 authors, Aydogan Ozcan.
Lab Chip, 2012 Oct 10; 13(1). PMID: 23044793    Free PMC article.
Review.
Malaria diagnosis and treatment: one size does not fit all.
Chris Drakeley, Roly Gosling, Hugh Reyburn.
PLoS Med, 2005 Jun 24; 2(6). PMID: 15971939    Free PMC article.
Mobile healthcare information management utilizing Cloud Computing and Android OS.
Charalampos Doukas, Thomas Pliakas, Ilias Maglogiannis.
Annu Int Conf IEEE Eng Med Biol Soc, 2010 Nov 26; 2010. PMID: 21097207
Malaria misdiagnosis: effects on the poor and vulnerable.
Mark Amexo, Rachel Tolhurst, Guy Barnish, Imelda Bates.
Lancet, 2004 Nov 24; 364(9448). PMID: 15555670
Highly Cited.
Image processing and pattern recognition algorithms for evaluation of crossed immunoelectrophoretic patterns (crossed radioimmunoelectrophoresis analysis manager; CREAM).
I Søndergaard, L K Poulsen, M Hagerup, K Conradsen.
Anal Biochem, 1987 Sep 01; 165(2). PMID: 3425908
Unleashing "civilian power": a new American diplomacy through neglected tropical disease control, elimination, research, and development.
Peter J Hotez.
PLoS Negl Trop Dis, 2011 Jul 09; 5(6). PMID: 21738802    Free PMC article.
Sub-pixel resolving optofluidic microscope for on-chip cell imaging.
Guoan Zheng, Seung Ah Lee, Samuel Yang, Changhuei Yang.
Lab Chip, 2010 Sep 30; 10(22). PMID: 20877904
Can the power of mobile phones be used to improve tuberculosis diagnosis in developing countries?
Mirko Zimic, Jorge Coronel, +3 authors, David A J Moore.
Trans R Soc Trop Med Hyg, 2008 Nov 28; 103(6). PMID: 19036392
Medical decision making: the family-doctor-patient triad.
Fawad Aslam, Omar Aftab, Naveed Z Janjua.
PLoS Med, 2005 Jun 24; 2(6). PMID: 15971934    Free PMC article.
Transmission control for schistosomiasis - why it matters now.
Charles H King, Robert F Sturrock, H Curtis Kariuki, Joseph Hamburger.
Trends Parasitol, 2006 Oct 13; 22(12). PMID: 17030017
Review.
Viewpoint: the neglect of stool microscopy for intestinal parasites and possible solutions.
S C Parija, H Srinivasa.
Trop Med Int Health, 1999 Sep 02; 4(7). PMID: 10470345
Cell-phone-based platform for biomedical device development and education applications.
Zachary J Smith, Kaiqin Chu, +7 authors, Sebastian Wachsmann-Hogiu.
PLoS One, 2011 Mar 15; 6(3). PMID: 21399693    Free PMC article.
FLOTAC: new multivalent techniques for qualitative and quantitative copromicroscopic diagnosis of parasites in animals and humans.
Giuseppe Cringoli, Laura Rinaldi, Maria Paola Maurelli, Jürg Utzinger.
Nat Protoc, 2010 Mar 06; 5(3). PMID: 20203667
Highly Cited.
Improving microscope quality is a good investment for under-resourced laboratories.
C Opoku-Okrah, R Rumble, G Bedu-Addo, I Bates.
Trans R Soc Trop Med Hyg, 2001 Jan 02; 94(5). PMID: 11132395
A European network for virtual microscopy--design, implementation and evaluation of performance.
Mikael Lundin, Janusz Szymas, +11 authors, Johan Lundin.
Virchows Arch, 2009 Mar 13; 454(4). PMID: 19280223
[The challenge to public health of the Millenium Development Goals: an approach from political epidemiology].
Diana Gil González, Marco Palma Solís, +4 authors, Carlos Alvarez-Dardet Díaz.
Gac Sanit, 2007 Apr 17; 20 Suppl 3. PMID: 17433202
Diagnostic dilemmas in helminthology: what tools to use and when?
Robert Bergquist, Maria Vang Johansen, Jürg Utzinger.
Trends Parasitol, 2009 Mar 10; 25(4). PMID: 19269899
Highly Cited.
Treatment of urinary schistosomiasis: methodological issues and research needs identified through a Cochrane systematic review.
A Danso-Appiah, P Garner, P L Olliaro, J Utzinger.
Parasitology, 2009 Jun 06; 136(13). PMID: 19493363
Systematic Review.
Imaging without lenses: achievements and remaining challenges of wide-field on-chip microscopy.
Alon Greenbaum, Wei Luo, +6 authors, Aydogan Ozcan.
Nat Methods, 2012 Sep 01; 9(9). PMID: 22936170    Free PMC article.
Highly Cited.
