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+Model
ARTICLE IN PRESS
TRSTMH 1037 1—3
Transactions of the Royal Society of Tropical Medicine and Hygiene (2008) xxx, xxx—xxx 1
available at www.sciencedirect.com
journal homepage: www.elsevierhealth.com/journals/trst
4
5 6
Can the power of mobile phones be used to improve tuberculosis diagnosis in developing countries?
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SHORT COMMUNICATION
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Mirko Zimic a,∗, Jorge Coronel a, Robert H. Gilman a,b,c, Carmen Giannina Luna a, Walter H. Curioso d, David A.J. Moore a,b,c a
15
Received 30 September 2008; received in revised form 14 October 2008; accepted 14 October 2008
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KEYWORDS
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Tuberculosis; Diagnosis; Technology; Telemedicine; Mobile phone; Mycobacteria
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26 27 28 29 30 31
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Summary The low-cost Microscopic Observation Drug Susceptibility (MODS) assay is a non-proprietary test that delivers rapid and accurate diagnosis of tuberculosis (TB) and multidrug-resistant TB. Although methodologically straightforward, implementation is challenging in isolated settings where personnel trained in plate reading are lacking. One affordable strategy to address this shortfall is the use of mobile phones, first to transmit images captured by an inverted microscope to a remote site where pattern recognition is performed by trained personnel, and second to receive the resulting output of this analysis. Such a system could be used for training of laboratory personnel through distance learning, resolution of equivocal appearances and quality assurance. © 2008 Published by Elsevier Ltd on behalf of Royal Society of Tropical Medicine and Hygiene.
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During the last few years, telemedicine with remote image viewing has emerged as a highly valuable and versatile tool, particularly suited to places where local expertise is limited. Of the available approaches for image transmission, the Internet and mobile phone telephony have been successfully used in a number of settings. In particular, mobile
∗
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Laboratorio de Investigación de Enfermedades Infecciosas, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Av. Honorio Delgado 430, San Martín de Porras, Lima 31, Perú b Department of International Health, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe St., Room 5515, Baltimore, MD 21205, USA c Department of Infectious Diseases and Immunity, Imperial College London Wellcome Centre for Clinical Tropical Medicine, Faculty of Medicine (Hammersmith Campus), DuCane Road, London W12 0NN, UK d Facultad de Medicina, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Av. Honorio Delgado 430, San Martín de Porras, Lima 31, Perú
7
Corresponding author. Tel.: +51 1 319 0000x2604; fax: +51 1 483 2942. E-mail address: [email protected] (M. Zimic).
phones have been used for diagnosis, monitoring and medical management of several infectious and non-infectious diseases.1—5 We are evaluating the use of mobile phones as part of an integrated system to facilitate efficient diagnosis of tuberculosis (TB), a disease predominantly affecting developing countries although currently re-emerging in the industrialised world. Among the new tools being developed for the detection of TB and multidrug-resistant (MDR) TB is the low-cost Microscopic Observation Drug Susceptibility (MODS) assay for
0035-9203/$ — see front matter © 2008 Published by Elsevier Ltd on behalf of Royal Society of Tropical Medicine and Hygiene. doi:10.1016/j.trstmh.2008.10.015
Please cite this article in press as: Zimic M, et al. Can the power of mobile phones be used to improve tuberculosis TRSTMH 1037 1—3 diagnosis in developing countries? Trans R Soc Trop Med Hyg (2008), doi:10.1016/j.trstmh.2008.10.015
32 33 34 35 36 37 38 39 40 41 42
+Model
ARTICLE IN PRESS
TRSTMH 1037 1—3
2
50 51 52 53 54 55 56 57 58 59 60
