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1. Semi-quantitative group testing for efficient and accurate qPCR screening of pathogens with a wide range of loads

   https://doi.org/10.1186/s12859-024-05798-3  

   Nambiar, Ananthan; Pan, Chao; Rana, Vishal; Cheraghchi, Mahdi; Ribeiro, João; Maslov, Sergei; Milenkovic, Olgica (May 2024, BMC Bioinformatics)

   Abstract BackgroundPathogenic infections pose a significant threat to global health, affecting millions of people every year and presenting substantial challenges to healthcare systems worldwide. Efficient and timely testing plays a critical role in disease control and transmission prevention. Group testing is a well-established method for reducing the number of tests needed to screen large populations when the disease prevalence is low. However, it does not fully utilize the quantitative information provided by qPCR methods, nor is it able to accommodate a wide range of pathogen loads. ResultsTo address these issues, we introduce a novel adaptive semi-quantitative group testing (SQGT) scheme to efficiently screen populations via two-stage qPCR testing. The SQGT method quantizes cycle threshold (Ct) values into multiple bins, leveraging the information from the first stage of screening to improve the detection sensitivity. DynamicCtthreshold adjustments mitigate dilution effects and enhance test accuracy. Comparisons with traditional binary outcome GT methods show that SQGT reduces the number of tests by 24% on the only complete real-world qPCR group testing dataset from Israel, while maintaining a negligible false negative rate. ConclusionIn conclusion, our adaptive SQGT approach, utilizing qPCR data and dynamic threshold adjustments, offers a promising solution for efficient population screening. With a reduction in the number of tests and minimal false negatives, SQGT holds potential to enhance disease control and testing strategies on a global scale. 

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2. A robust pooled testing approach to expand COVID-19 screening capacity

   https://doi.org/10.1371/journal.pone.0246285  

   Bish, Douglas R.; Bish, Ebru K.; El-Hajj, Hussein; Aprahamian, Hrayer (February 2021, PLOS ONE)

   Pantea, Casian (Ed.)

   Limited testing capacity for COVID-19 has hampered the pandemic response. Pooling is a testing method wherein samples from specimens (e.g., swabs) from multiple subjects are combined into a pool and screened with a single test. If the pool tests positive, then new samples from the collected specimens are individually tested, while if the pool tests negative, the subjects are classified as negative for the disease. Pooling can substantially expand COVID-19 testing capacity and throughput, without requiring additional resources. We develop a mathematical model to determine the best pool size for different risk groups , based on each group’s estimated COVID-19 prevalence. Our approach takes into consideration the sensitivity and specificity of the test, and a dynamic and uncertain prevalence, and provides a robust pool size for each group. For practical relevance, we also develop a companion COVID-19 pooling design tool (through a spread sheet). To demonstrate the potential value of pooling, we study COVID-19 screening using testing data from Iceland for the period, February-28-2020 to June-14-2020, for subjects stratified into high- and low-risk groups. We implement the robust pooling strategy within a sequential framework, which updates pool sizes each week, for each risk group, based on prior week’s testing data. Robust pooling reduces the number of tests, over individual testing, by 88.5% to 90.2%, and 54.2% to 61.9%, respectively, for the low-risk and high-risk groups (based on test sensitivity values in the range [0.71, 0.98] as reported in the literature). This results in much shorter times, on average, to get the test results compared to individual testing (due to the higher testing throughput), and also allows for expanded screening to cover more individuals. Thus, robust pooling can potentially be a valuable strategy for COVID-19 screening. 

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3. Array testing for multiplex assays

   https://doi.org/10.1093/biostatistics/kxy058  

   Hou, Peijie; Tebbs, Joshua M; Wang, Dewei; McMahan, Christopher S; Bilder, Christopher R (October 2018, Biostatistics)

   null (Ed.)