Rescuing the bottom billion through control of neglected tropical diseases.
Peter J Hotez, Alan Fenwick, Lorenzo Savioli, David H Molyneux.
Lancet, 2009 May 05; 373(9674). PMID: 19410718
Highly Cited. Review.
Diagnosis and management of schistosomiasis.
Darren J Gray, Allen G Ross, Yue-Sheng Li, Donald P McManus.
BMJ, 2011 May 19; 342. PMID: 21586478    Free PMC article.
Review.
Toward giga-pixel nanoscopy on a chip: a computational wide-field look at the nano-scale without the use of lenses.
Euan McLeod, Wei Luo, +2 authors, Aydogan Ozcan.
Lab Chip, 2013 Apr 18; 13(11). PMID: 23592185    Free PMC article.
Review.
Microscopic images transmitted by mobile cameraphone.
John Frean.
Trans R Soc Trop Med Hyg, 2007 Jul 31; 101(10). PMID: 17663014
Web-based virtual microscopy for parasitology: a novel tool for education and quality assurance.
Ewert Linder, Mikael Lundin, +6 authors, Johan Lundin.
PLoS Negl Trop Dis, 2008 Oct 23; 2(10). PMID: 18941514    Free PMC article.
Schistosomiasis in Africa: an emerging tragedy in our new global health decade.
Peter J Hotez, Alan Fenwick.
PLoS Negl Trop Dis, 2009 Sep 30; 3(9). PMID: 19787054    Free PMC article.
Highly Cited.
Neglected tropical diseases of the Middle East and North Africa: review of their prevalence, distribution, and opportunities for control.
Peter J Hotez, Lorenzo Savioli, Alan Fenwick.
PLoS Negl Trop Dis, 2012 Mar 06; 6(2). PMID: 22389729    Free PMC article.
Highly Cited. Review.
Urinary schistosomiasis on Pemba Island: low-cost diagnosis for control in a primary health care setting.
L Savioli, K E Mott.
Parasitol Today, 1989 Oct 01; 5(10). PMID: 15463144
Towards improved diagnosis of zoonotic trematode infections in Southeast Asia.
Maria Vang Johansen, Paiboon Sithithaworn, Robert Bergquist, Jürg Utzinger.
Adv Parasitol, 2010 Jul 16; 73. PMID: 20627143
Review.
From morbidity control to transmission control: time to change tactics against helminths on Unguja Island, Zanzibar.
Stefanie Knopp, J Russell Stothard, +4 authors, Jürg Utzinger.
Acta Trop, 2011 May 19; 128(2). PMID: 21586268
Laboratory medicine in Africa: a barrier to effective health care.
Cathy A Petti, Christopher R Polage, +2 authors, Merle A Sande.
Clin Infect Dis, 2006 Jan 05; 42(3). PMID: 16392084
Highly Cited. Review.
Mobile phone microscopy for the diagnosis of soil-transmitted helminth infections: a proof-of-concept study.
Isaac I Bogoch, Jason R Andrews, +4 authors, Jennifer Keiser.
Am J Trop Med Hyg, 2013 Mar 13; 88(4). PMID: 23478580    Free PMC article.
Parasites and poverty: the case of schistosomiasis.
Charles H King.
Acta Trop, 2009 Dec 08; 113(2). PMID: 19962954    Free PMC article.
Highly Cited. Review.
Prevention and control of schistosomiasis and soil-transmitted helminthiasis.
WHO Expert Committee.
World Health Organ Tech Rep Ser, 2003 Feb 21; 912. PMID: 12592987
Highly Cited.
Crowd-sourced BioGames: managing the big data problem for next-generation lab-on-a-chip platforms.
Sam Mavandadi, Stoyan Dimitrov, +4 authors, Aydogan Ozcan.
Lab Chip, 2012 Aug 25; 12(20). PMID: 22918378    Free PMC article.
Determining soil-transmitted helminth infection status and physical fitness of school-aged children.
Peiling Yap, Thomas Fürst, +3 authors, Peter Steinmann.
J Vis Exp, 2012 Sep 07; (66). PMID: 22951972    Free PMC article.
Fabricating low cost and high performance elastomer lenses using hanging droplets.
W M Lee, A Upadhya, P J Reece, Tri Giang Phan.
Biomed Opt Express, 2014 May 31; 5(5). PMID: 24877020    Free PMC article.
Low-cost motility tracking system (LOCOMOTIS) for time-lapse microscopy applications and cell visualisation.
Adam E Lynch, Junian Triajianto, Edwin Routledge.
PLoS One, 2014 Aug 15; 9(8). PMID: 25121722    Free PMC article.
A malaria diagnostic tool based on computer vision screening and visualization of Plasmodium falciparum candidate areas in digitized blood smears.
Nina Linder, Riku Turkki, +6 authors, Johan Lundin.
