Cognitive and Physical Effects of Bacterial Meningitis: Difference between revisions

Latest revision as of 01:09, 30 April 2024

Introduction

The bacterium shown above is called meningococcus which causes meningococcal meningitis.^[1] Photo credit [1]

By Alyssa Gest

Meningitis, characterized by the inflammation of the meninges surrounding the brain and spinal cord, poses a significant threat to human health, especially acute bacterial meningitis ^[2]. Understanding the etiology and virulence factors of bacterial meningitis is crucial for prevention, diagnosis, and treatment. Such pathogens include Streptococcus pneumonia, Neisseria meningitidis, Haemophilus influenza, and Listeria monocytogenes ^[3] They demonstrate various mechanisms to break through the blood-brain barrier and invade the central nervous system^[4]. These lead to altercations in the brain and spinal cord and later the infected person can develop cognitive impairment and physical consequences. These mechanisms enable bacterial colonization inside the hose cell and promote their survival. They also involve complex interactions with the virulence factors of the pathogenesis bacteria and the host cell immune mechanisms.^[4] These processes help scientists and doctors develop targeted therapies and vaccines for bacterial meningitis.

Background

Historical Perspective

Evidence of central nervous system (CNS) infections are one of the oldest infections known in mankind^[5]. In the 17th and 18th centuries, brain fever was frequently referred to as “phrenitis” and “cephalitis” which today, is classified as meningitis. These patients reported symptoms like headaches, fever, and delirium^[6]. The clinical characterization of meningococcal disease outbreak was first found in Genvea in 1805, by a general practitioner, Gaspard Vieusseux^[7]. The initial occurrence in Africa was documented in 1840 but it was not identified as meningococcal bacteria as the causative agent of meningitis by Austrian bacteriologist Anton Vaykselbaum ^[7].

Pathophysiology of Bacterial Meningitis

Labeled illustration of the layers surrounding the brain, the dura mater, arachnoid, and pis matter.^[8] Photo credit [2]

The meninges, consisting of three protective layers surrounding the brain and spinal cord, play a vital role in guarding these organs while providing nourishment and support^[9]. The meninges contain three layers, the outer layer is called the dura mater, the middle layer is the arachnoid mater, and the inner layer is called the pia mater (the arachnoid mater and pia mater are the leptomeninges)^[9]. Between the leptomeninges is a space called the subarachnoid space which holds cerebrospinal fluid (CSF)^[9]. It is a clear water fluid that is pumped around the brain and spinal cord, to protect them from impact/contact and contains nutrients^[9]. The CSF is held under some pressure, below 200mm of water which is less than ⅕ of the mean arterial pressure^[9]. There is about 150mL of CSF in the body which is constantly refilled with 500mL of new fluid every day and the excess is absorbed into the bloodstream (350mL)^[9]. For nutrients to enter and exit the CSF/brain, they have to go through the stringently controlled blood-brain barrier^[9]. The endothelial cells in the blood vessels are so tightly packed next to each other that they prevent leakage and only allow specific molecules to pass through^[9]. This is the same concept as the phospholipid bilayer in eukaryotic cells. Inflammation occurs in the leptomeninges, not the brain itself (which is called encephalitis). However, these can occur at the same time which is referred to as meningoencephalitis ^[9].

Attachment and Invasion

To facilitate adhesion and break through the barriers surrounding the brain, a certain level of bacteria in the bloodstream is required which is linked to how severe the infection is^[10].Direct invasion through the tissues is possible as well^[10] . Bacterial adhesion involves multiple adhesion molecules from the pathogen that interact with the target receptors of the host cells^[10]. The initial interactions can trigger the expression of further host receptors which can be targeted by other bacterial adhesions^[10]. Pathogens tend to bind to extracellular matrix proteins to facilitate initial attachment to the host cells^[10]. By binding to a specific host cell receptor, it can induce different signal transduction pathways to promote attachment to the internalization of the bacteria into the host cells^[10]. Firbrils and pili are used for the invasion of human brain microvascular endothelial cells(HBMECs) which makes them very important virulence factors for the entry of the CNS^[10].

There are two mechanisms for endocytosis of pathogens into non-phagocytotic cells. These include the “zipper” and “trigger mechanism”^[10].The “zipper” mechanism is the interaction of a bacterial ligand and a host-specific membrane receptor initiating signals that lead to the pathogen entering the cell via endocytosis^[10]. The “trigger mechanism” is a micropinocytosis process that involves the formation of actin-rich membrane ruffles^[10].These structures are created by specific changes in actin dynamics and membrane remodeling, prompted by the injection of active effectors through a needle-like structure called a type three secretion system (T3SS) into the host cell cytosol, which then initiates signaling cascades^[10].

Entry Into the CNS

Meningitis-causing pathogens usually cross host barriers through transcellular or paracellular ways^[10]. Transcellular traversal is when a pathogen crosses the cell barrier without tight junction disruption or traversal between cells^[10]. This is done by invading the barrier and manipulating signaling pathways^[10]. Another form is paracellular traversal which involves penetration of pathogens between the host’s cells and can occur with or without disrupting the tight junctions^[10]. The release of bacterial toxins also can disrupt the barrier function and advance paracellular traversal^[10].

