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Galea, J.

Publications and source records attributed to Galea, J..

2 recordsLinked to original sources
bioRxiv2018

Isoniazid preventive therapy protects against tuberculosis among household contacts of isoniazid-resistant patients.

BackgroundThe World Health Organization recommends the use of isoniazid (INH) alone or combination INH and rifapentine therapy to treat latent tuberculosis infection (LTBI) in groups at high risk of tuberculosis (TB) progression. The recent rise of INH- and multi-drug resistant (MDR) TB has complicated the choice of LTBI treatment regimen. We examine the risk of TB disease among household contacts (HHCs) who received INH after being exposed to patients with drug-sensitive, INH-resistant, or MDR tuberculosis. MethodsIn this prospective cohort study conducted Between September 2009 and August 2012 in Lima, Peru, we identified 4,500 index TB patients and measured incident TB disease in their 14,044 HHCs over a one-year follow-up period. HHCs under 19 years of age were offered INH preventive therapy (IPT). We used a Cox frailty proportional hazards model to evaluate whether the effect of IPT on incident TB disease varied by the resistance profile of the index case. We repeated the analyses in a second independent dataset. FindingsAmong 4,216 HHCs under 19 years of age, 2,106 (50%) initiated IPT at enrolment. The protective effect of INH was more extreme in HHCs exposed to drug-sensitive (Hazard Ratio [95% confidence interval]=0{middle dot}2[0{middle dot}20-0{middle dot}50]) and to MDR-TB (0{middle dot}26[0{middle dot}08-0{middle dot}77]) compared to those exposed to mono-INH-resistant (0{middle dot}80[0{middle dot}23 to 2{middle dot}79]). Among those who received at least three months of INH, effectiveness increased across all three groups (INH-sensitive:0{middle dot}20 [0{middle dot}10 to 040]; MDR:0{middle dot}16 [0 02-127]; mono-INH-resistant:0{middle dot}72 [0{middle dot}16-3{middle dot}16]). In the second independent study, TB occurred in none of the 76 HHCs who received IPT compared to 3% (8/273) of those who did not. InterpretationWe found that IPT use is associated with reduced incidence of TB disease among contacts of MDR-TB patients. This finding suggests that INH may have role in the management of MDR-LTBI. FundingNational Institutes of Health and the National Institute of Allergy and Infectious Diseases CETR (U19AI109755) and TBRU (U19AI111224)

epidemiology↗
bioRxiv2018

RESISTANCE AT NO COST: THE TRANSMISSIBILITY AND POTENTIAL FOR DISEASE PROGRESSION OF DRUG-RESISTANT M. TUBERCULOSIS

BackgroundThe future trajectory of drug resistant tuberculosis strongly depends on the fitness costs of drug resistance mutations. Here, we measured the association of phenotypic drug resistance and the risk of TB infection and disease among household contacts (HHCs) of patients with pulmonary TB.\n\nMethodsWe evaluated 12767 HHCs of patients with drug sensitive and resistant pulmonary TB at baseline, two, six, and 12 months to ascertain infection status and to determine whether they developed tuberculosis disease. We also assessed the impact of drug resistance phenotype on the likelihood that a TB strain shared a genetic fingerprint with at least one other TB patient in the cohort.\n\nFindingsAmong 3339 TB patients for whom were DST available, 1274 (38%) had TB that was resistant to at least one drug and 478 (14*3%) had multi-drug resistant (MDR) TB, i.e. TB resistant to both INH and rifampicin. Compared to HHCs of drug sensitive TB patients, those exposed to a patient with MDR-TB had an 8% (95% CI: 4-13%) higher risk of infection by the end of follow up. We found no statistically significant difference in the relative hazard of incident TB disease among HHCs exposed to MDR-TB compared to DS-TB (Adjusted HR 1*28 [(95% CI: *9-1*83]). Patients with MDR-TB were more likely to be part of a genetic cluster than were DS-TB patients.\n\nInterpretationClinical strains of MDR M. tuberculosis are neither less transmissible than drug sensitive strains nor less likely to cause disease. (ClinicalTrials.gov number, NCT00676754)\n\nFundingNational Institutes of Health: NIH/NIAID CETR U19AI109755\n\nStatementAll authors have seen the manuscript and approved the manuscript.

epidemiology↗