Introduction
Bacterial meningitis is an infection that affects the meninges, the cerebrospinal fluid and the spinal cord that causes death and disability in a number of people worldwide. This is a highly contagious airborne disease that is spread through the transmission of three organisms present in the respiratory secretions: Neisseria meningitides, Haemophilus influenzae, and Streptococcus pneumoniae. The onset or origins of the disease varies among different age groups and geographic locations. According to estimates, 200,000 people die annually of meningitis. Case fatality rates vary with age at time of illness and also depend on the particular bacterial strain causing the infection (Parke, Schneerson and Robbins, 1972). The fatality rates are between 3 and 19% in developed countries while in most developing countries this rate is much higher ranging between 37 to 60% (Zaidi et al., 2005). Among those who survive, 54% are left with permanent disabilities such as deafness, blindness, mental retardation, and several neurological complications (Koomen et al., 2003).
In the United Kingdom, around 900 cases of bacterial meningitis are reported every year due to N meningitides and S pneumoniae and around 500 reported due to meningococcal septicaemia. However, the introduction of specific vaccines has dramatically reduced the number of cases reported every year. Although conjugate pneumococcal vaccines have shown positive results in children, their ability in preventing outbreaks in adults still remains unclear. Thus, it is necessary to remain careful about the possibility of cases of meningitis and septicaemia.
Most Significant Bacteria
The distribution of meningitis causing bacteria are shown in the chart below following a detailed description.
- Neisseria meningitides
Among different possibilities, two overlapping conditions of meningitis, meningitis and bloodstream infection (meningococcaemia), are caused due to N. Meningitides infections (Stephens, Greenwood and Brandtzaeg, 2007). It is possible for these two syndromes to occur simultaneously. However, it is meningitis that occurs most frequently in patients. The bacterium N meningitidis is classified into serogroups based on the immunological reactivity to the polysaccharide. This has resulted in 13 such serogroups among which groups A, B, and C account for 90% of all the meningitis related infections. Meningococcal disease is the most dangerous of all the other kinds of meningitis because of its ability to cause widespread epidemics.
Certain parts of sub Saharan Africa is generally referred to as the meningitis belt due to its high periodic epidemic rate (Molesworth et al., 2002). When the epidemic strikes, about one in a hundred people of the population are affected by the disease which is 100 times more severe than the sporadic disease. Among different age groups in this region, children under the age of 2 are the most affected by the disease (Moore, 1992).
- Haemophilus influenzae
Meningitis caused by H influenzae spread particularly rapidly in children under the age of 5 due to organisms which contain the polysaccharide b capsule (Hib). These are airborne diseases and are usually contracted through respiratory routes. These bacteria stick to the epithelial cells of the upper respiratory tract and colonize the nasopharynx. After acquiring the bacteria, the disease is caused when the organism penetrates the respiratory mucosa and enters the bloodstream. Numerous factors contribute to the entry of the organism into the bloodstream through which it eventually gains access to the cerebrospinal fluid where, once the infection is established, inflammation occurs (Schreiber et al., 1986). Meningitis is the most important and severe of all Hib diseases and causes death in most cases due to secondary infections such as pneumonia.
- Streptococcus pneumoniae
The meningitis causing bacteria are age and blood health specific. In infants, young children and the elderly, meningitis is caused by the S pneumoniae bacterium. In young adults with haemoglobinopathies such as sickle cell disease or any other anatomic asplenia are more susceptible to contracting S pneumoniae. Just like other Hib infections, S pneumoniae is contracted through air. After the bacteria colonize the nasopharynx, the illness occurs when the bacteria attack the mucosal defence and enter the bloodstream through which it reaches the meninges and the cerebrospinal fluid. The risk of spreading the disease in all cases of meningitis is extremely high, particularly among close contacts such as family members, or those who are in direct contact with the patient’s oral secretions. Most cases of deaths are caused by the pneumococcal pneumonia, even though pneumococcal meningitis is the most severe manifestation of pneumococcal disease.
