Feasibility of Identifying Household Contacts of Rifampin-and Multidrug-resistant Tuberculosis Cases at High Risk of Progression to Tuberculosis Disease

Amita Gupta; Susan Swindells; Soyeon Kim; Michael D Hughes; Linda Naini; Xingye Wu; Rodney Dawson; Vidya Mave; Jorge Sanchez; Alberto Mendoza; Pedro Gonzales; Nagalingeswaran Kumarasamy; Kyla Comins; Francesca Conradie; Justin Shenje; Sandy Nerette Fontain; Anthony Garcia-Prats; Aida Asmelash; Supalert Nedsuwan; Lerato Mohapi; Umesh G Lalloo; Ana Cristina Garcia Ferreira; Christopher Mugah; Mark Harrington; Lynne Jones; Samyra R Cox; Betsy Smith; N Sarita Shah; Anneke C Hesseling; Gavin Churchyard

doi:10.1093/cid/ciz235

Feasibility of Identifying Household Contacts of Rifampin-and Multidrug-resistant Tuberculosis Cases at High Risk of Progression to Tuberculosis Disease

Clin Infect Dis. 2020 Jan 16;70(3):425-435. doi: 10.1093/cid/ciz235.

Authors

Amita Gupta^{1

2}, Susan Swindells³, Soyeon Kim⁴, Michael D Hughes⁵, Linda Naini⁶, Xingye Wu⁵, Rodney Dawson⁷, Vidya Mave^{1

2}, Jorge Sanchez⁸, Alberto Mendoza⁹, Pedro Gonzales⁸, Nagalingeswaran Kumarasamy¹⁰, Kyla Comins¹¹, Francesca Conradie¹², Justin Shenje¹³, Sandy Nerette Fontain¹⁴, Anthony Garcia-Prats¹⁵, Aida Asmelash¹⁶, Supalert Nedsuwan¹⁷, Lerato Mohapi¹⁸, Umesh G Lalloo¹⁹, Ana Cristina Garcia Ferreira²⁰, Christopher Mugah²¹, Mark Harrington²², Lynne Jones⁴, Samyra R Cox¹, Betsy Smith²³, N Sarita Shah²⁴, Anneke C Hesseling¹⁵, Gavin Churchyard^{25

26

27}

Affiliations

¹ Johns Hopkins University, Department of Medicine, Baltimore, Maryland.
² Byramjee Jeejeebhoy Government Medical College, Johns Hopkins University Clinical Research Site, Pune, India.
³ University of Nebraska Medical Center, Omaha.
⁴ Frontier Science & Technology Research Foundation, Amherst, New York.
⁵ Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
⁶ Social & Scientific Systems, Silver Spring, Maryland.
⁷ University of Cape Town Lung Institute and Department of Medicine, University of Cape Town, South Africa.
⁸ Asociación Civil Impacta Salud y Educación, Lima, Peru.
⁹ TASK Applied Science Clinical Research Site, Bellville, South Africa.
¹⁰ Chennai Antiviral Research and Treatment Clinical Research Site, India.
¹¹ TASK Applied Science Clinical Research Site, Bellville.
¹² University of the Witwatersrand Helen Joseph Hospital, Johannesburg, South Africa.
¹³ South African Tuberculosis Vaccine Initiative, Cape Town, South Africa.
¹⁴ GHESKIO Centers Institute of Infectious Diseases and Reproductive Health, Port-au-Prince, Haiti.
¹⁵ Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Stellenbosch University, Cape Town, South Africa.
¹⁶ Gaborone Clinical Research Site, Botswana.
¹⁷ PHPT-Changrai Prachanukroh Hospital, Chiang Rai, Thailand.
¹⁸ Soweto Clinical Research Site, University of the Witwatersrand, Johannesburg, South Africa.
¹⁹ Durban International Clinical Research Site, Durban University of Technology, South Africa.
²⁰ Instituto Nacional de Infectologia - INI/Fiocruz, Brazil.
²¹ Kenya Medical Research Institute, Kisumu.
²² Treatment Action Group, New York, New York.
²³ National Institutes of Health, Bethesda, Maryland.
²⁴ US Centers for Disease Control and Prevention, Atlanta, Georgia.
²⁵ Aurum Institute, Parktown, South Africa.
²⁶ University of Witwatersrand, School of Public Health.
²⁷ Advancing Care and Treatment, South African Medical Research Council, Johannesburg, South Africa.

Abstract

Background: We assessed multidrug-resistant tuberculosis (MDR-TB) cases and their household contacts (HHCs) to inform the development of an interventional clinical trial.

Methods: We conducted a cross-sectional study of adult MDR-TB cases and their HHCs in 8 countries with high TB burdens. HHCs underwent symptom screenings, chest radiographies, sputum TB bacteriologies, TB infection (TBI) testing (tuberculin skin test [TST] and interferon gamma release assay [IGRA]), and human immunodeficiency virus (HIV) testing.

Results: From October 2015 to April 2016, 1016 HHCs from 284 MDR-TB cases were enrolled. At diagnosis, 69% of MDR-TB cases were positive for acid-fast bacilli sputum smears and 43% had cavitary disease; at study entry, 35% remained smear positive after a median MDR-TB treatment duration of 8.8 weeks. There were 9 HHCs that were diagnosed with TB prior to entry and excluded. Of the remaining 1007 HHCs, 41% were male and the median age was 25 years. There were 121 (12%) HHCs that had new cases of TB identified: 17 (2%) were confirmed, 33 (3%) probable, and 71 (7%) possible TB cases. The TBI prevalence (defined as either TST or IGRA positivity) was 72% and varied by age, test used, and country. Of 1007 HHCs, 775 (77%) were considered high-risk per these mutually exclusive groups: 102 (10%) were aged <5 years; 63 (6%) were aged ≥5 and were infected with HIV; and 610 (61%) were aged ≥5 years, were negative for HIV or had an unknown HIV status, and were TBI positive. Only 21 (2%) HHCs were on preventive therapy.

Conclusions: The majority of HHCs in these high-burden countries were at high risk of TB disease and infection, yet few were receiving routine preventive therapy. Trials of novel, preventive therapies are urgently needed to inform treatment policy and practice.

Keywords: TB disease; TB infection; household contacts; multidrug-resistant tuberculosis; preventive therapy.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Adult
Child, Preschool
Cross-Sectional Studies
Family Characteristics
Feasibility Studies
Female
Humans
Male
Rifampin / therapeutic use
Tuberculin Test
Tuberculosis*
Tuberculosis, Multidrug-Resistant* / epidemiology

Substances

Rifampin

Abstract

Publication types

MeSH terms

Substances

Grants and funding