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      Kankanet: An artificial neural network-based object detection smartphone application and mobile microscope as a point-of-care diagnostic aid for soil-transmitted helminthiases

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          Abstract

          Background

          Endemic areas for soil-transmitted helminthiases often lack the tools and trained personnel necessary for point-of-care diagnosis. This study pilots the use of smartphone microscopy and an artificial neural network-based (ANN) object detection application named Kankanet to address those two needs.

          Methodology/Principal findings

          A smartphone was equipped with a USB Video Class (UVC) microscope attachment and Kankanet, which was trained to recognize eggs of Ascaris lumbricoides, Trichuris trichiura, and hookworm using a dataset of 2,078 images. It was evaluated for interpretive accuracy based on 185 new images. Fecal samples were processed using Kato-Katz (KK), spontaneous sedimentation technique in tube (SSTT), and Merthiolate-Iodine-Formaldehyde (MIF) techniques. UVC imaging and ANN interpretation of these slides was compared to parasitologist interpretation of standard microscopy.Relative to a gold standard defined as any positive result from parasitologist reading of KK, SSTT, and MIF preparations through standard microscopy, parasitologists reading UVC imaging of SSTT achieved a comparable sensitivity (82.9%) and specificity (97.1%) in A. lumbricoides to standard KK interpretation (97.0% sensitivity, 96.0% specificity). The UVC could not accurately image T. trichiura or hookworm. Though Kankanet interpretation was not quite as sensitive as parasitologist interpretation, it still achieved high sensitivity for A. lumbricoides and hookworm (69.6% and 71.4%, respectively). Kankanet showed high sensitivity for T. trichiura in microscope images (100.0%), but low in UVC images (50.0%).

          Conclusions/Significance

          The UVC achieved comparable sensitivity to standard microscopy with only A. lumbricoides. With further improvement of image resolution and magnification, UVC shows promise as a point-of-care imaging tool. In addition to smartphone microscopy, ANN-based object detection can be developed as a diagnostic aid. Though trained with a limited dataset, Kankanet accurately interprets both standard microscope and low-quality UVC images. Kankanet may achieve sensitivity comparable to parasitologists with continued expansion of the image database and improvement of machine learning technology.

          Author summary

          For rainforest-enshrouded rural villages of Madagascar, soil-transmitted helminthiases are more the rule than the exception. However, the microscopy equipment and lab technicians needed for diagnosis are a distance of several days’ hike away. We piloted a solution for these communities by leveraging resources the villages already had: a traveling team of local health care workers, and their personal Android smartphones. We demonstrated that an inexpensive, commercially available microscope attachment for smartphones could rival the sensitivity and specificity of a regular microscope using standard field fecal sample processing techniques. We also developed an artificial neural network-based object detection Android application, called Kankanet, based on open-source programming libraries. Kankanet was used to detect eggs of the three most common soil-transmitted helminths: Ascaris lumbricoides, Trichuris trichiura, and hookworm. We found Kankanet to be moderately sensitive and highly specific for both standard microscope images and low-quality smartphone microscope images. This proof-of-concept study demonstrates the diagnostic capabilities of artificial neural network-based object detection systems. Since the programming frameworks used were all open-source and user-friendly even for computer science laymen, artificial neural network-based object detection shows strong potential for development of low-cost, high-impact diagnostic aids essential to health care and field research in resource-limited communities.

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          Most cited references25

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          Control of neglected tropical diseases.

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            Estimating the sensitivity and specificity of Kato-Katz stool examination technique for detection of hookworms, Ascaris lumbricoides and Trichuris trichiura infections in humans in the absence of a 'gold standard'.

