Skip to main content
Top
Published in: Malaria Journal 1/2018

Open Access 01-12-2018 | Research

Automated microscopy for routine malaria diagnosis: a field comparison on Giemsa-stained blood films in Peru

Authors: Katherine Torres, Christine M. Bachman, Charles B. Delahunt, Jhonatan Alarcon Baldeon, Freddy Alava, Dionicia Gamboa Vilela, Stephane Proux, Courosh Mehanian, Shawn K. McGuire, Clay M. Thompson, Travis Ostbye, Liming Hu, Mayoore S. Jaiswal, Victoria M. Hunt, David Bell

Published in: Malaria Journal | Issue 1/2018

Login to get access

Abstract

Background

Microscopic examination of Giemsa-stained blood films remains a major form of diagnosis in malaria case management, and is a reference standard for research. However, as with other visualization-based diagnoses, accuracy depends on individual technician performance, making standardization difficult and reliability poor. Automated image recognition based on machine-learning, utilizing convolutional neural networks, offers potential to overcome these drawbacks. A prototype digital microscope device employing an algorithm based on machine-learning, the Autoscope, was assessed for its potential in malaria microscopy. Autoscope was tested in the Iquitos region of Peru in 2016 at two peripheral health facilities, with routine microscopy and PCR as reference standards. The main outcome measures include sensitivity and specificity of diagnosis of malaria from Giemsa-stained blood films, using PCR as reference.

Methods

A cross-sectional, observational trial was conducted at two peripheral primary health facilities in Peru. 700 participants were enrolled with the criteria: (1) age between 5 and 75 years, (2) history of fever in the last 3 days or elevated temperature on admission, (3) informed consent. The main outcome measures included sensitivity and specificity of diagnosis of malaria from Giemsa-stained blood films, using PCR as reference.

Results

At the San Juan clinic, sensitivity of Autoscope for diagnosing malaria was 72% (95% CI 64–80%), and specificity was 85% (95% CI 79–90%). Microscopy performance was similar to Autoscope, with sensitivity 68% (95% CI 59–76%) and specificity 100% (95% CI 98–100%). At San Juan, 85% of prepared slides had a minimum of 600 WBCs imaged, thus meeting Autoscope’s design assumptions. At the second clinic, Santa Clara, the sensitivity of Autoscope was 52% (95% CI 44–60%) and specificity was 70% (95% CI 64–76%). Microscopy performance at Santa Clara was 42% (95% CI 34–51) and specificity was 97% (95% CI 94–99). Only 39% of slides from Santa Clara met Autoscope’s design assumptions regarding WBCs imaged.