Although any bacteria contracted environmentally have the potential of causing meningitis, most of the bacterial meningitis cases are attributed to S pneumoniae, N meningitidis, and H influenzae of Hib type b. As mentioned earlier, numerous factors such as age group, environmental conditions, season, geographic locations, etc. affect the severity of the outbreak. This can be understood by analyzing the sudden outbreak in meningococcal meningitis during the dry winter in some parts of the United Kingdom. The dryness of the weather and the strong winds caused the disease to spread more rapidly. We will now discuss how the different strains of bacteria affect different age groups. The seasonal variation of meningitis in the UK is shown in Fig 2.
Neonatal Meningitis - Demographic Variations
Neonates or infants are highly susceptible to contracting meningitis due to their underdeveloped immune system. A study has even shown that in developed countries such as in the UK, the occurance of neonatal meningitis in 0.3 in every 1000 births (Harvey, Holt and Bedford, 1999). In some parts of Asia and Africa, this number is much higher at 6.1 for every 1000 births. Even though in these cases, the mortality rates are as low as 10%, long term neurological complications are the source of major concern (Klinger et al., 2000). The organism responsible for most neonatal meningitis cases is the group B streptococci which is responsible for almost half of all the cases. Another organism that causes neonatal meningitis is gram negative enteric rods such as E coli which are isolated in 20% cases. Among 5 to 10% of reported cases are due to the L monocytogenes (Zaidi et al., 2009). In developing countries the effects of Gram negative rods such as E coli and K pneumoniae are significantly higher than other pathogens. There has been a recent reduction in the number of cases attributed to B streptococci due to the introduction of the antibiotic prophylaxis given pre partum to the infants at risk.
Other cases of bacterial meningitis are caused by Staphylococcus aureus, Pseudomonas aeruginosa and a few strains of enterococci. These forms of meningitis are usually contracted due to nosocomial infections that occur, usually, after any trauma or surgery. However, with the development of new kinds of antibiotics and intervention methods, these forms are rapidly decreasing.
Pathophysiology or Mechanisms of Bacterial Meningitis
Most cases of meningitis are a consequence of inflammation caused as a defence against the invading bacterium. This inflammatory response can be either acute or chronic depending on the pathogen causing the meningitis. The entry of the bacteria into the bloodstream is the primary step in the development of meningitis. Another method through which the disease can be contracted is by direct invasion of the central nervous system which may be caused by problems in the dural matter or by the direct infection of the central nervous system. In a few patients, the pathogen reaches the central nervous system through infection of the sinuses or the internal ear. But, the most severe cases of meningitis are caused by bacteremia, or the bacterial invasion of the bloodstream.
It is, however, unknown the exact location from which the bacteremia occurs. Some assume that the choroid plexus is associated with transmission. This assumption was based on the observation made by Daum et al, who in 1978 demonstrated the transmission of H influenzae through the choroid plexus (Daum et al., 1978). With the development in medical imaging and laboratory techniques, certain other access points to the central nervous system have also been identified. Research has revealed the existence of meningococci bacteria in the meninges along with the choroid plexus. Studies have also documented the infiltration of the leptomeningeal vessels by pneumococci bacteria (Zwijnenburg et al., 2001).
The blood brain barrier is, usually, strong enough to prevent bacterial infections of the brain and the central nervous system (CNS). Thus, breaching this barrier is a crucial task for the bacteria to gain entry into the CNS. This is done when the bacteria make use of certain proteins which exist on the surface of the bacteria that eventually help in breaching this barrier. These proteins are Streptococcal proteins, meningococcal adhesin, outer membrane proteins, etc. which help in bacterial adhesion and the endocytosis that follows as a result. These protiens have also been found in GBS and E coli bacteria which cause meningitis in newborn children. The age-wise distribution of bacterial meningitis is shown in figure 3.
Inflammation
When the bacteria invade the body, the initial response is the inflammation of the endothelial cells. This response induces a leukocyte infiltration which is a process that involves a number of steps beginning with the build up of leukocytes especially the granulocytes. Thus, the presence of granulocytes in the cerebro spinal fluid is an important disagnosis in bacterial meningitis. The methodology of bacterial attack and aggravation appear to happen parallel, with the latter aiding the previous by expanding the penetrability of the blood brain barrier.
