Estimating the prevalence of two or more diseases using outcomes from multiplex group testing.

When screening a population for infectious diseases, pooling individual specimens (e.g., blood, swabs, urine, etc.) can provide enormous cost savings when compared to testing specimens individually. In the biostatistics literature, testing pools of specimens is commonly known as group testing or pooled testing. Although estimating a population-level prevalence with group testing data has received a large amount of attention, most of this work has focused on applications involving a single disease, such as human immunodeficiency virus. Modern methods of screening now involve testing pools and individuals for multiple diseases simultaneously through the use of multiplex assays. Hou et al. (2017, Biometrics, 73, 656-665) and Hou et al. (2020, Biostatistics, 21, 417-431) recently proposed group testing protocols for multiplex assays and derived relevant case identification characteristics, including the expected number of tests and those which quantify classification accuracy. In this article, we describe Bayesian methods to estimate population-level disease probabilities from implementing these protocols or any other multiplex group testing protocol which might be carried out in practice. Our estimation methods can be used with multiplex assays for two or more diseases while incorporating the possibility of test misclassification for each disease. We use chlamydia and gonorrhea testing data collected at the State Hygienic Laboratory at the University of Iowa to illustrate our work. We also provide an online R resource practitioners can use to implement the methods in this article.

Optimizing Pooled Testing for Estimating the Prevalence of Multiple Diseases.

Pooled testing can enhance the efficiency of diagnosing individuals with diseases of low prevalence. Often, pooling is implemented using standard groupings (2, 5, 10, etc.). On the other hand, optimization theory can provide specific guidelines in finding the ideal pool size and pooling strategy. This article focuses on optimizing the precision of disease prevalence estimators calculated from multiplex pooled testing data. In the context of a surveillance application of animal diseases, we study the estimation efficiency (i.e., precision) and cost efficiency of the estimators with adjustments for the number of expended tests. This enables us to determine the pooling strategies that offer the highest benefits when jointly estimating the prevalence of multiple diseases, such as theileriosis and anaplasmosis. The outcomes of our work can be used in designing pooled testing protocols, not only in simple pooling scenarios but also in more complex scenarios where individual retesting is performed in order to identify positive cases. A software application using the shiny package in R is provided with this article to facilitate implementation of our methods. Supplementary materials accompanying this paper appear online. Supplementary materials for this article are available at 10.1007/s13253-022-00511-4.

Group testing regression models with dilution submodels.

Group testing, where specimens are tested initially in pools, is widely used to screen individuals for sexually transmitted diseases. However, a common problem encountered in practice is that group testing can increase the number of false negative test results. This occurs primarily when positive individual specimens within a pool are diluted by negative ones, resulting in positive pools testing negatively. If the goal is to estimate a population-level regression model relating individual disease status to observed covariates, severe bias can result if an adjustment for dilution is not made. Recognizing this as a critical issue, recent binary regression approaches in group testing have utilized continuous biomarker information to acknowledge the effect of dilution. In this paper, we have the same overall goal but take a different approach. We augment existing group testing regression models (that assume no dilution) with a parametric dilution submodel for pool-level sensitivity and estimate all parameters using maximum likelihood. An advantage of our approach is that it does not rely on external biomarker test data, which may not be available in surveillance studies. Furthermore, unlike previous approaches, our framework allows one to formally test whether dilution is present based on the observed group testing data. We use simulation to illustrate the performance of our estimation and inference methods, and we apply these methods to 2 infectious disease data sets.

Estimating the prevalence of multiple diseases from two-stage hierarchical pooling.

Testing protocols in large-scale sexually transmitted disease screening applications often involve pooling biospecimens (e.g., blood, urine, and swabs) to lower costs and to increase the number of individuals who can be tested. With the recent development of assays that detect multiple diseases, it is now common to test biospecimen pools for multiple infections simultaneously. Recent work has developed an expectation-maximization algorithm to estimate the prevalence of two infections using a two-stage, Dorfman-type testing algorithm motivated by current screening practices for chlamydia and gonorrhea in the USA. In this article, we have the same goal but instead take a more flexible Bayesian approach. Doing so allows us to incorporate information about assay uncertainty during the testing process, which involves testing both pools and individuals, and also to update information as individuals are tested. Overall, our approach provides reliable inference for disease probabilities and accurately estimates assay sensitivity and specificity even when little or no information is provided in the prior distributions. We illustrate the performance of our estimation methods using simulation and by applying them to chlamydia and gonorrhea data collected in Nebraska. Copyright © 2016 John Wiley & Sons, Ltd.