Conclusions

Autoscope’s diagnostic performance was on par with routine microscopy when slides had adequate blood volume to meet its design assumptions, as represented by results from the San Juan clinic. Autoscope’s diagnostic performance was poorer than routine microscopy on slides from the Santa Clara clinic, which generated slides with lower blood volumes. Results of the study reflect both the potential for artificial intelligence to perform tasks currently conducted by highly-trained experts, and the challenges of replicating the adaptiveness of human thought processes.
Appendix
Available only for authorised users
Literature
1.
go back to reference Laveran A. Traité des fiévres palustres, avec la description des microbes du paludisme. Paris: Octave Doin; 1884. Laveran A. Traité des fiévres palustres, avec la description des microbes du paludisme. Paris: Octave Doin; 1884.
2.
go back to reference Bruce-Chwatt LJ. Alphonse Laveran’s discovery 100 years ago and today’s global fight against malaria. J R Soc Med. 1981;74:531–6.CrossRef Bruce-Chwatt LJ. Alphonse Laveran’s discovery 100 years ago and today’s global fight against malaria. J R Soc Med. 1981;74:531–6.CrossRef
3.
go back to reference Zurovac D, Midia B, Ochola SA, English M, Snow RW. Microscopy and outpatient malaria case management among older children and adults in Kenya. Trop Med Int Health. 2006;11:432–40.CrossRef Zurovac D, Midia B, Ochola SA, English M, Snow RW. Microscopy and outpatient malaria case management among older children and adults in Kenya. Trop Med Int Health. 2006;11:432–40.CrossRef
4.
go back to reference Shiff CJ, Minjas J, Premji Z. The ParaSight-F test: a simple rapid manual dipstick test to detect Plasmodium falciparum infection. Parasitol Today. 1994;10:494–5.CrossRef Shiff CJ, Minjas J, Premji Z. The ParaSight-F test: a simple rapid manual dipstick test to detect Plasmodium falciparum infection. Parasitol Today. 1994;10:494–5.CrossRef
5.
go back to reference Dietze R, Perkins M, Boulos M, Luz F, Reller B, Corey GR. The diagnosis of Plasmodium falciparum infection using a new antigen detection system. Am J Trop Med Hyg. 1995;52:45–9.CrossRef Dietze R, Perkins M, Boulos M, Luz F, Reller B, Corey GR. The diagnosis of Plasmodium falciparum infection using a new antigen detection system. Am J Trop Med Hyg. 1995;52:45–9.CrossRef
6.
go back to reference Bell D, Peeling RW. Evaluation of rapid diagnostic tests: malaria. Nat Rev Microbiol. 2006;4:S34–8.CrossRef Bell D, Peeling RW. Evaluation of rapid diagnostic tests: malaria. Nat Rev Microbiol. 2006;4:S34–8.CrossRef
7.
go back to reference Poon LLM. Sensitive and inexpensive molecular test for Falciparum malaria: detecting Plasmodium falciparum DNA directly from heat-treated blood by loop-mediated isothermal amplification. Clin Chem. 2005;52:303–6.CrossRef Poon LLM. Sensitive and inexpensive molecular test for Falciparum malaria: detecting Plasmodium falciparum DNA directly from heat-treated blood by loop-mediated isothermal amplification. Clin Chem. 2005;52:303–6.CrossRef
8.
go back to reference Gamboa D, Ho M-F, Bendezu J, Torres K, Chiodini PL, Barnwell JW, et al. A large proportion of P. falciparum isolates in the Amazon region of Peru lack pfhrp2 and pfhrp3: implications for malaria rapid diagnostic tests. PLoS ONE. 2010;5:8091.CrossRef Gamboa D, Ho M-F, Bendezu J, Torres K, Chiodini PL, Barnwell JW, et al. A large proportion of P. falciparum isolates in the Amazon region of Peru lack pfhrp2 and pfhrp3: implications for malaria rapid diagnostic tests. PLoS ONE. 2010;5:8091.CrossRef
9.
go back to reference Wongsrichanalai C, Barcus MJ, Muth S, Sutamihardja A, Wernsdorfer WH. A review of malaria diagnostic tools: microscopy and rapid diagnostic test (RDT). Am J Trop Med Hyg. 2007;77:119–27.CrossRef Wongsrichanalai C, Barcus MJ, Muth S, Sutamihardja A, Wernsdorfer WH. A review of malaria diagnostic tools: microscopy and rapid diagnostic test (RDT). Am J Trop Med Hyg. 2007;77:119–27.CrossRef