            The accuracy of the Kato-Katz technique in identifying individuals with soil-transmitted helminth (STH) infections is limited by day-to-day variation in helminth egg excretion, confusion with other parasites and the laboratory technicians' experience. We aimed to estimate the sensitivity and specificity of the Kato-Katz technique to detect infection with Ascaris lumbricoides, hookworm and Trichuris trichiura using a Bayesian approach in the absence of a 'gold standard'. Data were obtained from a longitudinal study conducted between January 2004 and December 2005 in Samar Province, the Philippines. Each participant provided between one and three stool samples over consecutive days. Stool samples were examined using the Kato-Katz technique and reported as positive or negative for STHs. In the presence of measurement error, the true status of each individual is considered as latent data. Using a Bayesian method, we calculated marginal posterior densities of sensitivity and specificity parameters from the product of the likelihood function of observed and latent data. A uniform prior distribution was used (beta distribution: alpha=1, beta=1). A total of 5624 individuals provided at least one stool sample. One, two and three stool samples were provided by 1582, 1893 and 2149 individuals, respectively. All STHs showed variation in test results from day to day. Sensitivity estimates of the Kato-Katz technique for one stool sample were 96.9% (95% Bayesian Credible Interval [BCI]: 96.1%, 97.6%), 65.2% (60.0%, 69.8%) and 91.4% (90.5%, 92.3%), for A. lumbricoides, hookworm and T. trichiura, respectively. Specificity estimates for one stool sample were 96.1% (95.5%, 96.7%), 93.8% (92.4%, 95.4%) and 94.4% (93.2%, 95.5%), for A. lumbricoides, hookworm and T. trichiura, respectively. Our results show that the Kato-Katz technique can perform with reasonable accuracy with one day's stool collection for A. lumbricoides and T. trichiura. Low sensitivity of the Kato-Katz for detection of hookworm infection may be related to rapid degeneration of delicate hookworm eggs with time. (c) 2009 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.
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              “Test and not treat” for onchocerciasis control in a Loa loa endemic area

              Background Implementation of ivermectin-based community treatment for onchocerciasis or lymphatic filariasis elimination has been delayed in Central Africa because of severe adverse events (SAEs), including death, in people with high levels of circulating Loa loa microfilariae (mf). LoaScope, a rapid field-friendly diagnostic tool to quantify L. loa mf in peripheral blood, permits point-of-care identification of individuals “at risk” for SAEs. Methods A “Test and not Treat” (TaNT) strategy was used to implement ivermectin treatment in the Okola health district in Cameroon, where ivermectin distribution was halted in 1999 after the occurrence of fatal Loa-related SAEs. The LoaScope was used to identify and exclude individuals with >20,000 mf per milliliter of blood (at-risk for SAEs) from ivermectin treatment. Active surveillance for post-treatment adverse events (AEs) was conducted daily for 7 days. Results Between August and October 2015, 16,259 (71.1%) individuals >=5 years of age were tested out of a target population of ~22,800. Among the ivermectin-eligible population, 15,522 (95.5%) received ivermectin; 340 (2.1%) were excluded from ivermectin treatment because of a L. loa density above the risk-threshold and 397 (2.4%) were excluded for pregnancy or illness. No SAEs were observed. Non-severe AEs were recorded in 934 individuals, most (67%) of whom had no detectable L. loa mf. Conclusions The LoaScope-based TaNT strategy permitted safe re-implementation of community-wide ivermectin distribution in a heretofore ‘off limits’ health district in Cameroon and is an extremely promising and practical approach for large-scale ivermectin treatment for lymphatic filariasis and onchocerciasis elimination in Loa loa-endemic areas.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SoftwareRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Methodology
                Role: Funding acquisitionRole: InvestigationRole: Methodology
                Role: Funding acquisitionRole: InvestigationRole: Methodology
                Role: ConceptualizationRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: Writing – review & editing
                Role: Data curationRole: MethodologyRole: Project administrationRole: ResourcesRole: ValidationRole: Writing – review & editing
                Role: Data curationRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: Validation
                Role: MethodologyRole: ResourcesRole: SoftwareRole: Writing – review & editing
                Role: Project administrationRole: ResourcesRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: InvestigationRole: MethodologyRole: Project administrationRole: SupervisionRole: ValidationRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS Negl Trop Dis
                PLoS Negl Trop Dis
                plos
                plosntds
                PLoS Neglected Tropical Diseases
                Public Library of Science (San Francisco, CA USA )
                1935-2727
                1935-2735
                5 August 2019
                August 2019
                : 13
                : 8
                : e0007577
                Affiliations
                [1 ] School of Medicine, Stony Brook University, Stony Brook, New York, United States of America
                [2 ] Global Health Institute, Stony Brook University, Stony Brook, New York, United States of America
                [3 ] Immunopathology axis, Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montréal, Québec, Canada
                [4 ] Mycobacteria Unit, Institut Pasteur de Madagascar, Antananarivo, Madagascar
                [5 ] Helminthiasis Unit, Institut Pasteur de Madagascar, Antananarivo, Madagascar
                [6 ] Department of Information Technology, Uppsala University, Uppsala, Sweden
                [7 ] Immunology of Infectious Diseases Unit, Institut Pasteur de Madagascar, Antananarivo, Madagascar
                [8 ] Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, Switzerland
                [9 ] Department of Medicine, Stony Brook University, New York, United States of America
                National Institutes of Allergy and Infectious Diseases, NIH, UNITED STATES
                Author notes

