RESUMO
Household contact studies of tuberculosis (TB) are a common way to study disease transmission dynamics. However these studies lack a mechanism for accounting for community transmission, which is known to be significant, particularly in high burden settings. We illustrate a statistical approach for estimating both the correlates with transmission of TB in a household setting and the probability of community transmission using a modified Bayesian mixed-effects model. This is applied to two household contact studies in Vitória, Brazil from 2008-2013 and Kampala, Uganda from 1995-2004 that enrolled households with an individual that was recently diagnosed with pulmonary TB. We estimate the probability of community transmission to be higher in Uganda (ranging from 0.21 to 0.69, depending on HHC age and HIV status of the index case) than in Brazil (ranging from 0.13 for young children to 0.50 in adults). These estimates are consistent with a higher overall burden of disease in Uganda compared to Brazil. Our method also estimates an increasing risk of community-acquired TB with age of the household contact, consistent with existing literature. This approach is a useful way to integrate the role of the community in understanding TB disease transmission dynamics in household contact studies.
Assuntos
Teorema de Bayes , Busca de Comunicante/métodos , Características da Família , Modelos Estatísticos , Mycobacterium tuberculosis/isolamento & purificação , Tuberculose Pulmonar/epidemiologia , Adolescente , Brasil/epidemiologia , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Fatores de Risco , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/microbiologia , Uganda/epidemiologiaRESUMO
BACKGROUND: In household contact investigations of tuberculosis (TB), a second tuberculin skin test (TST) obtained several weeks after a first negative result consistently identifies individuals that undergo TST conversion. It remains unclear whether this delay in M. tuberculosis infection is related to differences in the infectious exposure, TST boosting, partial host resistance, or some other factor. METHODS: We conducted a household contact study Vitória, Brazil. Between 2008 and 2013, we identified culture-positive pulmonary TB patients and evaluated their household contacts with both a TST and interferon gamma release assay (IGRA), and identified TST converters at 8-12 weeks post study enrollment. Contacts were classified as TST-positive (≥10 mm) at baseline, TST converters, or persistently TST-negative. We compared TST converters to TST-positive and to TST-negative contacts separately, using generalized estimating equations. RESULTS: We enrolled 160 index patients and 838 contacts; 523 (62.4%) were TST+, 62 (7.4%) TST converters, and 253 (30.2%) TST-. TST converters were frequently IGRA- at 8-12 weeks. In adjusted analyses, characteristics distinguishing TST converters from TST+ contacts (no contact with another TB patient and residence ownership) were different than those differentiating them from TST- contacts (stronger cough in index patient and contact BCG scar). CONCLUSIONS: The individual risk and timing of M. tuberculosis infection within households is variable and dependent on index patient, contact and environmental factors within the household, and the surrounding community. Our findings suggest a threshold effect in the risk of infection in humans.
Assuntos
Tuberculose/diagnóstico , Tuberculose/epidemiologia , Adolescente , Adulto , Brasil/epidemiologia , Criança , Tosse/microbiologia , Características da Família , Feminino , Humanos , Testes de Liberação de Interferon-gama , Masculino , Mycobacterium tuberculosis/patogenicidade , Teste Tuberculínico , Tuberculose/transmissão , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/epidemiologia , Adulto JovemRESUMO
Household contact studies, a mainstay of tuberculosis transmission research, often assume that tuberculosis-infected household contacts of an index case were infected within the household. However, strain genotyping has provided evidence against this assumption. Understanding the household versus community infection dynamic is essential for designing interventions. The misattribution of infection sources can also bias household transmission predictor estimates. We present a household-community transmission model that estimates the probability of community infection, that is, the probability that a household contact of an index case was actually infected from a source outside the home and simultaneously estimates transmission predictors. We show through simulation that our method accurately predicts the probability of community infection in several scenarios and that not accounting for community-acquired infection in household contact studies can bias risk factor estimates. Applying the model to data from Vitória, Brazil, produced household risk factor estimates similar to two other standard methods for age and sex. However, our model gave different estimates for sleeping proximity to index case and disease severity score. These results show that estimating both the probability of community infection and household transmission predictors is feasible and that standard tuberculosis transmission models likely underestimate the risk for two important transmission predictors. Copyright © 2017 John Wiley & Sons, Ltd.