10.
go back to reference WHO. Malaria microscopy quality assurance manual. Version 2. Geneva: World Health Organization; 2016. WHO. Malaria microscopy quality assurance manual. Version 2. Geneva: World Health Organization; 2016.
11.
go back to reference Maguire JD, Lederman ER, Barcus MJ, O’Meara WAP, Jordon RG, Duong S, et al. Production and validation of durable, high quality standardized malaria microscopy slides for teaching, testing and quality assurance during an era of declining diagnostic proficiency. Malar J. 2006;5:92.CrossRef Maguire JD, Lederman ER, Barcus MJ, O’Meara WAP, Jordon RG, Duong S, et al. Production and validation of durable, high quality standardized malaria microscopy slides for teaching, testing and quality assurance during an era of declining diagnostic proficiency. Malar J. 2006;5:92.CrossRef
12.
go back to reference WHO. Methods for surveillance of antimalarial drug effiacy. Geneva: World Health Organization; 2009. WHO. Methods for surveillance of antimalarial drug effiacy. Geneva: World Health Organization; 2009.
13.
go back to reference Ross NE, Pritchard CJ, Rubin DM, Dusé AG. Automated image processing method for the diagnosis and classification of malaria on thin blood smears. Med Biol Eng Comput. 2006;44:427–36.CrossRef Ross NE, Pritchard CJ, Rubin DM, Dusé AG. Automated image processing method for the diagnosis and classification of malaria on thin blood smears. Med Biol Eng Comput. 2006;44:427–36.CrossRef
14.
go back to reference Tek FB, Dempster AG, Kale I. Computer vision for microscopy diagnosis of malaria. Malar J. 2009;8:153.CrossRef Tek FB, Dempster AG, Kale I. Computer vision for microscopy diagnosis of malaria. Malar J. 2009;8:153.CrossRef
15.
go back to reference Gillet P, Bosselaers K, Cnops L, Bottieau E, Van Esbroeck M, Jacobs J. Evaluation of the SD FK70 malaria Ag Plasmodium vivax rapid diagnostic test in a non-endemic setting. Malar J. 2009;8:129.CrossRef Gillet P, Bosselaers K, Cnops L, Bottieau E, Van Esbroeck M, Jacobs J. Evaluation of the SD FK70 malaria Ag Plasmodium vivax rapid diagnostic test in a non-endemic setting. Malar J. 2009;8:129.CrossRef
16.
go back to reference Uguen C, Rabodonirina M, De Pina JJ, Vigier JP, Martet G, Maret M, et al. ParaSight-F rapid manual diagnostic test of Plasmodium falciparum infection. Bull World Health Organ. 1995;73:643–9.PubMedPubMedCentral Uguen C, Rabodonirina M, De Pina JJ, Vigier JP, Martet G, Maret M, et al. ParaSight-F rapid manual diagnostic test of Plasmodium falciparum infection. Bull World Health Organ. 1995;73:643–9.PubMedPubMedCentral
17.
go back to reference Vink JP, Laubscher M, Vlutters R, Silamut K, Maude RJ, Hasan MU, et al. An automatic vision-based malaria diagnosis system. J Microsc. 2013;250:166–78.CrossRef Vink JP, Laubscher M, Vlutters R, Silamut K, Maude RJ, Hasan MU, et al. An automatic vision-based malaria diagnosis system. J Microsc. 2013;250:166–78.CrossRef
18.
go back to reference WHO. Basic malaria microscopy. 2nd ed. Geneva: World Health Organization; 2010. WHO. Basic malaria microscopy. 2nd ed. Geneva: World Health Organization; 2010.
19.
go back to reference WHO. World malaria report 2016. Geneva: World Health Organization; 2017. WHO. World malaria report 2016. Geneva: World Health Organization; 2017.
20.
go back to reference Poostchi M, Silamut K, Maude R, Jaeger S, Thoma G. Image analysis and machine learning for detecting malaria. Transl Res. 2018;194:36–55.CrossRef Poostchi M, Silamut K, Maude R, Jaeger S, Thoma G. Image analysis and machine learning for detecting malaria. Transl Res. 2018;194:36–55.CrossRef
21.
go back to reference Loddo A, Di Ruberto C, Kocher M. Recent advances of malaria parasites detection systems based on mathematical morphology. Sensors. 2018;18:513.CrossRef Loddo A, Di Ruberto C, Kocher M. Recent advances of malaria parasites detection systems based on mathematical morphology. Sensors. 2018;18:513.CrossRef
22.