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F) using a 10× objective and 10× eyepiece, with a 4 megapixel digital camera (Olympus C-3030) adapted to the trinocular base. Images of MODS cultures were stored on a 256 Mb SD memory card. The original pictures were captured as PNG files with an average size of 750 kb each. To facilitate telephonic transmission, each image was transformed to a compressed JPG format with an average size of 130 kb. The SD memory card was transferred from the digital camera to a mobile phone (Nokia 6110) with internet connection capability. JPG-compressed images were transmitted and uploaded to an ad hoc web server using the internet WAP protocol for mobile phones. A MODS plate expert reader remotely accessed the server and was able to analyse the images directly from the Internet browser by zooming up to its normal aspect. A scheme of the entire process is depicted in Figure 1. To evaluate the efficacy of the mobile phone/web server system in TB diagnosis, 50 images of MODS cultures containing Mycobacterium tuberculosis, 20 images of MODS cultures of atypical mycobacteria and 5 culture-negative images were obtained using the Nikon system. The atypical mycobacterium included strains of M. avium, M. kansasii and M. chelonae. Mycobacterium bovis strains were also
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45
accurate and fast diagnosis and drug susceptibility determination. This test is based on visual recognition of a characteristic tangling growth pattern of mycobacteria in liquid media observed by inverted microscopy.6,7 Extensive use in developing countries may be limited because pattern recognition requires trained personnel in order to achieve the best sensitivity and specificity. The fundamental basis of the MODS method makes it a suitable candidate for using the power of mobile phones both to transmit images to a remote site for expert analysis and then to receive the telephonically transmitted results of this analysis. To test the potential utility of mobile phones in TB diagnosis, we performed a study in which MODS culture images were transmitted using a mobile phone to a web server. An expert in reading MODS plates accessed and read the images online. The system used to capture MODS images consisted of a commercial inverted light microscope (Nikon Eclipse TS100-
CO RR
44
UN
43
M. Zimic et al.
Figure 1 Diagram of the mobile phone-assisted Microscopic Observation Drug Susceptibility (MODS) pattern recognition system.
Figure 2 (A) Original image (750 kb) obtained by the Olympus digital camera. (B) Image downloaded from the web server after compression and upload using a mobile phone (127 Kb).
Please cite this article in press as: Zimic M, et al. Can the power of mobile phones be used to improve tuberculosis TRSTMH 1037 1—3 diagnosis in developing countries? Trans R Soc Trop Med Hyg (2008), doi:10.1016/j.trstmh.2008.10.015
61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84
+Model
ARTICLE IN PRESS
TRSTMH 1037 1—3
Mobile phones for remote TB diagnosis
92 93 94 95 96 97 98 99 100 101 102 103 104 105
106 107 108 109 110 111
Authors’ contributions: MZ, WC and DAJM developed the concept; MZ, JC, RHG, CGL, WC and DAJM designed the study; JC and CGL read the images that were transmitted by MZ; MZ, JC, RHG, CGL, WC and DAJM all contributed to the writing and editing of the manuscript. All authors read and approved the final version. MZ is guarantor of the paper.
Ethical approval: Not required.
115
References
116
1. Frean J. Microscopic images transmitted by mobile cameraphone. Trans R Soc Trop Med Hyg 2007;101:1053. 2. Blaivas M, Lyon M, Duggal S. Ultrasound image transmission via camera phones for overreading. Am J Emerg Med 2005;23:433—8. 3. Piek J, Hebecker R, Schutze M, Sola S, Mann S, Buchholz K. Image transfer by mobile phones in neurosurgery. Zentralbl Neurochir 2006;67:193—6. 4. Razdan S, Johannes J, Kuo RL, Bagley DH. The camera phone: a novel aid in urologic practice. Urology 2006;67:665—9. 5. Curioso WH, Karras BT, Campos PE, Buendia C, Holmes KK, Kimball AM. Design and implementation of Cell-PREVEN: a real-time surveillance system for adverse events using cell phones in Peru. AMIA Annu Symp Proc 2005:176—80. 6. Caviedes L, Lee TS, Gilman RH, Sheen P, Spellman E, Lee EH, et al. Rapid, efficient detection and drug susceptibility testing of Mycobacterium tuberculosis in sputum by microscopic observation of broth cultures. The Tuberculosis Working Group in Peru. J Clin Microbiol 2000;38:1203—8. 7. Moore DA, Evans CA, Gilman RH, Caviedes L, Coronel J, Vivar A, et al. Microscopic-observation drug-susceptibility assay for the diagnosis of TB. N Engl J Med 2006;355:1539—50.
