Pathogenesis and Pathophysiology of Pneumococcal Meningitis

Abstract

SUMMARY Pneumococcal meningitis continues to be associated with high rates of mortality and long-term neurological sequelae. The most common route of infection starts by nasopharyngeal colonization by Streptococcus pneumoniae , which must avoid mucosal entrapment and evade the host immune system after local activation. During invasive disease, pneumococcal epithelial adhesion is followed by bloodstream invasion and activation of the complement and coagulation systems. The release of inflammatory mediators facilitates pneumococcal crossing of the blood-brain barrier into the brain, where the bacteria multiply freely and trigger activation of circulating antigen-presenting cells and resident microglial cells. The resulting massive inflammation leads to further neutrophil recruitment and inflammation, resulting in the well-known features of bacterial meningitis, including cerebrospinal fluid pleocytosis, cochlear damage, cerebral edema, hydrocephalus, and cerebrovascular complications. Experimental animal models continue to further our understanding of the pathophysiology of pneumococcal meningitis and provide the platform for the development of new adjuvant treatments and antimicrobial therapy. This review discusses the most recent views on the pathophysiology of pneumococcal meningitis, as well as potential targets for (adjunctive) therapy.

Functional polymorphisms of macrophage migration inhibitory factor as predictors of morbidity and mortality of pneumococcal meningitis

“…These results suggest that a vigorous MIF response is detrimental in patients with pneumococcal meningitis, a finding consistent with the harmful consequences of robust proinflammatory cytokine responses on brain edema and neuronal damage in the course of bacterial meningitis (26). Up to now, studies of polymorphisms of cytokine genes have failed to demonstrate association between TNF, IL6, IL10, or LTA and the susceptibility to or the outcome of bacterial meningitis (2).…”

“…Carriages of the CATT 7 and −173 C high-expression MIF alleles were associated with unfavorable outcome (P = 0.005 and 0.003) and death (P = 0.03 and 0.01). In a multivariate logistic regression model, shock [odds ratio (OR) 26.0, P = 0.02] and carriage of the CATT 7 allele (OR 5.12, P = 0.04) were the main predictors of mortality. MIF levels in the cerebrospinal fluid were associated with systemic complications and death (P = 0.0002).…”

Polymorphisms in DNA Repair Gene XRCC1 (Arg194Trp) and (Arg399Gln) and their Role in the susceptibility of Bacterial Meningitis

“…The disease evolution is mainly influenced by the host immune response determined by several genes that regulate the intensity of the inflammatory response to infection [8][9][10][11]. In previous work, we obtained data showing association of the SNPs APEX1Asn148Glu, OGG1 Ser326Cys, and PARP-1 Val762Ala with BM.…”

“…Their deficiency may cause predisposition to diseases but in excess or in the wrong tissues can cause serious complications as observed in BM [8][9][10][11]. Some BER enzymes as APEX1, OGG1 and PARP-1 were implicated in the regulation of expression of some cytokines [6].…”

“…In this step, the immune defense system is important to combat the pathogens, avoiding the disease progression [8,9]. Thus, deficiency in the innate or acquired immune response may cause predisposition to disease [10,11].…”