   Summary Group testing involves pooling individual specimens (e.g., blood, urine, swabs, etc.) and testing the pools for the presence of disease. When the proportion of diseased individuals is small, group testing can greatly reduce the number of tests needed to screen a population. Statistical research in group testing has traditionally focused on applications for a single disease. However, blood service organizations and large-scale disease surveillance programs are increasingly moving towards the use of multiplex assays, which measure multiple disease biomarkers at once. Tebbs and others (2013, Two-stage hierarchical group testing for multiple infections with application to the Infertility Prevention Project. Biometrics69, 1064–1073) and Hou and others (2017, Hierarchical group testing for multiple infections. Biometrics73, 656–665) were the first to examine hierarchical group testing case identification procedures for multiple diseases. In this article, we propose new non-hierarchical procedures which utilize two-dimensional arrays. We derive closed-form expressions for the expected number of tests per individual and classification accuracy probabilities and show that array testing can be more efficient than hierarchical procedures when screening individuals for multiple diseases at once. We illustrate the potential of using array testing in the detection of chlamydia and gonorrhea for a statewide screening program in Iowa. Finally, we describe an R/Shiny application that will help practitioners identify the best multiple-disease case identification algorithm. 

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4. Estimate of undetected severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection in acute-care hospital settings using an individual-based microsimulation model

   https://doi.org/10.1017/ice.2022.174  

   Jones, Kasey; Hadley, Emily; Preiss, Sandy; Lofgren, Eric T.; Rice, Donald P.; Stoner, Marie C.; Rhea, Sarah; Adams, Joëlla W. (September 2022, Infection Control & Hospital Epidemiology)

   Abstract Objective: Current guidance states that asymptomatic screening for severe acute respiratory coronavirus virus 2 (SARS-CoV-2) prior to admission to an acute-care setting is at the facility’s discretion. This study’s objective was to estimate the number of undetected cases of SARS-CoV-2 admitted as inpatients under 4 testing approaches and varying assumptions. Design and setting: Individual-based microsimulation of 104 North Carolina acute-care hospitals Patients: All simulated inpatient admissions to acute-care hospitals from December 15, 2021, to January 13, 2022 [ie, during the SARS-COV-2 ο (omicron) variant surge]. Interventions: We simulated (1) only testing symptomatic patients, (2) 1-stage antigen testing with no confirmatory polymerase chain reaction (PCR) test, (3) 1-stage antigen testing with a confirmatory PCR for negative results, and (4) serial antigen screening (ie, repeat antigen test 2 days after a negative result). Results: Over 1 month, there were 77,980 admissions: 13.7% for COVID-19, 4.3% with but not for COVID-19, and 82.0% for non–COVID-19 indications without current infection. Without asymptomatic screening, 1,089 (credible interval [CI], 946–1,253) total SARS-CoV-2 infections (7.72%) went undetected. With 1-stage antigen screening, 734 (CI, 638–845) asymptomatic infections (67.4%) were detected, with 1,277 false positives. With combined antigen and PCR screening, 1,007 (CI, 875–1,159) asymptomatic infections (92.5%) were detected, with 5,578 false positives. A serial antigen testing policy detected 973 (CI, 845–1,120) asymptomatic infections (89.4%), with 2,529 false positives. Conclusions: Serial antigen testing identified >85% of asymptomatic infections and resulted in fewer false positives with less cost per identified infection compared to combined antigen plus PCR testing. 

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5. Group testing for connected communities

   Nikolopoulos, P; Srinivasavaradhan, Sundara Rajan; Guo, Tao; Fragouli, Christina; Diggavi, Suhas (April 2021, Proceedings of the International Conference on Artificial Intelligence and Statistics (AISTATS))

   In this paper, we propose algorithms that leverage a known community structure to make group testing more efficient. We consider a population organized in disjoint communities: each individual participates in a community, and its infection probability depends on the community (s)he participates in. Use cases include families, students who participate in several classes, and workers who share common spaces. Group testing reduces the number of tests needed to identify the infected individuals by pooling diagnostic samples and testing them together. We show that if we design the testing strategy taking into account the community structure, we can significantly reduce the number of tests needed for adaptive and non-adaptive group testing, and can improve the reliability in cases where tests are noisy. 

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