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Conflicts of interest: None declared.
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112
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88
Funding: This study was funded by a Wellcome Trust Career Development Fellowship awarded to DAJM (078067/Z/05).
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87
included. Images transmitted by mobile phone were blindly read by the expert reader and results were compared with those made at the inverted microscope itself by a laboratory MODS technician. An example of a MODS pattern image transmitted and received by the web server is shown in Figure 2. The concordance of readings between direct observation on the Nikon microscope and the mobile phone-transmitted image was 98.7% (74/75). The single discrepancy corresponded to an atypical mycobacterium that was misclassified as a contaminant after mobile phone transmission. It is important to highlight that for some atypical mycobacteria an important distinguishing characteristic from M. tuberculosis is the presence of small spineshaped surface structures; these are not lost through file compression. In conclusion, we propose that with a relatively minimal investment in mobile phones, it is possible to facilitate the diagnosis of TB and MDR-TB using MODS in remote settings where a lack of trained personnel may otherwise be a limitation.
CO RR
86
UN
85
3
Please cite this article in press as: Zimic M, et al. Can the power of mobile phones be used to improve tuberculosis TRSTMH 1037 1—3 diagnosis in developing countries? Trans R Soc Trop Med Hyg (2008), doi:10.1016/j.trstmh.2008.10.015
113
117 118 119 120 121 122 123 124 125 126 127 128 129 130 131 132 133 134 135 136 137 138
ARTICLE IN PRESS
TRSTMH 1037 1—3
Transactions of the Royal Society of Tropical Medicine and Hygiene (2008) xxx, xxx—xxx 1
available at www.sciencedirect.com
journal homepage: www.elsevierhealth.com/journals/trst
4
5 6
Can the power of mobile phones be used to improve tuberculosis diagnosis in developing countries?
F
3
SHORT COMMUNICATION
OO
2
Mirko Zimic a,∗, Jorge Coronel a, Robert H. Gilman a,b,c, Carmen Giannina Luna a, Walter H. Curioso d, David A.J. Moore a,b,c a
15
Received 30 September 2008; received in revised form 14 October 2008; accepted 14 October 2008
13
ED
12
16
KEYWORDS
17
Tuberculosis; Diagnosis; Technology; Telemedicine; Mobile phone; Mycobacteria
18 19 20 21 22 23 24 25
26 27 28 29 30 31
EC T
11
Summary The low-cost Microscopic Observation Drug Susceptibility (MODS) assay is a non-proprietary test that delivers rapid and accurate diagnosis of tuberculosis (TB) and multidrug-resistant TB. Although methodologically straightforward, implementation is challenging in isolated settings where personnel trained in plate reading are lacking. One affordable strategy to address this shortfall is the use of mobile phones, first to transmit images captured by an inverted microscope to a remote site where pattern recognition is performed by trained personnel, and second to receive the resulting output of this analysis. Such a system could be used for training of laboratory personnel through distance learning, resolution of equivocal appearances and quality assurance. © 2008 Published by Elsevier Ltd on behalf of Royal Society of Tropical Medicine and Hygiene.
