The Clinical Importance of the Treating a Meningococcal Meningitis (Essay Sample)

NEISSERIA MENINGITIDIS
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Introduction
Meningococcal meningitis is a fatal disease that affects many individuals aged between 15 and 24 years. The past decade has witnessed an increase in the reported cases of individuals having meningitis (Strunk & Rocchiccioli 2010). The availability of a vaccine implies that it is possible to protect the individuals against the disease. In the United States, young adults and adolescents account for approximately 30% of all the reported meningitis cases as observed by Struck and Rocchiccioli (Strunk & Rocchiccioli 2010). Neisseria meningitidis remains to be the primary cause of meningitis and severe sepsis across the globe. The bacterium is only found in humans. Consequently, it must coexist continually with the immune system as noted by Lo et al. (2009). The essay examines the clinical importance of the pathogen and the need for further research on its molecular infection mechanisms. In addition, the paper discusses the potential application of the new knowledge in the treatment of the pathogen.
The Molecular Infection Mechanisms of Neisseria Meningitis
According to Lo et al. (2009), the pathogen uses many mechanisms to protect itself against antimicrobial proteins, the complement system, and phagocytes. The pathogen also mimics the host molecules using bacterial structures such as lipopolysaccharides and capsules thus posing significant challenges in the design of vaccines. This is the reason why the available vaccines are only able to protect people against subsets of the pathogen’s strains. Lo et al. (2009) identified two vaccines that are able to protect people against the widespread serogroup B disease that has posed a significant challenge in the development of vaccines for many years. Regardless of the efforts, it is evident that little information is available on the ways employed by the pathogen to protect itself against the immune system of the host. The figure below shows the micrograph magnification of meningococci.
Figure 1: Micrograph Magnification of Meningococci (Stoddard et al. 2012)
Wang et al. (2016) examined the invasion of the blood-brain barrier by pathogens. The blood-brain barrier (BBB) regulates the traffic of macromolecules to maintain biochemical homeostasis in the tissues of the brain. However, the existence of inter-endothelial junction complexes prevents majority of the macro-organisms to cross the border (Dando et al. 2014). Consequently, meningitis pathogens that intend to cross the border should possess specific traits that permit them to access the blood stream (bacteremia) and cross the border (meningitis) (Wang et al. 2016). S. pneumonia is an exception since it travels from the nasopharynx, evades the defense mechanisms of the host, crosses the border, and survives in the cerebrospinal fluid to cause meningitis. In regard to N. meningitides, also called meningococcus, the pathogen mainly colonizes the nasopharynx with a small proportion of the infection proceeding to a sustained bacteremia. Following its entry into the bloodstream, the pathogen creates a deadly septic shock that enables it to cross the border or invade the meninges.
Bacterial adhesion and crossing the border requires two host receptors: β2-adrenoceptor and CD147. Virtually, the invasion of the meninges is the result of the interaction between brain microvascular endothelial cells (BMEC) and N. meningitidis. Type IV pili intermediates the interaction. The interaction results in the formation of micro colonies on the surface of the endothelial cells. Following the interaction is the activation of signalling pathways within the endothelial cells that results in the formation of endothelial docking structures that are similar to the cells developed from the interaction between BMEC and leukocytes during extravasations (Wang et al. 2016). The result of the signalling events caused by bacteria is the deposition of intercellular junction components in the intercellular junctions and docking structure. The depletion of tight junctions (TJs) results in the formation of para-cellular routes though the border that leads to the brain. Despite the available research on the pathogenesis of N. meningitidis, the pathogenesis of the bacterium should consider the penetration of the pathogen across the border as the most significant areas when dealing with the disease.
