**2. Epidemiological data on the HIV/TB co-infection**

TB is preventable and curable and its eradication was considered possible before the spread of the HIV pandemic. Since then the pathogenic mechanisms of HIV and TB have been closely entwined. Such is the complementary evolution of HIV and TB that the HIV/TB co-infection has been referred to as a ''syndemic'' by some authors [1]. The term ''syndemic'' reflects the similar social, epidemiological and pathological settings of both diseases. The close interrela‐ tion between HIV and tuberculosis overcomes by far the interactions between other commun‐ ity acquired infections. Thus epidemiological studies suggest that as many as 50% of the HIV patients develop mycobacterial infections. The rate of extrapulmonary TB could account for more than 50% of cases presenting with HIV and TB coinfection. In the pre-AIDS era the immunodeficiency status incriminated in the pathogenesis of extrapulmonary TB was induced by autoimmune diseases, aging, diabetes, alcoholism, malnutrition, malignancies or immu‐ nosuppressive chemotherapy. However the total amount of extrapulmonary TB in non-HIV immunosupressed patients did not exceed 15% of all TB cases. In addition meningitis and other forms of NTB represented less than 1% of all TB cases in non-HIV patients [2,3] but presently account for 10% of all TB cases in HIV patients [4]. Tuberculous meningitis (TBM) occurs in 5%-8% of the HIV patients [5,6] but tuberculomas and abscesses are also a common finding in late stages of AIDS [7]. Regarding the CNS infection with non-tuberculous mycobacteria one of the most important risk factors is the progressive immunodeficiency induced by HIV infection.

masses further developing into tuberculomas or tuberculous abscesses [ 10,11,12]. In addition HIV patients characteristically present several TB cerebral lesions evolving simultaneously.

Neurotuberculosis and HIV Infection http://dx.doi.org/10.5772/54631 295

Below we enlisted the factors involved in the clinical progression and persistent CNS invasion

The site of extrapulmonary mycobacterial infections and especially the CNS invasion depend on the efficacy of cell-mediated immunity. Both the HIV infection and TB trigger

On the other hand humoral immnity is increased but inefficient. The high titres of antimyco‐ bacterial antibodies are not protective and could instead result in numerous complications. The most important mechanism behind the cellular immunosuppression in the HIV-TB co-

*Macrophage and lymphocyte cells.* Macrophages play a crucial role in both HIV and mycobac‐ terial infections. As phagocytes of the innate immunity they are considered the main cells involved in the immune response against mycobacteria.Infected macrophages recruit addi‐ tional immune cells such as dendritic cells and T cell lymphocytes and release numerous chemokines and cytokines to form granulomas. The latter are specific stable inflammatory structures limiting the growth of mycobacteria. At the same time mycobacteria could devel‐ op inside macrophages from granulomas thus ensuring their persistence. In addition macro‐ phages infected with Mycobacterium tuberculosis (M. tbc) augment the expression of the C-C chemokine receptor type 5, also known as CCR5, the most important HIV coreceptor [13]. Therefore infected macrophages perform a significant role in the protection and transport of

With the passing of time some of the macrophages infected with mycobacteria suffer apoptosis leading to a numeric decrease of the most important cells involved in the defence against mycobacteria invasion. Moreover HIV is directly responsible for the depletion of CD4+ T lymphocytes through its cytopathic effect and anti-gp120 antibodies. The depletion of CD4+ T lymphocytes raises the susceptibility to TB and most notably towards neurologic forms of TB [14]. In this respect the decreasing CD4+ T cell count was proven to vary inversely with the incidence of NTB. Most patients with HIV and NTB display a CD4+ T cell count below 200

*The Cytokine dysregulation*. Both HIV and mycobacteria are intracellular pathogens. Their presencestimulates thereleaseofcytokinesbymacrophagesandTh1cellswhichinturnregulate the cells involved in the immune response. The stability of the granuloma is usually ensured by a high number of CD4+ T and CD8+ lymphocytes along with a Th1 cytokine profile represent‐ ed by IFN -γ and TNF-α. [15].TNF-α is a pro-inflammatory cytokine released at high levels by CD4+T cells and macrophages coinfected with mycobacteria and HIV. The role of TNF-α in the clinical outcome of the 2 diseases is contradictory. Regarding its role in the control of tuberculo‐

mechanisms of invasion with mycobacteria and HIV are closely interwined.

unlike patients with pulmonary TB who commonly present with a CD4+T cell count,

. In conclusion in the late stages of infection the main pathogenic

complex mechanisms which increase the cellular immunosuppresion.

infection is the severe depletion of macrophage and lymphocyte cells.

with mycobacteria in HIV patients.

**1.** *The cellular immunosuppression in TB and HIV infection.*

mycobacteria and HIV to other tissues including the brain.

cells/ mm3

between 250 and 550 cells/ mm3

Co-infection with HIV not only increases the risk for central nervous system (CNS) TB [17] but also alters the clinical signs, delays the diagnosis and worsens the prognosis [8]. Thus the mortality of HIV patients with TBM is as high as 63% and nearly half of deaths occur in the first 21 days [9].