The results of leukocyte enactments which incorporate the network metalloproteinases, nitric oxide and others influence the barrier and the blood-cerebrospinal fluid obstruction by making it break (Kieseier, 1999). This gives microbes the chance to penetrate the hindrance and addition section into the CNS. Once inside the sub-arachnoid space, the microorganisms repeat. The increment in number of microscopic organisms alongside their autolysis upgrades the procedure of irritation which is the premise of pathogenesis of bacterial meningitis.
The inflammatory reaction to the microorganisms is a complex methodology including a mixture of inflammatory cells prominently endothelial cells, mast cells and perivascular macrophages. Bacterial parts equipped for actuating host inflammatory reaction incorporate peptidoglycans, lipoprotein, lipopolysaccharides and lipoteichoic corrosive. Tests demonstrated that their capability to 10 trigger the incendiary middle people stays unaltered regardless of the possibility that hotness eliminated microbes are vaccinated into the host (Polfliet et al., 2001).
Neuronal Damage
Bacterial meningitis has a high occurrence of neurological difficulties with very nearly half of the patients demonstrating neurological deficiencies to differing degree (de Beek et al., 2002). The neuropathy results from the inflammation of the subarachnoidal space, vasculitis and edema of the brain tissue. Neuronal trauma to the cerebral cortex, hippocampus and inner ear are additionally a paramount reason for the majority of the intricacies (Roos and Tunkel, 2010). The damage brought on to the central nervous system by the attacking microbes is credited to different components, for example, bacterial poisons, the incendiary reaction to the attacking living being or the cytotoxic components of the supplement framework.
Notwithstanding these elements, the circuitous impact of these intracranial complications on the encompassing structures of the CNS is in charge of the indications because of the "space occupying lesions" effect that goes hand in hand with meningitis. The bacterial toxins for S. pneumoniae include pneumolysin, which is a pore structuring cytolysin and hydrogen peroxide (Braun et al., 2007). The pneumolysin specially influences the mitochondrial film creating the harm by righteousness of its pore structuring action. The key destructiveness elements for N. meningitidis and other related gram negative microorganisms are the lipopolysaccharides and lipooligosaccharides. These endotoxins trigger the arrival of interleukin-6 and tumor necrosis factor alpha (TNF ) alongside different cytokines mediators. These mediators are responsible for tissue or organ damage and consequently the manifestations that are normal for bacterial meningitis.
Clinical Diagnosis
Clinical evaluation of seriousness of bacterial meningitis is significant for recognizing the elements that influence bacterial meningitis. Most regular signs incorporate the "usual triad" of fever, headache and neck solidness. However, these established indications happen in less than 50% of the cases. Typically, the manifestations are non-specific appearing early in the process of the illness with fever, headache and discomfort as the fundamental symptoms. Particular indications for example, neck stiffness, photophobia and impairment of awareness indicate meningeal disturbance and manifest later as the ailment advances (van de Beek et al., 2004). Indications of meningeal aggravation help fundamentally to the determination of bacterial meningitis, all the more so in the settings without cutting edge 11 day research center offices. Yet these signs may not be available in unaware patients, children or in the immunocompromised patients. Such cases may display as a symptomatic challenge. Different indications that may go hand in hand with bacterial meningitis incorporate nausea, regurgitating, back rigidity, seizures, shock, black outs and bleeding from skin. Petechial rash is another improtant vharacteristic for disease by N. meningitidis and speak to meningococcemia.
In the developing nations with meagre research facilities these clinical indications structure the standard for the diagnosis of bacterial meningitis. Owing to the significance of these clinical symptoms numerous studies were directed to understand the occurrence of the different basic signs and symptoms of bacterial meningitis. the outbreak of bacterial meningitis in the UK has drastically changed in the past few decades since the intervention of vaccines for Hib, serogroup C meningococcus and a few strains of pneumococcus. Since there are no current vaccine against serogroup B meningococcus, this strains is the most potent one that is responsible for most meningitis outbreaks in children aged 3 months or older (Visintin et al., 2010).