The bacteria can utilize the host cell’s signaling molecules to facilitate their infection. To enter and leave the host cells, pathogens have evolved mechanisms that use actin polymerization machinery that belongs to the host cell^[10]. They also use different signal-transduction mechanisms that rearrange the actin cytoskeleton which allows the pathogen to initiate attachment and enter the host cell, moving in and around the cell thus forming vacuoles^[10]. The immune system of the host can be activated by these molecules and these pathogen-associated molecular patterns (PAMPs) are recognized by eukaryotic pattern recognition receptors (PRRs), which induce signaling cascades such as mitogen-activated protein kinase and the nuclear factor-kB^[10]. Activating these pathways causes pro-inflammatory reactions like increased regulation of cytokines^[10].

Pathogen Survival

Extracellular replication is the most common process for pathogenic bacteria to spread and survive^[10]. These bacteria have to overcome cellular defense mechanisms by the host cell such as the upregulation and secretion of neutrophil-specific factors in HBMECs^[10]. This brain-blood barrier response is supposed to recognize pathogens resulting in their clearance but overaction of the cellular response through continuous exposure to the pathogens could cause an increase in inflammation and compromised barrier function^[10].

Virulence Factors

Virulence factors that are used by gram-positive and gram-negative bacteria include adhesions and internalins, pore-forming toxins, and factors that promote intracellular movement and cell-to-cell spread^[10]. Streptococcus pneumonia, Neisseria meningitidis, and Haemophilus influenza all produce a polysaccharide capsule that helps them invade the host without any damage and resist phagocytosis^[10]. Surface proteins like adhesions allow the pathogen to attach to the host cells and endotoxins are possessed by gram-negative bacteria like N. meningitidis, E.coli, S. pneumonia, and H. Inflenzae which induces inflammation and tissue damage^[10].

What Triggers Inflammation?

Graphic showing a brain with normal meninges compared to a brain with inflamed meninges.^[11] Photo credit [3]

It can be caused by an autoimmune disease, where the body attacks itself or the body could experience an unfavorable reaction to a certain medication^[9]. This can occur during intrathecal therapy (medication is injected directly into the CSF)^[9]. The most common way of contracting the disease is by infection across all ages (ex. Neisseria meningitidis bacteria or herpes simplex virus)^[9]. There are two routes the infection can take to reach the leptomeninges and the CSF. The first route is direct spread, which is when the pathogen gets inside the spinal column or skin and then penetrates the meninges, leading into the CSF^[9]. The pathogen will either come through the skin or up the nose^[9]. The second route is through hematogenous spread, which is when the pathogen enters the bloodstream and moves through the endothelial cells in the blood vessels making up the blood-brain barrier and entering the CSF^[9]. Bacteria will do this by binding to surface receptors on the endothelial cells to get across the barrier^[9]. If not, they will find other areas to damage like the choroid plexus^[9]. Once it enters the CSF, it can start replicating and spreading. The white cells will eventually detect the pathogenic cells and send cytokines to bring in more immune cells^[9]. Over time, the concentration of white blood cells in a microliter of cerebrospinal fluid (CSF)can increase to thousands^[9]. However, exceeding five cells typically indicates meningitis^[9]. In bacterial infections, the count usually surpasses 100 cells per microliter, with more than 90% being polymorphonuclear leukocytes (PMNs)^[9]. Viral meningitis is usually present with 10-100 white blood cells per microliter (consisting of over 50% lymphocytes and fever than 20% PMNs)^[9]. Fungal meningitis typically exhibits 10-500 white blood cells with lymphocytes accounting for over 50%^[9]. In tuberculous meningitis, white blood cell count ranges from 50-500 cells per microliter (lymphocytes constituting over 80%). The pressure from the additional immune cells will most likely rise above 200 nm of water^[9]. The immune system will also induce the glucose concentration to drop in the CSF, up to below 2 ⁄ 3 of the concentration in the blood, making the protein levels increase to over 50 mg/dL^[9] .

Causes and Risk Factors

Age

Everyone is susceptible to catching bacteria meningitis. However, multiple pathogens infect certain age groups more than others. Infants are most likely infected by Group B streptococcus (ex. Streptococcus agalactiae), gram-negative enteric organisms (ex. E.coli), and Listeria monocytogenes (L. monocytogenes)^[12]. 1 to 23 month olds are susceptible to Streptococcus pneumonia (S. pneumonia), Neisseria meningitidis (N. meningitides), S. agalactiae, Haemophilus influenzae (H. influenza), and E.coli^[13]. Children and teens are most likely infected with N. meningitidis and S. pneumonia ^[9]. Those who are adults and elderly will most likely contract S. pneumonia, and L. monocytogenes ^[9]. If you are over 50 years of age, N. meningitidis is also likely as well^[14].The immunocompromised status of the infected patient is also an important factor to consider for the rate of survival^[15].