PLoS One, 2014 Aug 22; 9(8). PMID: 25144549    Free PMC article.
Quantitative evaluation of a handheld light microscope for field diagnosis of soil-transmitted helminth infection.
Isaac I Bogoch, Jason R Andrews, +5 authors, Jennifer Keiser.
Am J Trop Med Hyg, 2014 Sep 24; 91(6). PMID: 25246697    Free PMC article.
Diagnosis of Schistosoma haematobium infection with a mobile phone-mounted Foldscope and a reversed-lens CellScope in Ghana.
Richard K D Ephraim, Evans Duah, +6 authors, Isaac I Bogoch.
Am J Trop Med Hyg, 2015 Apr 29; 92(6). PMID: 25918211    Free PMC article.
Advances in the Diagnosis of Human Schistosomiasis.
Kosala G A D Weerakoon, Geoffrey N Gobert, Pengfei Cai, Donald P McManus.
Clin Microbiol Rev, 2015 Aug 01; 28(4). PMID: 26224883    Free PMC article.
Highly Cited. Review.
Review of Telemicrobiology.
Daniel D Rhoads, Blaine A Mathison, +2 authors, Liron Pantanowitz.
Arch Pathol Lab Med, 2015 Sep 01; 140(4). PMID: 26317376    Free PMC article.
Review.
Rapid infectious diseases diagnostics using Smartphones.
Matthew Bates, Alimuddin Zumla.
Ann Transl Med, 2015 Oct 22; 3(15). PMID: 26488011    Free PMC article.
Smartphone Microscopy of Parasite Eggs Accumulated into a Single Field of View.
Stephen J Sowerby, John A Crump, +2 authors, Philip C Hill.
Am J Trop Med Hyg, 2015 Nov 18; 94(1). PMID: 26572870    Free PMC article.
Disposable optics for microscopy diagnostics.
Pauliina Vilmi, Sami Varjo, +2 authors, Tapio Fabritius.
Sci Rep, 2015 Nov 21; 5. PMID: 26586153    Free PMC article.
Mobile Diagnostics Based on Motion? A Close Look at Motility Patterns in the Schistosome Life Cycle.
Ewert Linder, Sami Varjo, Cecilia Thors.
Diagnostics (Basel), 2016 Jun 21; 6(2). PMID: 27322330    Free PMC article.
Accuracy of Mobile Phone and Handheld Light Microscopy for the Diagnosis of Schistosomiasis and Intestinal Protozoa Infections in Côte d'Ivoire.
Jean T Coulibaly, Mamadou Ouattara, +6 authors, Isaac I Bogoch.
PLoS Negl Trop Dis, 2016 Jun 28; 10(6). PMID: 27348755    Free PMC article.
Mobile-phone and handheld microscopy for neglected tropical diseases.
Jason Rajchgot, Jean T Coulibaly, +5 authors, Isaac I Bogoch.
PLoS Negl Trop Dis, 2017 Jul 07; 11(7). PMID: 28683127    Free PMC article.
Evaluation of a Mobile Phone-Based Microscope for Screening of Schistosoma haematobium Infection in Rural Ghana.
Isaac I Bogoch, Hatice C Koydemir, +5 authors, Aydogan Ozcan.
Am J Trop Med Hyg, 2017 Jul 19; 96(6). PMID: 28719262    Free PMC article.
Point-of-care mobile digital microscopy and deep learning for the detection of soil-transmitted helminths and Schistosoma haematobium.
Oscar Holmström, Nina Linder, +7 authors, Johan Lundin.
Glob Health Action, 2017 Aug 26; 10(sup3). PMID: 28838305    Free PMC article.
"Smart Diagnosis" of Parasitic Diseases by Use of Smartphones.
Muhammad A Saeed, Abdul Jabbar.
J Clin Microbiol, 2017 Oct 20; 56(1). PMID: 29046408    Free PMC article.
Review.
International Society of Nephrology's 0by25 initiative (zero preventable deaths from acute kidney injury by 2025): focus on diagnosis of acute kidney injury in low-income countries.
Jochen G Raimann, Miguel C Riella, Nathan W Levin.
Clin Kidney J, 2018 Feb 10; 11(1). PMID: 29423195    Free PMC article.
Rapid Yeast Cell Viability Analysis by Using a Portable Microscope Based on the Fiber Optic Array and Simple Image Processing.
Weiming Wang, Hang Liu, +2 authors, Jun Yu.
Sensors (Basel), 2020 Apr 12; 20(7). PMID: 32276368    Free PMC article.
Aspects of Point-of-Care Diagnostics for Personalized Health Wellness.
Sandeep Kumar, Monika Nehra, +4 authors, Ki-Hyun Kim.
Int J Nanomedicine, 2021 Jan 26; 16. PMID: 33488077    Free PMC article.
Review.