Abstract
In infectious disease diagnosis, results need to be communicated rapidly to healthcare professionals once testing has been completed so that care pathways can be implemented. This represents a particular challenge when testing in remote, low-resource rural communities, in which such diseases often create the largest burden. Here, we report a smartphone-based end-to-end platform for multiplexed DNA diagnosis of malaria. The approach uses a low-cost paper-based microfluidic diagnostic test, which is combined with deep learning algorithms for local decision support and blockchain technology for secure data connectivity and management. We validated the approach via field tests in rural Uganda, where it correctly identified more than 98% of tested cases. Our platform also provides secure geotagged diagnostic information, which creates the possibility of integrating infectious disease data within surveillance frameworks.
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Data availability
The data that support the findings of this study for Figs. 3 and 5 are available in the University of Glasgow’s Enlighten repository with the identifier https://doi.org/10.5525/gla.researchdata.1106.
Code availability
The code for the Android app, the CNN and blockchain architecture is available through an open Zenodo repository (https://doi.org/10.5281/zenodo.4429293), which includes a GitHub repository for the code (https://github.com/XGuoo/BlockchainDiagnostics), and is licensed under an Open Source GNU GPLv3 Licence. The repository README.md markdown file describes the dataset and includes installation and demo instructions.
References
World Malaria Report 2019 (WHO, 2019); https://www.who.int/news-room/feature-stories/detail/world-malaria-report-2019
Mabey, D., Peeling, R. W., Ustianowski, A. & Perkins, M. D. Diagnostics for the developing world. Nat. Rev. Microbiol. 2, 231–240 (2004).
The Roll Back Malaria Strategy for Improving Access to Treatment Through Home Management of Malaria (archived) (WHO, 2014); https://apps.who.int/iris/handle/10665/69057
Yukich, J. O. et al. A description of malaria sentinel surveillance: a case study in Oromia Regional State, Ethiopia. Malar. J. 13, 88 (2014).
Wood, C. S. et al. Taking connected mobile-health diagnostics of infectious diseases to the field. Nature 566, 467–474 (2019).
Alabdulatif, A., Khalil, I., Forkan, A. R. M. & Atiquzzaman, M. Real-time secure health surveillance for smarter health communities. IEEE Commun. Mag. 57, 122–129 (2019).
Xu, H. et al. BeepTrace: blockchain-enabled privacy-preserving contact tracing for COVID-19 pandemic and beyond. IEEE Internet Things J . 8, 3915–3929 (2021).
Holst, C. et al. Sub-Saharan Africa—the new breeding ground for global digital health. Lancet Digit. Health 2, e160–e162 (2020).
Bastawrous, A. Increasing access to eye care. There’s an app for that. Peek: smartphone technology for eye health. Int. J. Epidemiol. 45, 1040–1043 (2016).
Scherr, T. F., Gupta, S., Wright, D. W. & Haselton, F. R. Mobile phone imaging and cloud-based analysis for standardized malaria detection and reporting. Sci. Rep. 6, 28645 (2016).
Wanja, E. W. et al. Field evaluation of diagnostic performance of malaria rapid diagnostic tests in western Kenya. Malar. J. 15, 456 (2016).
Response Plan to pfhrp2 Gene Deletions Global Malaria Programme (WHO, 2019).
Nolder, D. et al. Failure of rapid diagnostic tests in Plasmodium falciparum malaria cases in UK travellers: identification and characterisation of the parasites. Int. J. Infect. Dis. https://doi.org/10.1016/j.ijid.2021.05.008 (2021).
Grignard, L. et al. A novel multiplex qPCR assay for detection of Plasmodium falciparum with histidine-rich protein 2 and 3 (pfhrp2 and pfhrp3) deletions in polyclonal infections. EBioMedicine 55, 102757 (2020).
Kreidenweiss, A. et al. Monitoring the threatened utility of malaria rapid diagnostic tests by novel high-throughput detection of Plasmodium falciparum hrp2 and hrp3 deletions: a cross-sectional, diagnostic accuracy study. EBioMedicine 50, 14–22 (2019).
