Preventive therapy for child contacts of multidrug-resistant tuberculosis: a prospective cohort study.
BACKGROUND
Evidence is limited to guide the management of children exposed to multidrug-resistant (MDR) tuberculosis. We aimed to study the tolerability and toxicity of a standard preventive therapy regimen given to children exposed to infectious MDR tuberculosis, and explore risk factors for poor outcome.


METHODS
In this prospective cohort study in the Western Cape, South Africa, children <5 years of age, or human immunodeficiency virus (HIV)-positive children aged <15 years, were recruited from May 2010 through April 2011 if exposed to an ofloxacin-susceptible, MDR tuberculosis source case. Children were started on preventive therapy as per local guidance: ofloxacin, ethambutol, and high-dose isoniazid for 6 months. Standardized measures of adherence and adverse events were recorded; poor outcome was defined as incident tuberculosis or death from any cause.


RESULTS
One hundred eighty-six children were included, with a median age of 34 months (interquartile range, 14-47 months). Of 179 children tested for HIV, 9 (5.0%) were positive. Adherence was good in 141 (75.8%) children. Only 7 (3.7%) children developed grade 3 adverse events. One child (0.5%) died and 6 (3.2%) developed incident tuberculosis during 219 patient-years of observation time. Factors associated with poor outcome were age <1 year (rate ratio [RR], 10.1; 95% confidence interval [CI], 1.65-105.8; P = .009), HIV-positive status (RR, 10.6; 95% CI, 1.01-64.9; P = .049), exposure to multiple source cases (RR, 6.75; 95% CI, 1.11-70.9; P = .036) and poor adherence (RR, 7.50; 95% CI, 1.23-78.7; P = .026).


CONCLUSIONS
This 3-drug preventive therapy regimen was well tolerated and few children developed tuberculosis or died if adherent to therapy. The provision of preventive therapy to vulnerable children following exposure to MDR tuberculosis should be considered.
Desmond Tutu Tuberculosis Centre.
James A
JA
Seddon
Anneke C
AC
Hesseling
Heather
H
Finlayson
Katherine
K
Fielding
Helen
H
Cox
Jennifer
J
Hughes
Peter
P
Godfrey-Faussett
H Simon
HS
Schaaf
D000995:Antitubercular Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002675:Child, Preschool; D004977:Ethambutol / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D015658:HIV Infections / Q000453:epidemiology / Q000382:microbiology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007538:Isoniazid / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D015242:Ofloxacin / Q000009:adverse effects / Q000627:therapeutic use; D011446:Prospective Studies; D012307:Risk Factors; D013019:South Africa / Q000453:epidemiology; D016896:Treatment Outcome; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy* / Q000453:epidemiology / Q000517:prevention & control* / Q000821:virology
D000995:Antitubercular Agents; D004977:Ethambutol; D015242:Ofloxacin; D007538:Isoniazid
child; drug-resistant; pediatric; preventive therapy; tuberculosis