                The authors have declared that no competing interests exist.

                Author information
                https://orcid.org/http://orcid.org/0000-0003-3993-6087
                https://orcid.org/http://orcid.org/0000-0002-2726-1900
                Article
                PNTD-D-19-00063
                10.1371/journal.pntd.0007577
                6695198
                31381573
                31eddf12-ea83-4bba-94cf-98280d31fd83
                © 2019 Yang et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 25 January 2019
                : 25 June 2019
                Page count
                Figures: 5, Tables: 7, Pages: 16
                Product
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/100007261, New York Academy of Medicine;
                Award ID: 2018 Rogers Award
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100001949, American Society of Tropical Medicine and Hygiene;
                Award ID: Benjamin H Kean Travel Fellowship
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100006292, Infectious Diseases Society of America;
                Award ID: 2018 Medical Scholars Program
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100007259, Stony Brook University;
                Award ID: International Research Fellowship
                Award Recipient :
                AY received the David E Rogers Student Fellowship Award (New York Academy of Medicine; https://nyam.org/), the Benjamin H. Kean Travel Fellowship (American Society of Tropical Medicine and Hygiene; https://www.astmh.org/), the Medical Scholars Program (Infectious Diseases Society of America; https://www.idsociety.org/), and International Research Fellowship (Stony Brook University; https://renaissance.stonybrookmedicine.edu/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Organisms
                Eukaryota
                Animals
                Invertebrates
                Helminths
                Ascaris Lumbricoides
                Biology and Life Sciences
                Organisms
                Eukaryota
                Animals
                Invertebrates
                Nematoda
                Ascaris
                Ascaris Lumbricoides
                Biology and Life Sciences
                Organisms
                Eukaryota
                Animals
                Invertebrates
                Helminths
                Hookworms
                Engineering and Technology
                Equipment
                Communication Equipment
                Cell Phones
                Medicine and Health Sciences
                Parasitic Diseases
                Helminth Infections
                Soil-Transmitted Helminthiases
                Medicine and Health Sciences
                Tropical Diseases
                Neglected Tropical Diseases
                Soil-Transmitted Helminthiases
                Medicine and Health Sciences
                Pharmaceutics
                Drug Therapy
                Drug Administration
                Computer and Information Sciences
                Artificial Intelligence
                Artificial Neural Networks
                Biology and Life Sciences
                Computational Biology
                Computational Neuroscience
                Artificial Neural Networks
                Biology and Life Sciences
                Neuroscience
                Computational Neuroscience
                Artificial Neural Networks
                Engineering and Technology
                Equipment
                People and Places
                Geographical Locations
                Africa
                Madagascar
                Custom metadata
                vor-update-to-uncorrected-proof
                2019-08-15
                All data files and artificial neural network training hyperparameters file are available from the OSF database at the following hyperlink: https://osf.io/743eq/?view_only=c7ae2b5273b44724a80b44fb48ed87d1

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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