The Xpert MTB/RIF Cycle Threshold Value Predicts Mycobacterium tuberculosis Transmission to Close Contacts in a Brazilian Prospective Multicenter Cohort

Author:

Garcia Leandro S12,Costa Allyson G1234,Araújo-Pereira Mariana567,Spener-Gomes Renata12,França Aguiar Amanda1,Souza Alexandra B12,Lima Lucas O A18,Benjamin Aline9,Rocha Michael S710,Moreira Adriana S R11,Silva Jaquelane1,Santos Saulo R N10,Lourenço Maria Cristina9,Figueiredo Marina C12,Turner Megan M12,Kritski Afranio L11,Rolla Valeria C9,Sterling Timothy R12,Andrade Bruno B567ORCID,Cordeiro-Santos Marcelo12, ,Gomes-Silva Adriano,Andrade Alice M S,Bezerra André Luiz,Carvalho Anna Cristina Calçada,Silveira Anna Karla,Nogueira Betânia M F,Carvalho Brenda K S,de Loiola Bruna Pires,Stanis Carolina Arana Schmaltz,de Freitas Medeiros Eline Naiane,Ignácio Francine Peixoto,Santos Hayna Malta,Oliveira Jamile G,Silva Jéssica Rebouças,Neto João Marine,Arriaga María B,Silva-Freitas Maria Luciana,de Melo Mayla Gabriele Miranda,Placido-Pereira Rosa Maria,Almeida-Da-Silveira Samyra,de Souza Nascimento Vanessa

Affiliation:

1. Fundação de Medicina Tropical Doutor Heitor Vieira Dourado, Instituto de Pesquisa Clínica Carlos Borborema , Manaus , Brazil

2. Programa de Pós-Graduação em Medicina Tropical, Universidade do Estado do Amazonas , Manaus , Brazil

3. Escola de Enfermagem de Manaus, Universidade Federal do Amazonas , Manaus , Brazil

4. Diretoria de Ensino e Pesquisa, Fundação Hospitalar de Hematologia e Hemoterapia do Amazonas , Manaus , Brazil

5. Laboratório de Inflamação e Biomarcadores, Instituto Gonçalo Moniz, Fundação Oswaldo Cruz , Salvador , Brazil

6. Faculdade de Medicina, Universidade Federal da Bahia , Salvador , Brazil

7. Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative , Salvador , Brazil

8. Faculdade de Medicina, Universidade Federal do Amazonas , Manaus , Brazil

9. Fundação Oswaldo Cruz, Instituto Nacional de Infectologia Evandro Chagas , Rio de Janeiro , Brazil

10. Fundação José Silveira, Instituto Brasileiro para Investigação da Tuberculose , Salvador , Brazil

11. Programa Acadêmico de Tuberculose, Faculdade de Medicina, Universidade Federal do Rio de Janeiro , Rio de Janeiro , Brazil

12. Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine , Nashville, Tennessee , USA

Abstract

Abstract Background The Xpert MTB/RIF rapid molecular test provides a quantitative measure of Mycobacterium tuberculosis (Mtb) DNA in the form of cycle threshold (Ct) values. This information can be translated into mycobacterial load and used as a potential risk measure of bacterial spread for tuberculosis (TB) cases, which can impact infection control. However, the role of Ct values in assessing Mtb transmission to close contacts has not yet been demonstrated. Methods A prospective study was performed to investigate the association between Xpert MTB/RIF Ct values and Mtb transmission to close contacts of patients with culture-confirmed pulmonary TB in a multicenter Brazilian cohort. We evaluated clinical and laboratory data (age, sex, race, smoking habits, drug use, alcohol use, chest X-ray, Xpert MTB/RIF results) among pulmonary TB cases, and QuantiFERON-TB Gold Plus (QFT-Plus) results at baseline and after 6 months, for close contacts who had a negative result at baseline. Results A total of 1055 close contacts of 382 pulmonary TB cases were included in the study. The median Ct values from TB cases of QFT-Plus–positive (at baseline or 6 months) close contacts were lower compared with those who were QFT-Plus–negative. An adjusted logistic regression demonstrated that reduced Ct values from the index cases were independently associated with QFT-Plus conversion from negative to positive (odds ratio, 1.61; 95% confidence interval, 1.12–2.32) after adjusting for clinical characteristics. Conclusions Close contacts of pulmonary TB index cases who exhibit low Xpert MTB/RIF Ct values displayed higher rates of TB infection, reflecting Mtb transmission.

Funder

Intramural Research Program of the Fundação Oswaldo Cruz

Intramural Research Program of the Fundação José Silveira

Departamento de Ciência e Tecnologia

Secretaria de Ciência e Tecnologia

Ministério da Saúde

National Institutes of Allergy and Infectious Diseases

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

Fundação de Amparo à Pesquisa do Estado do Amazonas

Conselho Nacional de Desenvolvimento Científico e Tecnológico

Publisher

Oxford University Press (OUP)

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