The integrated approach of learning tuberculosis transmission within and outside households via random directed graph models

Household contact studies are frequently used in tuberculosis transmission research, and models based on them often focus on transmission within the household. This contradicts recent research which suggests the transmission may be more likely to happen outside the household than within the household in high burden settings where these studies are frequently conducted. Consequently, most models would lead to biased estimates and misleading public health interventions. There is a strong need for developing models that allow concurrent estimation of household and extra-household transmission. In this study, we develop a random directed graph model for tuberculosis transmission, which permits users to concurrently build models for both household and extra-household transmission. Furthermore, our model can estimate the relative frequency of household transmission versus extra-household transmission and consistently produce unbiased estimates for risk factors, regardless of whether community controls are available. We illustrate our approach with a household contact study conducted in Vitória, Brazil, and our results indicate that extra-household transmission can account for 63% to 98% of M. tuberculosis infections detected during such a study. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial This is a household contact study, not clinical trial ### Funding Statement This work was funded by NIH R01 GM122876. The funding body had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by the Comite de Etica em Pesquisa do Centro de Ciencias da Saude, Universidade Federal do Espirito Santo, the Comissao Nacional de Etica em Pesquisa, and the Institutional Review Board of Boston University Medical Center and Rutgers New Jersey Medical School, Rutgers University (formerly University of Medicine and Dentistry of New Jersey). We obtained written informed consent and assent in Portuguese according to the age-specific guidelines of participating institutions. All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data used in this manuscript is available online.