An examination of the virulence genes in the pathogen reveals that the invasive and carriage strains belong to specific populations. Consequently, they are transferred genetically from the parent to the offspring. Further research carried out by Coureuil et al. (2012) revealed that the metabolic adaptations allows the pathogen to exploit the resources of the host, thus supporting the idea that virulence genes are an essential capability in the invasion. Coureuil et al. (2012) identified at least four mechanisms through which a microorganism can cross the blood-brain barrier. Transcellular transport enabled by adhesion-induced or passive transcytosis is one of the strategies. The second strategy is para-cellular passage via the opened TJs. Thirdly; microorganisms can also cross the border by causing a direct cytotoxic effect that disrupts the endothelial layer. Finally, infected phagocytes can also facilitate the transport of the organisms across the border.
The four pathways are not exclusive to viruses that penetrate into the CNS using infected leukocytes or by interacting directly with the brain barrier. Extracellular pathogens do not use infected leukocytes to cross the blood-brain border. In addition, the failure of border because of bacterial cytotoxity or apoptosis are also unlikely because haemorrhages and other tissue lesions within the subarachnoidal space are not common during bacterial meningitis. This implies that blood-borne pathogens have to respect the architecture of the blood-brain border before gaining access to the cerebrospinal fluid. The adhesion of the pathogens to the endothelial cells induces an intracellular signalling pathway that disrupts the intercellular tight junctions thus allowing the bacteria to enter the CSF. Alternatively, the pathogen can also induce its own transcytosis via the cell monolayer. Despite the fact that it is possible to internalize N. meningitidis in-vitro within BMEC’s vacuoles, recent studies have also affirmed that the pathogen is able to open gaps in a single layer of the endothelial cells because of the delocalization of tight junctions even in the absence of transcytosis. Therefore, the para-cellular route is the strategy used by N. meningitidis to cross the blood-brain border. Figure 2 below shows the pathophysiology of bacterial meningitis.
Before the bacterium successfully invades the meninges, it should possess several attributes. Firstly, it should be able to survive and grow in the extracellular fluids. The condition is imperative since the level of bacteremia is directly proportional to the meningeal invasion by N. meningitidis. Bacteremia raises the level of the meningeal invasion since it increases the likelihood that the bacterium will interact with the blood-brain barrier. As a result, the attributes of the bacterium that allow it to survive in the extracellular fluid play a crucial role in its ability to invade the meninges. Secondly, the pathogen should also interact with the endothelial cells of the brain for meningeal invasion to occur. The interaction is essential in meningococcal pathogenesis. The flow of blood creates mechanical forces that vary relative to the size of the vessels thus preventing interaction between bacteria and endothelial cells. The finding resulted in a study to investigate the ability of N. meningitidis to interact with endothelial cells despite the existence of mechanical forces created by the blood flow. In the study, Mairey et al. (2006) observed that the adhesion of the pathogen to epithelial cells of the brain was limited to the capillaries of the infected regions where the rate of blood flow if very low. The study affirmed the hypothesis that drag forces determine the attachment or adhesion of bacteria to the endothelial cells.
Figure 2: Pathophysiology of Bacterial Meningitis (Scheld et al. 2002)
The Potential of Using the Knowledge in Treatment
Three main factors determine the vaccine policy for meningitis, just like the other infectious diseases. These include public awareness of the problem, the disease burden, availability of funds to conduct vaccine campaigns, and the availability of the vaccines (Stoddard et al. 2012). The epidemiology of meningitis has exhibited dynamic changes in serogroup incidences between different geographical regions and over time. The emergence of hyper-virulent strains has also caused unpredictable outbreaks. The majority of the global meningitis burden emanates from the six serogroups: A, B, C, X, Y, and W-135. Researchers have already developed conjugate vaccines for subgroups A, C, Y, and W-135. Routine vaccinations using the conjugates of serogroup C have been effective in reducing the asymptomatic carriage and incidence of the disease thus resulting in herd protection. The future of controlling the incidence of the disease depends on the continued use of pathogen-specific vaccinations and treatments to prevent and manage the disease respectively.
The best preventative interventions include immunization against rare diseases and vaccinating large groups of the population to create herd immunity. The fluctuations in the incidence of the disease necessitate continuous surveillance in identifying, understanding, and forecasting changes in the epidem...