After Effects of Bacterial Meningitis
If the disease is left untreated, bacterial meningitis can result in different complications like listening hearing impairments, speech irregularities, intellectual underdevelopment, learning difficulties and seizures. The rate of these complications can be as high as even half of all diagnosed cases. The possibilities of contracting these complications build depending on the bacteria under consideration, age of the patient, the seriousness of ailment and the nature of treatment gave. These complexities are more basic in children and can result in genuine neurological issues that regularly have a tendency to be long term. Included among these complexities are focal neurological deficits, for example, paralysis of the limbs, developmental incapacities, seizures, cerebral abscesses and hydrocephalus. A large portion of these complexities in children generally resolve inside 2-3 years yet 10% of the children might create complications that continue for the duration of the life.
Risk Factors and Treatment of Bacterial Meningitis
The development of antibiotics has radically enhanced the result of bacterial meningitis. Launch of proper treatment within 6 hours of presentations decreases the death rates by more than 8 times. Any delay in the start of antibiotic treatment is shown to be the absolute most significant risk component attributed to the result of bacterial meningitis. The European Federation of Neurological Societies (EFNS) taskforce on bacterial meningitis strongly suggests start of antibacterial treatment inside the first hour of diagnosis. The common treatment is with a wide range third generation cephalosporin which is normally given experimentally while the lab results are anticipated.
As of now two sorts of vaccines are generally utilized against different serotypes of N. meningitidis: pure polysaccharide vaccines and conjugate vaccines. The conjugate vaccines are considered better than the polysaccharide vaccines as the latter is known to be less immunogenic in children what's more gives just a makeshift protection going from three to five years. Both pure polysaccharide and conjugate vaccines against serogroups A, C, Y and W135 have been created. Conjugate vaccines against the serogroup C is currently consistently utilized as a part of routine adolescence inoculation plans in some European nations. The vaccines has moreover brought about a critical decrease in the nasopharyngeal carriage rates of serogroup C. Advancement of a vaccine against serogroup B has experienced troubles because of poor immunogenic nature of the polysaccharide capsule. This has prompted the improvement of vaccines focusing on different structures, for example, the outer membrane vesicle (OMV) vaccines. Achievement has been reported with the utilization of OMV vaccines in New Zealand with a general viability extending between 70-80% (93). With the achievement of OMV vaccines against serogroup B, prospects of creating a comparable outer membrane vesicle vaccine against different sergroups, for example, serogroup An and W135 are additionally in progress.
References
Amsalu, S. and Assefa, A. (2005). Meningitis in children beyond the neonatal period in Gondar University hospital. Ethiopian medical journal, 43(3), pp.175-180.
Braun, J., Hoffmann, O., Schickhaus, M., Freyer, D., Dagand, E., Bermpohl, D., Mitchell, T., Bechmann, I. and Weber, J. (2007). Pneumolysin Causes Neuronal Cell Death through Mitochondrial Damage. Infection and Immunity, 75(9), pp.4245-4254.
Braun, J., Hoffmann, O., Schickhaus, M., Freyer, D., Dagand, E., Bermpohl, D., Mitchell, T., Bechmann, I. and Weber, J. (2007). Pneumolysin Causes Neuronal Cell Death through Mitochondrial Damage. Infection and Immunity, 75(9), pp.4245-4254.
Daum, R., Scheifele, D., Syriopoulou, V., Averill, D. and Smith, A. (1978). Ventricular involvement in experimental Hemophilus influenzae meningitis. The Journal of Pediatrics, 93(6), pp.927-930.
de Beek, D., Schmand, B., de Gans, J., Weisfelt, M., Vaessen, H., Dankert, J. and Vermeulen, M. (2002). Cognitive Impairment in Adults with Good Recovery after Bacterial Meningitis. The Journal of Infectious Diseases, 186(7), pp.1047-1052.
Harvey, D., Holt, D. and Bedford, H. (1999). Bacterial meningitis in the newborn: A prospective study of mortality and morbidity. Seminars in Perinatology, 23(3), pp.218-225.
Kieseier, B. (1999). Differential expression of matrix metalloproteinases in bacterial meningitis. Brain, 122(8), pp.1579-1587.
Klinger, G., Chin, C., Beyene, J. and Perlman, M. (2000). Predicting the Outcome of Neonatal Bacterial Meningitis. PEDIATRICS, 106(3), pp.477-482.