Esposito, C., De Santis, A., Tortora, G., Chang, H. & Choo, K. K. R. Blockchain: a panacea for healthcare cloud-based data security and privacy? IEEE Cloud Comput. 5, 31–37 (2018).
Perakslis, E. D. Using digital health to enable ethical health research in conflict and other humanitarian settings. Confl. Health 12, 23 (2018).
Farouk, A., Alahmadi, A., Ghose, S. & Mashatan, A. Blockchain platform for industrial healthcare: vision and future opportunities. Comput. Commun. 154, 223–235 (2020).
Cheng, X., Chen, F., Xie, D., Sun, H. & Huang, C. Design of a secure medical data sharing scheme based on blockchain. J. Med. Syst. 44, 52 (2020).
Vazirani, A. A., O’Donoghue, O., Brindley, D. & Meinert, E. Blockchain vehicles for efficient medical records management. npj Digit. Med. 3, 1 (2020).
Reboud, J. et al. Paper-based microfluidics for DNA diagnostics of malaria in low resource underserved rural communities. Proc. Natl Acad. Sci. USA 116, 4834–4842 (2019).
Authorizing OAuth Apps. GitHub Developer Guide (GitHub); https://developer.github.com/apps/building-oauth-apps/authorizing-oauth-apps/
Dehnavieh, R. et al. The District Health Information System (DHIS2): a literature review and meta-synthesis of its strengths and operational challenges based on the experiences of 11 countries. Health Inf. Manag. J. 48, 62–75 (2019).
Vourganas, I., Stankovic, V. & Stankovic, L. Individualised responsible artificial intelligence for home-based rehabilitation. Sensors 21, 2 (2020).
Smartphone Users Worldwide (Statista, 2020); https://www.statista.com/statistics/330695/number-of-smartphone-users-worldwide/
Okeleke, K. Uganda: Driving Inclusive Socio-Economic Progress Through Mobile-Enabled Digital Transformation (GSM Association, 2019); https://www.gsma.com/mobilefordevelopment/wp-content/uploads/2019/03/Uganda-Report-Driving-inclusive-socio-economic-progress-through-mobile-enabled-digital-transformation.pdf
Scherr, T. F., Moore, C. P., Thuma, P. & Wright, D. W. Evaluating network readiness for mHealth interventions using the Beacon mobile phone app: application development and validation study. JMIR mHealth uHealth 8, e18413 (2020).
Kumar, S., Srivastava, R., Pathak, S. & Kumar, B. in Intelligent Data Security Solutions for e-Health Applications (eds Singh, A. K. & Elhoseny, M.) 219–235 (Elsevier, 2020).
Zhong, B. et al. A comparative study of image classification algorithms for Foraminifera identification. In Proc. 2017 IEEE Symposium Series on Computational Intelligence (SSCI) 1–8 (IEEE, 2017); https://doi.org/10.1109/SSCI.2017.8285164
Wang, P., Fan, E. & Wang, P. Comparative analysis of image classification algorithms based on traditional machine learning and deep learning. Pattern Recognit. Lett. 141, 61–67 (2021).
Wang, L. et al. Comparative analysis of image classification methods for automatic diagnosis of ophthalmic images. Sci. Rep. 7, 41545 (2017).
O’Mahony, N. et al. Deep learning vs. traditional computer vision. In Advances in Computer Vision CVC 2019 Advances in Intelligent Systems and Computing (eds Arai, K. & Kapoor, S.) Vol. 943 https://doi.org/10.1007/978-3-030-17795-9_10 (Springer, 2019).
Jaigirdar, F. T., Rudolph, C. & Bain, C. Can I trust the data I see?: a physician’s concern on medical data in IoT health architectures. In Proc. Australasian Computer Science Week Multiconference Article no. 27, 1–10 (ACM, 2019); https://doi.org/10.1145/3290688.3290731
Cheng, M., Nazarian, S. & Bogdan, P. There is hope after all: quantifying opinion and trustworthiness in neural networks. Front. Artif. Intell. 3, 54 (2020).
