Feasibility of identifying household contacts of rifampin- and multidrug-resistant tuberculosis cases at high risk of progression to tuberculosis disease

Post Date: 
Clinical Infectious Diseases

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

We conducted a cross-sectional study of adult MDR-TB cases and their HHCs in eight high-TB-burden countries. HHCs underwent symptom screening, chest radiography (CXR), sputum TB bacteriology, TB infection (TBI) testing (tuberculin skin test and interferon gamma release assay) and HIV testing.

From October 2015 to April 2016, 1016 HHCs from 284 MDR-TB cases were enrolled. At diagnosis, 69% of MDR-TB cases were acid fast bacilli sputum smear-positive and 43% had cavitary disease; at study entry 35% remained smear-positive after a median MDR-TB treatment duration of 8.8 weeks. Nine HHCs were diagnosed with TB prior to entry and excluded. Of the remaining 1007 HHCs, 41% were male and the median age was 25 years. 121 (12%) HHC had new TB identified: 17 (2%) were confirmed; 33 (3%) probable; and 71 (7%) possible TB. 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%) <5 years; 63 (6%) 5 and HIV-infected; and 610 (61%) 5 years, HIV-negative/unknown, and TBI positive. Only 21 (2%) HHCs were on preventive therapy.

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.

Gupta A, Swindells S, Kim S, Hughes MD, Naini L, Wu X, Dawson R, Mave V, Sanchez J, Mendoza A, Gonzales P, Kumarasamy N, Comins K, Conradie F, Shenje J, Fontain SN, Garcia-Prats A, Asmelash A, Nedsuwan S, Mohapi L, Lalloo UG, Ferreira ACG, Mugah C, Harrington M, Jones L, Cox S, Smith B, Shah NS, Hesseling AC, Churchyard G, ACTG 5300/IMPAACT I2003 PHOENIx Feasibility study team. Feasibility of identifying household contacts of rifampin- and multidrug-resistant tuberculosis cases at high risk of progression to tuberculosis disease. Clin Infect Dis. 2019 Mar 28. pii: ciz235. doi: 10.1093/cid/ciz235. [Epub ahead of print] PMID: 30942853; PMCID: PMC7188224.
  • Byramjee Jeejeebhoy Government Medical College-Johns Hopkins University Clinical Research Site, Pune, India
  • University of Nebraska Medical Center, Omaha, NE 
  • Frontier Science & Technology Research Foundation, Amherst, NY
  • Harvard T.H. Chan School of Public Health, Boston, MA 
  • Social & Scientific Systems, Silver Spring, MD 
  • University of Cape Town Lung Institute and Department of Medicine, University of Cape Town, South Africa
  • Asociación Civil Impacta Salud y Educación, San Miguel CRS, Lima, Peru
  • Asociación Civil Impacta Salud y Educación, Barranco CRS, Lima, Peru
  • Chennai Antiviral Research and Treatment Clinical Research Site, Chennai, India
  • TASK Applied Science Clinical Research Site, Bellville, South Africa
  • University of the Witwatersrand Helen Joseph Hospital, Johannesburg, South Africa
  • South African Tuberculosis Vaccine Initiative, Cape Town, South Africa
  • GHESKIO Centers Institute of Infectious Diseases and Reproductive Health, Port-au-Prince, Haiti
  • Desmond Tutu TB Centre, Depatment of Paediatrics and Child Health, Stellenbosch University, Cape Town, South Africa
  • Gaborone Clinical Research Site, Gaborone, Botswana
  • PHPT-Changrai Prachanukroh Hospital, Chiang Rai, Thailand
  • Soweto Clinical Research Site, University of the Witwatersrand, Johannesburg, South Africa
  • Durban International Clinical Research Site, Durban University of Technology, South Africa
  • Instituto Nacional de Infectologia - INI/Fiocruz, Brazil
  • Kenya Medical Research Institute, Kisumu, Kenya
  • Treatment Action Group, New York, NY
  • National Institutes of Health, Bethesda, MD
  • U.S. Centers for Disease Control and Prevention, Atlanta, GA
  • University of Witwatersrand, School of Public Health, Johannesburg, South Africa
  • Advancing Care and Treatment, South African Medical Research Council, Johannesburg, South Africa