Koomen, I., Grobbee, D., Roord, J., Donders, R., Jennekens-Schinkel, A. and van Furth, A. (2003). Hearing Loss at School Age in Survivors of Bacterial Meningitis: Assessment, Incidence, and Prediction. PEDIATRICS, 112(5), pp.1049-1053.
Molesworth, A., Thomson, M., Connor, S., Cresswell, M., Morse, A., Shears, P., Hart, C. and Cuevas, L. (2002). Where is the meningitis belt? Defining an area at risk of epidemic meningitis in Africa.Transactions of the Royal Society of Tropical Medicine and Hygiene, 96(3), pp.242-249.
Moore, P. (1992). Meningococcal Meningitis in Sub-Saharan Africa: A Model for the Epidemic Process. Clinical Infectious Diseases, 14(2), pp.515-525.
Parke, J., Schneerson, R. and Robbins, J. (1972). The attack rate, age incidence, racial distribution, and case fatality rate of Hemophilus influenzae type b meningitis in Mecklenburg County, North Carolina. The Journal of Pediatrics, 81(4), pp.765-769.
Polfliet, M., Zwijnenburg, P., van Furth, A., van der Poll, T., Dopp, E., Renardel de Lavalette, C., van Kesteren-Hendrikx, E., van Rooijen, N., Dijkstra, C. and van den Berg, T. (2001). Meningeal and Perivascular Macrophages of the Central Nervous System Play a Protective Role During Bacterial Meningitis. The Journal of Immunology, 167(8), pp.4644-4650.
Roos, K. and Tunkel, A. (2010). Bacterial infections of the central nervous system. Edinburgh: Elsevier.
Schreiber, J., Barrus, V., Cates, K. and Siber, G. (1986). Functional Characterization of Human IgG, IgM, and IgA Antibody Directed to the Capsule of Haemophilus influenzae Type b. Journal of Infectious Diseases, 153(1), pp.8-16.
Stephens, D., Greenwood, B. and Brandtzaeg, P. (2007). Epidemic meningitis, meningococcaemia, and Neisseria meningitidis. The Lancet, 369(9580), pp.2196-2210.
Stephens, D., Greenwood, B. and Brandtzaeg, P. (2007). Epidemic meningitis, meningococcaemia, and Neisseria meningitidis. The Lancet, 369(9580), pp.2196-2210.
Unkmeir, A., Latsch, K., Dietrich, G., Wintermeyer, E., Schinke, B., Schwender, S., Kim, K., Eigenthaler, M. and Frosch, M. (2002). Fibronectin mediates Opc-dependent internalization of Neisseria meningitidis in human brain microvascular endothelial cells. Molecular Microbiology, 46(4), pp.933-946.
van de Beek, D., de Gans, J., Spanjaard, L., Weisfelt, M., Reitsma, J. and Vermeulen, M. (2004). Clinical Features and Prognostic Factors in Adults with Bacterial Meningitis. New England Journal of Medicine, 351(18), pp.1849-1859.
Visintin, C., Mugglestone, M., Fields, E., Jacklin, P., Murphy, M. and Pollard, A. (2010). Management of bacterial meningitis and meningococcal septicaemia in children and young people: summary of NICE guidance. BMJ, 340(jun28 1), pp.c3209-c3209.
Zaidi, A., Huskins, W., Thaver, D., Bhutta, Z., Abbas, Z. and Goldmann, D. (2005). Hospital-acquired neonatal infections in developing countries. The Lancet, 365(9465), pp.1175-1188.
Zaidi, A., Thaver, D., Ali, S. and Khan, T. (2009). Pathogens Associated With Sepsis in Newborns and Young Infants in Developing Countries. The Pediatric Infectious Disease Journal, 28(Supplement), pp.S10-S18.
Zwijnenburg, P., van der Poll, T., Florquin, S., van Deventer, S., Roord, J. and van Furth, A. (2001). Experimental Pneumococcal Meningitis in Mice: A Model of Intranasal Infection. The Journal of Infectious Diseases, 183(7), pp.1143-1146.