Cammarota, R. et al. Trustworthy AI inference systems: an industry research view. Preprint at https://arxiv.org/abs/2008.04449 (2020).
Recommendations on Digital Interventions for Health System Strengthening (WHO, 2019).
Global Strategy on Digital Health 2020–2025 (WHO, 2021); https://cdn.who.int/media/docs/default-source/documents/gs4dhdaa2a9f352b0445bafbc79ca799dce4d.pdf
General Data Protection Regulation (GDPR)—Official Legal Text (European Parliament and Council of the European Union, 2018); https://gdpr-info.eu/
Acharya, J., Bonawitz, K., Kairouz, P., Ramage, D. & Sun, Z. Context-aware local differential privacy. In Proc. 37th International Conference on Machine Learning Vol. 119, 52–62 (PMLR, 2020).
Sun, T. Q. & Medaglia, R. Mapping the challenges of artificial intelligence in the public sector: evidence from public healthcare. Gov. Inf. Q. 36, 368–383 (2019).
Díez, J., Pérez-Núñez, P., Luaces, O., Remeseiro, B. & Bahamonde, A. Towards explainable personalized recommendations by learning from users’ photos. Inf. Sci. 520, 416–430 (2020).
Notomi, T. et al. Loop-mediated isothermal amplification of DNA. Nucleic Acids Res. 28, 63 (2000).
Chollet, F. The sequential model (Keras); https://keras.io/guides/sequential_model/
TensorFlow Lite. ML for mobile and edge devices (TensorFlow); https://www.tensorflow.org/lite
Shabbeer Basha, S. H., Ram Dubey, S., Pulabaigari, V. & Mukherjee, S. Impact of fully connected layers on performance of convolutional neural networks for image classification. Neurocomputing 378, 112–119 (2019).
Acknowledgements
We thank P. Lamberton for help with ethical clearance and facilitation, Epigem Ltd for help with device manufacturing, E. O’Shaughnessy for device assembly, O. Tufayl for initial app GUI development, as well as A. Atuhire for sampling and treatment in the field in Uganda. The study was supported by the UK Global Challenges Research Fund, the Scottish Funding Council and the Engineering and Physical Sciences Research Council (EPSRC) Institutional Support Fund (grant no. EP/R512813/1), as well as by EPSRC EP/R01437X/1, also supported by the National Institute for Health Research and EP/T029765/1. A.G. acknowledges support from EPSRC studentship EP/N509668/1.
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X.G. and M.A.K. developed and implemented the decision support system and, with I.D., implemented it on mobile platforms. M.A.K., A.G., S.K. and X.Y. performed experiments in the laboratory in Glasgow. A.G., M.A.K., M.A., J.R., E.M.T. and J.M.C. designed the field study. M.A.K., A.G., C.R., D.A., J.R. and J.M.C. carried out the field study. X.G., A.L.M., J.R. and J.M.C. analysed the data and wrote the manuscript. All authors edited the manuscript.
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Supplementary Information
Supplementary methods, Figs. 1–7 and Tables 1–4.
Supplementary Video 1
App usage demonstration.
Supplementary Data 1
Tabulated field test results. Notation: TP, true positive (positive for PCR and for origami test); TN, true negative (negative for PCR and origami test); FN, false negative (negative for origami test but positive for PCR); FP, false positive (positive for origami test but negative for PCR). Real-time PCR Ct values are obtained in triplicate. It is important to note that the prevalence of the disease is extremely high in the area studied. In this situation, where the existing field tests have lower sensitivity, and where we cannot return for treatment, after confirmatory, more sensitive, gold-standard PCR analysis (performed retrospectively in Glasgow), the ethical protocol advises to treat on a ‘presumed positive’ basis.
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Guo, X., Khalid, M.A., Domingos, I. et al. Smartphone-based DNA diagnostics for malaria detection using deep learning for local decision support and blockchain technology for security. Nat Electron 4, 615–624 (2021). https://doi.org/10.1038/s41928-021-00612-x
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DOI: https://doi.org/10.1038/s41928-021-00612-x