{"doi":"10.1093/cid/ciae608","title":"Community-Based Tuberculosis Isolation Decisions Require Individualization Based on Effectiveness and Duration of Treatment, Community Risks, and Patient Harms","abstract":"To the Editor—We appreciate the commentary by Acuña-Villaorduña et al [1] in response to the National Tuberculosis Coalition of America (NTCA) guidelines, published in Clinical Infectious Diseases and endorsed by the Infectious Diseases Society of America [2]. Importantly, we agree that sputum smear-microscopy does not reliably correlate with infectiousness after effective treatment initiation [3], changing the paradigm for isolation decisions [4]. Acuña-Villaorduña and colleagues actually raise 2 questions. First, what is the duration of effective treatment required for persons with pulmonary tuberculosis (PWTB) to become noninfectious? And second, what is the optimal timing for discontinuing respiratory isolation in PWTB? While these questions are related, they each have a distinct set of considerations. Unfortunately, there are no reliable tests or biomarkers to distinguish between the majority of PWTB who pose limited infectious risk and those associated with superspreading events. The NTCA recommendations regarding infectiousness were grounded in concordant data from studies using a range of experimental and epidemiologic methods, acknowledging limitations in scientific methods and potential for individual variability [3]. Seminal human to guinea pig studies suggest that transmission ceases almost immediately with effective treatment [5, 6]. This observation has been postulated to stem from the rapid decline in bacillary load within the first 2 days of treatment [7, 8], as well as from mycobacterial impairments resulting from antituberculosis therapy [9–12]. Acuña-Villaorduña et al focus on cough aerosol culture positivity as an alternative predictor of household transmission. These data suggest that only a minority (30%–45%) of PWTB with smear-positive disease produce culture-positive cough aerosols (and would be considered infectious by this definition) [9, 13–15]. Among this subgroup, only a fraction (approximately one-third) produce aerosols with >10 colony-forming unit counts, suggesting that isolation interventions may have limited community benefit for a majority of individuals [9, 13–15]. The authors have also previously reported reductions in Mycobacterium tuberculosis aerosol culture positivity after 1–2 days of treatment when comparing treated patients with pretreatment groups [9]. The NTCA guideline group considered the breadth of this data and concluded that those treated for longer durations (ie, >5 days) are expected to be less infectious than those treated for shorter durations (recommendation 3.2), a recommendation we believe is consistent with the assertions of Acuña-Villaorduña et al. Recognizing the limitations of smear microscopy, recommendation 3.3 focuses on the evidence that effective therapy for a minimum threshold of ≥5 days renders most PWTB noninfectious or a with low likelihood of infectiousness, regardless of sputum bacteriologic status during ongoing antituberculosis treatment. Acuña-Villaorduña et al note data indicating that up to a third of persons receiving treatment for >5 days produce culturable cough aerosols; in this subgroup, patients with multidrug-resistant tuberculosis accounted for a higher proportion of those with persistent cough aerosol positivity [13]. Notably, that study was done before Bedaquiline, Pretomanid, Linezolid, Moxifloxacin (BPaL/M) recommendations, and patients were receiving a low number of drugs likely to be effective [13]; emerging data from human–to–guinea pig studies suggest that effective multidrug-resistant tuberculosis treatment, including with BPaL, may rapidly reduce transmission potential [5, 16]. Whether persistent M. tuberculosis viability in aerosol culture after treatment translates reliably to ongoing transmission potential is also unclear and requires additional investigation. Transcriptomic studies demonstrate that gene expression may be rapidly reduced following treatment initiation, highlighting concerns about interpreting viability based on ","journal":"Clinical Infectious Diseases","year":2024,"id":507617,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9565,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":275219,"name":"Ruvandhi R. Nathavitharana","orcid":"0000-0002-3544-5021","position":1,"is_corresponding":false},{"id":867241,"name":"Joseph Burzynski","orcid":"0000-0002-7109-7669","position":2,"is_corresponding":false},{"id":782873,"name":"Maunank Shah","orcid":"0000-0002-0979-2388","position":0,"is_corresponding":true}],"reference_count":20,"raw_metadata":null,"created_at":"2026-07-19T02:11:02.460057Z","pmid":"39686781","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":[]}