Familial outbreak of disseminated multidrug-resistant tuberculosis and meningitis

Rapidly progressive multidrug-resistant tuberculosis (MDR-TB) is well docum ented in human immunodeficiency virus (HIV) positive subjects, but it is no t fully recognised in HN-negative subjects in the familial environment. We report three cases of MDR-TB in three young HIV-negative subjects from the same family. All the patients showed signs of meningitis during the course of their disease, and in two cases a resistant strain of Mycobacterium tube rculosis was isolated in cerebrospinal fluid. Two of the three subjects die d from neurological complications; the other was successful treated utilisi ng both systemic and intrathecal therapy for tuberculous meningitis. By a r etrospective analysis of DNA obtained from Lowenstein-Jensen cultures, the strains were confirmed as M. tuberculosis resistant to rifampicin and isoni azid, and were closely related in the two cases where specimens were availa ble for analysis. The resistance was acquired in two patients initially inf ected with a susceptible strain; in the other patient, the resistance was p resent on the first sensitivity test for which results were available. This report demonstrates the high risk of fatality from MDR-TB for HIV-negative subjects in the absence of reliable early diagnostic and preventive tools. It also reinforces the concept that genetic susceptibility to M. tuberculo sis may be an important factor in the clinical presentation and outcome of MDR-TB.