Participants had a structured, stepwise diagnostic algorithm performed of blood cryptococcal antigen (CrAg), CSF CrAg, Xpert MTB/RIF for tuberculous (TB) meningitis (TBM), Biofire multiplex polymerase chain reaction, and traditional microscopy and cultures.
Acid-fast bacilli were demonstrated in 41% of patients (81/195), and cultures for Mycobacterium tuberculosis were positive in 51% (148/292) of tested specimens (predominantly sputum, CSF, and bronchial lavage).
As translated to human disease, these findings suggest vaccine-mediated expansion of GM-CSF-producing T cells could be an effective prophylactic or therapeutic TB strategy.
Of 21 initial cytokines analysed, IFN-γ and six other candidates (interleukin [IL] 2, inducible protein 10 [IP-10], IL-13, IL-1α, tumour necrosis factor alpha [TNF-α] and granulocyte-macrophage colony-stimulating factor [GM-CSF]) were significantly more elevated in children with TB and those with LTBI than in the non-infected controls.
Mice deficient for granulocyte-macrophage colony-stimulating factor (GM-CSF<sup>-/-</sup>) are highly susceptible to infection with <i>Mycobacterium tuberculosis</i>, and clinical data have shown that anti-GM-CSF neutralizing antibodies can lead to increased susceptibility to tuberculosis in otherwise healthy people.
Our data demonstrate that BCG-prime and DNA vaccine expressing Ag85A and GM-CSF boost provides a rational strategy for further development of DNA vaccine against M. tuberculosis infection.
Granulocyte-macrophage colony-stimulating factor (GM-CSF)-induced human monocyte-derived macrophage (GM-Mphi) or macrophage CSF (M-CSF)-induced human monocyte-derived Mphi (M-Mphi) are distinct in terms of the resistance to Mycobacterium tuberculosis.