Classification and Pathogenesis of Meningococcal Infections

Abstract

The clinical symptoms induced by Neisseria meningitidis reflect compartmentalized intravascular and intracranial bacterial growth and inflammation. In this chapter, we describe a classification system for meningococcal disease based on the nature of the clinical symptoms. Meningococci invade the subarachnoid space and cause meningitis in as many as 50-70% of patients. The bacteremic phase is moderate in patients with meningitis and mild systemic meningococcemia but graded high in patients with septic shock. Three landmark studies using this classification system and comprising 862 patients showed that 37-49% developed meningitis without shock, 10-18% shock without meningitis, 7-12% shock and meningitis, and 18-33% had mild meningococcemia without shock or meningitis. N. meningitidis lipopolysaccharide (LPS) is the principal trigger of the innate immune system via activation of the Toll-like receptor 4-MD2 cell surface receptor complex on myeloid and nonmyeloid human cells. The intracellular signals are conveyed via MyD88-dependent and -independent pathways altering the expression of >4,600 genes in target cells such as monocytes. However, non-LPS molecules contribute to inflammation, but 10-100-fold higher concentrations are required to reach the same responses as induced by LPS. Activation of the complement and coagulation systems is related to the bacterial load in the circulation and contributes to the development of shock, organ dysfunction, thrombus formation, bleeding, and long-term complications in patients. Despite rapid intervention and advances in patient intensive care, why as many as 30% of patients with systemic meningococcal disease develop massive meningococcemia leading to shock and death is still not understood.

Lipooligosaccharide Structures of Invasive and Carrier Isolates of Neisseria meningitidis Are Correlated with Pathogenicity and Carriage

“…In addition, our model is in accordance with several aspects of the clinical progression of N. meningitidis infections. Despite the fulminant nature of meningococcal infections that can lead to death within a few hours after the first onset of symptoms, the time from exposure to N. meningitidis to disease is thought to be 7-10 days, which would enable variable production of meningococcus-specific antibody to play a role in the disease (65,66). Clinical observations have divided meningococcal infections into two groups based on the time elapsed between the first observation of symptoms and hospital admission.…”

Humanized Mouse Model to Study Bacterial Infections Targeting the Microvasculature

“…Skin biopsies from clinical patients show bacteria associated with microvessels, often filling the vessels 2 . Apart from the bacteria, extensive thrombosis, coagulation, congestion and vascular leak is seen in the purpuric regions [3][4][5] . This vascular damage can lead to extensive necrosis of the skin and surrounding tissues, resulting in debridement and even amputation in meningococcal survivors.…”

Functional Annotation and Classification of the Hypothetical Proteins of <i>Neisseria meningitides</i> H44/76

“…Among children and infants, it can get its way to the brain by invading the respiratory epithelial tissues and then crossing the blood brain barrier. The common symptoms are high fever, lethargy, confusion, nausea, neck stiffness, vomiting, and petechial rash [3] [4]. Surveillance is of utmost importance for getting better grasp of meningococcal diseases as they may lead to epidemics and outbreaks [5] [6].…”