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Familial outbreak of disseminated multidrug-resistant tuberculosis and meningitis
M Sofia1, M Maniscalco, N Honoré
1Department of Respiratory Disease, University of Naples Federico II, Italy.
Abstract:
Rapidly progressive multidrug-resistant tuberculosis (MDR-TB) is well documented in human immunodeficiency virus (HIV) positive subjects, but it is not fully recognised in HIV-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 tuberculosis was isolated in cerebrospinal fluid. Two of the three subjects died from neurological complications; the other was successful treated utilising both systemic and intrathecal therapy for tuberculous meningitis. By a retrospective analysis of DNA obtained from Lowenstein-Jensen cultures, the strains were confirmed as M. tuberculosis resistant to rifampicin and isoniazid, and were closely related in the two cases where specimens were available for analysis. The resistance was acquired in two patients initially infected with a susceptible strain; in the other patient, the resistance was present 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. tuberculosis may be an important factor in the clinical presentation and outcome of MDR-TB.
Insights
Multidrug-resistant tuberculosis (MDR-TB) can be fatal in HIV-negative individuals, particularly within families. Early diagnosis and preventive strategies are crucial for managing this severe form of TB.
Area of Science:
- Infectious Diseases
- Genetics
- Neurology
Background:
- Multidrug-resistant tuberculosis (MDR-TB) is a significant global health threat, often associated with human immunodeficiency virus (HIV) infection.
- However, its presentation and outcomes in HIV-negative individuals, especially within familial clusters, are less understood.
Observation:
- This study details three cases of rapidly progressive MDR-TB in young, HIV-negative siblings, all presenting with tuberculous meningitis.
- Mycobacterium tuberculosis strains isolated from cerebrospinal fluid showed resistance to key anti-TB drugs, with genetic relatedness observed between strains.
Findings:
- Two of the three affected individuals succumbed to neurological complications, highlighting the aggressive nature of MDR-TB in this population.
- The third patient was successfully treated with a combination of systemic and intrathecal therapies for tuberculous meningitis.
- Genetic analysis revealed that drug resistance was acquired in two cases, while present from the initial diagnosis in the third.
Implications:
- This case series underscores the critical need for enhanced diagnostic and preventive tools for MDR-TB in HIV-negative individuals and families.
- It suggests that genetic susceptibility may play a role in the clinical course and prognosis of MDR-TB.
- The findings emphasize the potential for severe neurological sequelae and high mortality rates in untreated or inadequately treated MDR-TB meningitis.