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

Citation: 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

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https://www.ncbi.nlm.nih.gov/pubmed/30942853

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 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.

RESULTS:
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.

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.

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