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The Effect of Dysglycemia on Mycobacterium tuberculosis Transmission to Close Contacts of Persons with Pulmonary Tuberculosis

Betânia Nogueira 2,3,4* , María B. Arriaga 1,2,3* , Michael S. Rocha 2,4* ,Vanessa Nascimento 2,4,5* , Mariana Araújo-Pereira 1,2,3 , Alexandra B. Souza 6 , Alice M. S. Andrade 1,2 , Alysson G. Costa 6 , Adriano Gomes-Silva 7 , Elisangela C. Silva 8 , Marina C. Figueiredo 9 , Megan M. Turner 9 , Betina Durovni 10 , José R. Lapa-e-Silva 8 , Afrânio L. Kritski 8 , Solange Cavalcante 7,10 , Valeria C. Rolla 7 , Marcelo Cordeiro-Santos 6 , Timothy R. Sterling 9** , Bruno B. Andrade 1,2,3,4,5,11** for the RePORT Brazil consortium

1 Laboratório de Inflamação e Biomarcadores, Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Brazil; 2 Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador, Brazil

3 Faculdade de Medicina, Universidade Federal da Bahia, Salvador, Brazil; 4 Instituto Brasileiro para Investigação da Tuberculose, Fundação José Silveira, Salvador, Brazil

5 Escola Bahiana de Medicina e Saúde Pública, Salvador, Brazil

6 Fundação Medicina Tropical Dr Heitor Vieira Dourado, Manaus, Brazil; 7 Instituto Nacional de Infectologia Evandro Chagas, Rio de Janeiro, Brazil; 8 Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; 9 Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA; 10 Secretaria Municipal de Saúde do Rio de Janeiro (Clínica da Família Rinaldo Delamare)-Rocinha, Rio de Janeiro, Brazil

11 Curso de Medicina, Universidade Salvador (UNIFACS), Laureate University, Salvador, Brazil

Background: It is unknown whether diabetes (DM) is associated with risk of Mycobacterium tuberculosis (Mtb) transmission.

Methods: We assessed the epidemiological and clinical characteristics of patients with culture- confirmed pulmonary TB and their close contacts, enrolled in a multicenter prospective cohort in Brazil from June 2015-June 2019. Participants were investigated at baseline (month 0) and 6 months after enrollment. QuantiFERON (QTF) positivity at baseline and conversion (from negative at month 0 to positive at month 6) were compared between subgroups of contacts according to glycemic status of the TB index case. Dysglycemia was defined using HbA1c results (prediabetes= HbA1c 5.7-6.4%; diabetes= HbA1c≥ 6.5%). Multivariable mixed-effects logistic regression models were performed to test independent associations with baseline QTF positivity and conversion.

Findings: There were 592 TB cases (152 with DM, 227 with prediabetes, 213 normoglycemic) and 1784 TB contacts (658 QTF-positive at baseline, 106 QTF converters, 809 QTF-negative, 47 QTF-indeterminate, 175 lost to follow-up). The multivariable mixed-effects logistic regression models showed that having aTB source case with prediabetes, AFB-positive, and pulmonary cavities, as well as living with someone who smoked, were independently associated with positive QTF in contacts at baseline; HIV in the source case was associated with decreased risk of positive QTF at baseline. DM, persistent cough, AFB-positive and cavitary pulmonary lesions in TB source cases were associated with QTF conversion in contacts.

Conclusion: Contacts of pulmonary TB patients with DM were at increased risk of QTF conversion. Close follow-up of the contacts of TBDM patients could be a strategy for TB control.