Systemic meningococcal disease (SMD) is purulent meningitis caused by the Neisseria meningitidis (Nm). In the case of purulent cerebrospinal meningopathy, the pathogenic bacteria invade the blood circulation from the nasopharynx and eventually invade the meninges and spinal cord membranes. The main clinical manifestations are meningeal irritation such as fever, vomiting, headache, and purulent changes in cerebrospinal fluid. In addition, Nm may not invade the meninges but only manifest as sepsis, and severe cases may show fulminant attacks, especially in children. Endotoxin is a cell wall component of many Gram-negative bacteria, which can release certain pyrogens, so it plays a role as one of the main pathogenic factors of Nm. It has been reported that the endotoxin concentration in plasma and cerebrospinal fluid of patients is higher than normal, so endotoxin detection is of great significance for guiding clinical treatment and estimating prognosis.
Figure 1. Anatomical considerations for the diagnosis of bacterial meningitis. (Van D B D, et al., 2016)
There are a variety of clinical syndromes caused by SMD, ranging from fulminant meningococcal sepsis with septic shock, death, and multiorgan failure to benign meningococcal bacteremia that is self-limited. Existing in vitro and animal model studies have confirmed that SMD is caused by bacterial endotoxins, which are potent triggers of various pathophysiological processes. Endotoxin is a kind of lipopolysaccharide (LPS), which is derived from the outer membrane of Gram-negative bacteria. The outer lipid component of the outer membrane of the cell wall is composed of endotoxin molecules, which are released after cell death or decomposition. It can cause fever, hemodynamic changes, disseminated intravascular coagulation, and shock. It has been reported in the literature that the limulus test is sensitive for the diagnosis of meningitis infected by Gram-negative bacteria, and generally, the false negative results are extremely low. Preliminary screening showed that high endotoxin levels in cerebrospinal fluid were closely related to shock and death in children with meningitis. The means of clinical diagnosis of SMD are usually the detection of blood, cerebrospinal fluid examination, bacteriological examination, and immune serological examination. Although the accuracy is high, disadvantages include being time-consuming, sensitive, and prone to brain herniation after lumbar puncture. Therefore, the measured quantitative value of endotoxin has a certain correlation with the clinical course, which is of great significance in assisting clinical measures and prognosis.
A recent study of meningitis patients showed abnormally high endotoxin concentrations in plasma and cerebrospinal fluid, accompanied by severe electroencephalogram (EEG) abnormalities. The bacterial endotoxin inspection method is to use a Limulus reagent to detect or quantify the bacterial endotoxin produced by Gram-negative bacteria and judge whether the bacterial endotoxin content in the test product meets the regulations. The reaction mechanism of the Limulus reagent method is that bacterial endotoxin activates a series of coagulation enzyme reactions in the blood cell lysate with the participation of divalent cations. It is a simple, rapid, quantitatively accurate, and highly sensitive method for diagnosing SMD by evaluating the level of endotoxin in a patient's blood, cerebrospinal fluid, or other body fluids. Consequently, an accurate estimation of prognosis and clinical treatment can depend on the detection of endotoxin concentrations in the future.
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