go back to reference Gopakumar GP, Swetha M, Sai Siva G, Sai Subrahmanyam GRK. Convolutional neural network-based malaria diagnosis from focus stack of blood smear images acquired using custom-built slide scanner. J Biophotonics. 2018;11:3.CrossRef Gopakumar GP, Swetha M, Sai Siva G, Sai Subrahmanyam GRK. Convolutional neural network-based malaria diagnosis from focus stack of blood smear images acquired using custom-built slide scanner. J Biophotonics. 2018;11:3.CrossRef
23.
go back to reference Abbas N, Saba T, Mohamad D, Rehman A, Almazyad AS, Al-Ghamdi JS. Machine aided malaria parasitemia detection in Giemsa-stained thin blood smears. Neural Comput Appl. 2018;29:803–18.CrossRef Abbas N, Saba T, Mohamad D, Rehman A, Almazyad AS, Al-Ghamdi JS. Machine aided malaria parasitemia detection in Giemsa-stained thin blood smears. Neural Comput Appl. 2018;29:803–18.CrossRef
24.
go back to reference Le M-T, Bretschneider TR, Kuss C, Preiser PR. A novel semi-automatic image processing approach to determine Plasmodium falciparum parasitemia in Giemsa-stained thin blood smears. BMC Cell Biol. 2008;9:15.CrossRef Le M-T, Bretschneider TR, Kuss C, Preiser PR. A novel semi-automatic image processing approach to determine Plasmodium falciparum parasitemia in Giemsa-stained thin blood smears. BMC Cell Biol. 2008;9:15.CrossRef
25.
go back to reference Linder N, Turkki R, Walliander M, Mårtensson A, Diwan V, Rahtu E, et al. A malaria diagnostic tool based on computer vision screening and visualization of Plasmodium falciparum candidate areas in digitized blood smears. PLoS ONE. 2014;9:e104855.CrossRef Linder N, Turkki R, Walliander M, Mårtensson A, Diwan V, Rahtu E, et al. A malaria diagnostic tool based on computer vision screening and visualization of Plasmodium falciparum candidate areas in digitized blood smears. PLoS ONE. 2014;9:e104855.CrossRef
26.
go back to reference Mehanian C, Jaiswal M, Thompson C, Horning M, Ostbye T, McGuire S, et al. Computer-automated malaria diagnosis and quantitation using convolutional neural networks. In: IEEE Int Conf Comput Vis ICCV. 2017;116–25. Mehanian C, Jaiswal M, Thompson C, Horning M, Ostbye T, McGuire S, et al. Computer-automated malaria diagnosis and quantitation using convolutional neural networks. In: IEEE Int Conf Comput Vis ICCV. 2017;116–25.
28.
go back to reference Ministerio de Salud del Perú. Manual de Procedimientos de Laboratorio Para El Diagnóstico de Malaria (MINSA). Lima: Ministerio de Salud del Perú; 2003. Ministerio de Salud del Perú. Manual de Procedimientos de Laboratorio Para El Diagnóstico de Malaria (MINSA). Lima: Ministerio de Salud del Perú; 2003.
29.
go back to reference Mangold KA, Manson RU, Koay ESC, Stephens L, Regner M, Thomson RB, et al. Real-time PCR for detection and identification of Plasmodium spp. J Clin Microbiol. 2005;43:2435–40.CrossRef Mangold KA, Manson RU, Koay ESC, Stephens L, Regner M, Thomson RB, et al. Real-time PCR for detection and identification of Plasmodium spp. J Clin Microbiol. 2005;43:2435–40.CrossRef
33.
go back to reference Alexander N, Schellenberg D, Ngasala B, Petzold M, Drakeley C, Sutherland C. Assessing agreement between malaria slide density readings. Malar J. 2010;9:4.CrossRef Alexander N, Schellenberg D, Ngasala B, Petzold M, Drakeley C, Sutherland C. Assessing agreement between malaria slide density readings. Malar J. 2010;9:4.CrossRef
Metadata
Title
Automated microscopy for routine malaria diagnosis: a field comparison on Giemsa-stained blood films in Peru
Authors
Katherine Torres
Christine M. Bachman
Charles B. Delahunt
Jhonatan Alarcon Baldeon
Freddy Alava
Dionicia Gamboa Vilela
Stephane Proux
Courosh Mehanian
Shawn K. McGuire
Clay M. Thompson
Travis Ostbye
Liming Hu
Mayoore S. Jaiswal
Victoria M. Hunt
David Bell
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Malaria Journal / Issue 1/2018
Electronic ISSN: 1475-2875
DOI
https://doi.org/10.1186/s12936-018-2493-0

Other articles of this Issue 1/2018

Malaria Journal 1/2018 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.