{"doi":"10.1101/2023.02.06.23285528","title":"Trials underestimate the impact of preventive treatment for household contacts exposed to multidrug-resistant tuberculosis: a simulation study","abstract":"Background: Several clinical trials of tuberculosis preventive treatment (TPT) for household contacts of patients with multidrug-resistant tuberculosis (MDR-TB) are nearing completion. The potential benefits of TPT for MDR-TB contacts extend beyond the outcomes that clinical trials can measure. Methods: We developed an agent-based, household-structured TB and MDR-TB transmission model, calibrated to an illustrative setting in India, the country accounting for 26% of global MDR-TB burden. We simulated household contact investigation for contacts of patients with MDR-TB, comparing an MDR-TPT regimen against alternatives of isoniazid preventive treatment, household contact investigation without TPT, or no household contact intervention. We simulated outcomes of a clinical trial and estimated the patient-level and population-level effects over a longer time horizon. Findings: During two years of follow-up per recipient, a simulated 6-month MDR-TPT regimen with 70% efficacy against both DS- and MDR-TB infection could prevent 72% [Interquartile range (IQR): 45 - 100%] of incident MDR-TB among TPT recipients (number needed to treat (NNT) 73 [44 - 176] to prevent one MDR-TB case), compared to household contact investigation without TPT. This NNT decreased to 54 [30 - 183] when median follow-up was increased from two to 16 years, to 27 [11 - Inf] when downstream transmission effects were also considered, and to 12 [8 - 22] when these effects were compared to a scenario of no household contact intervention. Interpretation: If forthcoming trial results demonstrate efficacy, the long-term population impact of MDR-TPT implementation could be much greater than suggested by trial outcomes alone. Funding: NIH K01AI138853 and K08AI127908; Johns Hopkins Catalyst Award.","journal":"medRxiv","year":2023,"id":398421,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9477,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1124990,"name":"Jeff Pennington","orcid":null,"position":1,"is_corresponding":false},{"id":326405,"name":"Amita Gupta","orcid":"0000-0001-7036-2718","position":2,"is_corresponding":false},{"id":315468,"name":"David W. Dowdy","orcid":"0000-0003-0481-7475","position":3,"is_corresponding":false},{"id":315461,"name":"Emily A. Kendall","orcid":"0000-0002-0083-422X","position":4,"is_corresponding":false},{"id":413290,"name":"Parastu Kasaie","orcid":"0000-0002-3744-9501","position":0,"is_corresponding":true}],"reference_count":36,"raw_metadata":null,"created_at":"2026-07-19T01:19:47.744358Z","pmid":"36798407","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}