Development and Validation of a Questionnaire‐Based Model for Households With Multiple <i>Helicobacter pylori</i> Infections: A Family‐Based Screening Strategy

ABSTRACT Helicobacter pylori ( H. pylori ) infections are known to cluster within households. To improve the efficiency of population‐wide H. pylori screening, we therefore developed and validated a questionnaire‐based model to identify households with multiple infections. This model was developed in 2021 based on 10,735 households (31,098 individuals) enrolled from 29 of 31 provinces in mainland China. In 2025, 724 households (2094 individuals) were prospectively enrolled from 3 provinces in China to validate the model. High‐risk households were defined as those containing at least two infected members. After feature selection, we compared 10 machine‐learning classifiers and interpreted the final model using Shapley Additive Explanations (SHAP). The screening efficiency of two different strategies, the screen‐and‐treat strategy (screen all) and the family strategy (screen members in high‐risk households while excluding low‐risk households), was compared in a micro‐simulation of a city of 1,000,000 residents and in an empirical evaluation using real‐world data from 29 provinces. XGBoost achieved the optimal discrimination with an area under the curve (AUC) of 0.861 in the training cohort and 0.839 in the external validation cohort, with corresponding sensitivities of 0.798 and 0.813. In the micro‐simulation, the family strategy identified 276,384 infections with 394,913 tests, whereas the traditional screen‐and‐treat strategy required approximately 680,000 tests to achieve a comparable yield. In the real‐world dataset validation, the family strategy improved detection efficiency from 40.7% to 70.0%, with consistently larger gains in lower‐prevalence provinces. By using a questionnaire‐based model, the family‐based strategy significantly improved screening efficiency and precision in the evaluated datasets, suggesting its potential as a practical tool for household risk stratification and a more efficient H. pylori screening. Further validation is needed in broader geographic and epidemiological settings before wider implementation.