CO RR
9 10
During the last few years, telemedicine with remote image viewing has emerged as a highly valuable and versatile tool, particularly suited to places where local expertise is limited. Of the available approaches for image transmission, the Internet and mobile phone telephony have been successfully used in a number of settings. In particular, mobile
∗
UN
8
PR
14
Laboratorio de Investigación de Enfermedades Infecciosas, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Av. Honorio Delgado 430, San Martín de Porras, Lima 31, Perú b Department of International Health, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe St., Room 5515, Baltimore, MD 21205, USA c Department of Infectious Diseases and Immunity, Imperial College London Wellcome Centre for Clinical Tropical Medicine, Faculty of Medicine (Hammersmith Campus), DuCane Road, London W12 0NN, UK d Facultad de Medicina, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Av. Honorio Delgado 430, San Martín de Porras, Lima 31, Perú
7
Corresponding author. Tel.: +51 1 319 0000x2604; fax: +51 1 483 2942. E-mail address: [email protected] (M. Zimic).
phones have been used for diagnosis, monitoring and medical management of several infectious and non-infectious diseases.1—5 We are evaluating the use of mobile phones as part of an integrated system to facilitate efficient diagnosis of tuberculosis (TB), a disease predominantly affecting developing countries although currently re-emerging in the industrialised world. Among the new tools being developed for the detection of TB and multidrug-resistant (MDR) TB is the low-cost Microscopic Observation Drug Susceptibility (MODS) assay for
0035-9203/$ — see front matter © 2008 Published by Elsevier Ltd on behalf of Royal Society of Tropical Medicine and Hygiene. doi:10.1016/j.trstmh.2008.10.015
Please cite this article in press as: Zimic M, et al. Can the power of mobile phones be used to improve tuberculosis TRSTMH 1037 1—3 diagnosis in developing countries? Trans R Soc Trop Med Hyg (2008), doi:10.1016/j.trstmh.2008.10.015
32 33 34 35 36 37 38 39 40 41 42
+Model
ARTICLE IN PRESS
TRSTMH 1037 1—3
2
50 51 52 53 54 55 56 57 58 59 60
F
49
OO
48
PR
47
ED
46
F) using a 10× objective and 10× eyepiece, with a 4 megapixel digital camera (Olympus C-3030) adapted to the trinocular base. Images of MODS cultures were stored on a 256 Mb SD memory card. The original pictures were captured as PNG files with an average size of 750 kb each. To facilitate telephonic transmission, each image was transformed to a compressed JPG format with an average size of 130 kb. The SD memory card was transferred from the digital camera to a mobile phone (Nokia 6110) with internet connection capability. JPG-compressed images were transmitted and uploaded to an ad hoc web server using the internet WAP protocol for mobile phones. A MODS plate expert reader remotely accessed the server and was able to analyse the images directly from the Internet browser by zooming up to its normal aspect. A scheme of the entire process is depicted in Figure 1. To evaluate the efficacy of the mobile phone/web server system in TB diagnosis, 50 images of MODS cultures containing Mycobacterium tuberculosis, 20 images of MODS cultures of atypical mycobacteria and 5 culture-negative images were obtained using the Nikon system. The atypical mycobacterium included strains of M. avium, M. kansasii and M. chelonae. Mycobacterium bovis strains were also
EC T
45
accurate and fast diagnosis and drug susceptibility determination. This test is based on visual recognition of a characteristic tangling growth pattern of mycobacteria in liquid media observed by inverted microscopy.6,7 Extensive use in developing countries may be limited because pattern recognition requires trained personnel in order to achieve the best sensitivity and specificity. The fundamental basis of the MODS method makes it a suitable candidate for using the power of mobile phones both to transmit images to a remote site for expert analysis and then to receive the telephonically transmitted results of this analysis. To test the potential utility of mobile phones in TB diagnosis, we performed a study in which MODS culture images were transmitted using a mobile phone to a web server. An expert in reading MODS plates accessed and read the images online. The system used to capture MODS images consisted of a commercial inverted light microscope (Nikon Eclipse TS100-
CO RR
44
UN
43
M. Zimic et al.
Figure 1 Diagram of the mobile phone-assisted Microscopic Observation Drug Susceptibility (MODS) pattern recognition system.
