Clinical recommendations for diagnosis and management of Mendelian susceptibility to mycobacterial disease in resource-limited settings.

BACKGROUND

Mendelian susceptibility to mycobacterial disease (MSMD) is a rare inborn error of immunity caused by defects in IL-12 or IFN-γ signaling pathways, essential for intracellular pathogen control. While classically linked to nontuberculous mycobacteria, MSMD also predisposes to bacterial, fungal, and viral infections.

OBJECTIVE

We sought to provide a practical framework for diagnosing and managing MSMD in African settings. Recommendations integrate clinical evaluation, baseline immunologic testing, and molecular diagnostics.

METHODS

A review of clinical presentation, diagnostic strategies, and therapeutic approaches was conducted, emphasizing applicability in resource-limited environments.

RESULTS

MSMD presents across a wide clinical spectrum that includes severe disseminated early-onset infections and localized later-onset disease. While classically characterized by increased susceptibility to nontuberculous mycobacteria, MSMD also predisposes to bacterial, fungal, and viral infections. Standard immunologic screening often yields unremarkable findings, necessitating a tiered diagnostic approach that includes molecular testing for confirmation. Long-term antimicrobial therapy remains the cornerstone of management, with prophylaxis warranted in recurrent or severe cases. Early identification significantly reduces morbidity and mortality. Molecular diagnostic methods facilitate genotype-guided management, enabling precision medicine approaches in this context.

CONCLUSION

Timely recognition of MSMD, particularly in tuberculosis-endemic settings, is critical to prevent severe disease progression. A structured diagnostic algorithm, combined with molecular testing and individualized treatment strategies, enhances outcomes. MSMD underscores the significance of genotype-driven management.