A recently published paper has highlighted the potential of clofazimine to protect the brain and central nervous system against extra-pulmonary TB, according to one of the researchers, Dr Sooraj Baijnath, senior lecturer in pharmaceutical sciences at the University of Kwa-Zulu Natal, Westville Campus. Highlights of the research include evidence that an aerosol challenge leads to the dissemination of Mycobacterium tuberculosis (M.tb) into the brain, in a murine model; linezolid monotherapy does not protect the central nervous system (CNS) against the development of extra-pulmonary TB; and clofazimine monotherapy protects against M.tb of the CNS, in a murine model.
Abstract
Background: Tuberculosis (TB) has been the scourge of the human race for many decades, claiming countless number of lives along the way. This is further complicated by the ability of Mycobacterium tuberculosis (M.tb) to infect extra-pulmonary sites, more specifically the brain. These forms of TB are difficult to treat due to the problems associated with drug delivery across the blood brain barrier (BBB). Linezolid (LZD and clofazimine (CFZ) are two of the more promising anti-TB antibiotics in recent times.
Methods: In this study Balb/c mice were aerosol infected with M.tb H37Rv and treated for four weeks with both LZD (100mg/kg.b.w) and CFZ (100mg/kg.b.w). Concurrently, we investigated if an aerosol TB infection would lead to the dissemination of TB bacilli into the brain. Post-treatment brain and lung CFU's were determined together with serum, lung and brain drug concentrations.
Results: CFZ displayed a strong bactericidal effect in the lung, while LZD had a bacteriostatic effect. M.tb appeared after one week post-infection in the untreated group (2.38±0.43 log10CFU) and more surprisingly after two weeks' post-infection in the LZD (1.14±0.99 log10CFU). TB bacilli could not be detected in the brains of the CFZ group.
Conclusions: To the best of our knowledge, this is the first study to show the appearance of M.tb in the brain after an aerosol TB infection in a mouse. This study may advocate for the use of CFZ as a prophylactic treatment to prevent the development of extra-pulmonary TB of the CNS, using a two-pronged approach.
Authors
Sooraj Baijnath, Chivonne Moodley, Bongani Ngcobo, Sanil D Singh, Hendrik G Kruger, Per I Arvidsson, Tricia Naicker, Alexander Pym, Thavendran Govender
[link url="http://www.ijaaonline.com/article/S0924-8579(17)30312-6/fulltext"]International Journal of Microbial Agents abstract[/link]