Figure 2 (A) Original image (750 kb) obtained by the Olympus digital camera. (B) Image downloaded from the web server after compression and upload using a mobile phone (127 Kb).
Please cite this article in press as: Zimic M, et al. Can the power of mobile phones be used to improve tuberculosis TRSTMH 1037 1—3 diagnosis in developing countries? Trans R Soc Trop Med Hyg (2008), doi:10.1016/j.trstmh.2008.10.015
61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84
+Model
ARTICLE IN PRESS
TRSTMH 1037 1—3
Mobile phones for remote TB diagnosis
92 93 94 95 96 97 98 99 100 101 102 103 104 105
106 107 108 109 110 111
Authors’ contributions: MZ, WC and DAJM developed the concept; MZ, JC, RHG, CGL, WC and DAJM designed the study; JC and CGL read the images that were transmitted by MZ; MZ, JC, RHG, CGL, WC and DAJM all contributed to the writing and editing of the manuscript. All authors read and approved the final version. MZ is guarantor of the paper.
Ethical approval: Not required.
115
References
116
1. Frean J. Microscopic images transmitted by mobile cameraphone. Trans R Soc Trop Med Hyg 2007;101:1053. 2. Blaivas M, Lyon M, Duggal S. Ultrasound image transmission via camera phones for overreading. Am J Emerg Med 2005;23:433—8. 3. Piek J, Hebecker R, Schutze M, Sola S, Mann S, Buchholz K. Image transfer by mobile phones in neurosurgery. Zentralbl Neurochir 2006;67:193—6. 4. Razdan S, Johannes J, Kuo RL, Bagley DH. The camera phone: a novel aid in urologic practice. Urology 2006;67:665—9. 5. Curioso WH, Karras BT, Campos PE, Buendia C, Holmes KK, Kimball AM. Design and implementation of Cell-PREVEN: a real-time surveillance system for adverse events using cell phones in Peru. AMIA Annu Symp Proc 2005:176—80. 6. Caviedes L, Lee TS, Gilman RH, Sheen P, Spellman E, Lee EH, et al. Rapid, efficient detection and drug susceptibility testing of Mycobacterium tuberculosis in sputum by microscopic observation of broth cultures. The Tuberculosis Working Group in Peru. J Clin Microbiol 2000;38:1203—8. 7. Moore DA, Evans CA, Gilman RH, Caviedes L, Coronel J, Vivar A, et al. Microscopic-observation drug-susceptibility assay for the diagnosis of TB. N Engl J Med 2006;355:1539—50.
F
91
114
OO
90
Conflicts of interest: None declared.
PR
89
112
ED
88
Funding: This study was funded by a Wellcome Trust Career Development Fellowship awarded to DAJM (078067/Z/05).
EC T
87
included. Images transmitted by mobile phone were blindly read by the expert reader and results were compared with those made at the inverted microscope itself by a laboratory MODS technician. An example of a MODS pattern image transmitted and received by the web server is shown in Figure 2. The concordance of readings between direct observation on the Nikon microscope and the mobile phone-transmitted image was 98.7% (74/75). The single discrepancy corresponded to an atypical mycobacterium that was misclassified as a contaminant after mobile phone transmission. It is important to highlight that for some atypical mycobacteria an important distinguishing characteristic from M. tuberculosis is the presence of small spineshaped surface structures; these are not lost through file compression. In conclusion, we propose that with a relatively minimal investment in mobile phones, it is possible to facilitate the diagnosis of TB and MDR-TB using MODS in remote settings where a lack of trained personnel may otherwise be a limitation.
CO RR
86
UN
85
3
Please cite this article in press as: Zimic M, et al. Can the power of mobile phones be used to improve tuberculosis TRSTMH 1037 1—3 diagnosis in developing countries? Trans R Soc Trop Med Hyg (2008), doi:10.1016/j.trstmh.2008.10.015
113
117 118 119 120 121 122 123 124 125 126 127 128 129 130 131 132 133 134 135 136 137 138
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