Bacterial Families

Magnified images of different bacteria that cause meningitis.^[16] Photo credit [4]

As previously mentioned, multiple bacteria can cause bacterial meningitis. Some examples are Group B Streptococcus, E.coli, H. Influenza, M. tuberculosis, S. pneumonia, and N. meningitidis ^[17]. Group B Streptococcus measures between 0.5-1.25 micrometers ^[18], E.coli measures between 1.0-2.0 micrometers long ^[19], H.influenzae measures between 0.3-1 mircrometers ^[20], S. pneumonaie measures between 0.5-1.25 micrometers long^[21]. Bacterial meningitis can spread through various ways, depending on the bacteria causing the infection. Some individuals will not experience symptoms, but will still be "carriers" of that bacteria that can still be spread to those around them^[22]. For instance, Group B Streptococcus and E.coli are usually passed from the mothers to newborns during childbirth^[22]. H. influenza, M. tuberculosis, and S. pneumonia are typically transmitted through respiratory droplets through coughing and sneezing during close contact interactions^[22]. N. meningitidis, however, spreads through the sharing of respiratory or throat secretions such as saliva or split, which occurs through living in the same proximity, kissing, and coughing^[22]. E.coli can be transmitted through food consumption or by the preparation of the food^[22]

Symptoms and Diagnosis

Symptoms

Meningitis displays a variety of symptoms and is usually characterized by a sudden onset of fever, stiff neck, and headache ^[17]. Individuals may also experience sensitivity to light (photophobia), nausea, vomiting, and altered mental status (ex. confusion)^[17]. Some may also experience phonophobia which is displaying discomfort due to loud noises^[9]. However, newborns and babies may not have these more common symptoms but rather show different signs. These include feeding poorly, irritability, slow/inactive movements, vomiting, abnormal reflexes, or a bulging fontanelle that will form on the baby's skull ("soft spot")^[17].

A diagram of a lumbar puncture being inserted into the subarachnoid space between L3 and L4.^[23] Photo credit [5]

Diagnosis

The first step for assessing for potential signs of meningitis begins with a comprehensive physical exam ^[9].The patient will be positioned flat on their back and undergo specific movements to see how the patient responds^[9]. One example is raising one leg with the knee flexed at a 90-degree angle, gradually straightening it at the knee^[9]. If back pain is present, it is known at Kernig's sign^[9]. Another example involves the patient lying supine with their neck supported and flexed; if their knee/hip reflexively flexes, it indicates Brudzinski's sign^[9]. If meningitis is suspected, a lumbar puncture is performed; Doctors will also collect blood and cerebrospinal fluid samples and evaluate them in a lab to trace the exact cause ^[9] ^[17]. This involves inserting a needle through the lower lumbar vertebrae (usually between L3 and L4), to access the subarachnoid space^[9]. A small amount of cerebrospinal fluid (CSF) is extracted to access white blood cells, glucose, and protein levels ^[9]. Polymerase chain reaction (PCR) is then utilized to detect specific pathogens that are causing the infection or disease^[9]. If the infection is identified, a western blot or thin blood smear may be employed to confirm the pathogen^[9].

Treatment and Prevention

Treatment

Penetration across the blood-brain barrier is important for successful treatment. However, this is influenced by the degree of barrier disruption caused by inflammation, as well as antibiotic size, charge, lipophilicity, protein-binding capacity, and interaction with the efflux pumps ^[24]. In bacterial meningitis, a mili-pronged approach is usually the recommended option by doctors^[25]. Administering steroids before antibiotics is a common strategy for mitigating potential extensive damage to the leptomeninges caused by inflammation while antibiotics target the bacteria^[25]. Once the causing pathogen is identified, therapy may be determined. For infections caused by S. pneumoniae, penicillin G it ampicillin monotherapy is often recommended^[26]. Adjunctive treatments may include rifampicin, which exhibits good CSF penetration but could lead to rapid resistance if it's used alone. An anti-inflammatory corticosteroid, dexamethasone, is sometimes added to treatment plans^[27]. However, it might reduce the penetration of antimicrobials into the CSF in the absence of meningeal inflammation. Some clinicians recommend incorporating rifampicin into empirical antimicrobial treatment alongside dexamethasone^[28].

Vaccines

Three vaccines target the most common microbial etiologies of bacterial meningitis: S. pneumoniae, H. influenzae, and N. meningitidis^[29]. The Hib vaccine, which protects against H. influenzae type b, is recommended for children^[29]. The heptavalent pneumococcal conjugate vaccine is also recommended as part of childhood immunizations for children ages 2 to 23 months^[30]. The third vaccine, known as the 23-valent pneumococcal polysaccharide vaccine, is recommended for ages 2 years and older particularly those with chronic health issues, immunocompromised status, anatomic or functional asplenia, those on long-term steroids, or individuals 65 and older^[30].

Cognitive Impairment

The impact of bacterial meningitis can extend far beyond the acute phase. Short and long-term complications pose significant challenges to those infected, particularly in low- and middle-income countries where access to health care is limited^[2].

Short-Term Complications

Subdural effusions, characterized by the collection of fluid between the brain's surface and the dura mater, are common in children, ranging from 20-39%^[2]. This condition usually affects infants (>1 year old)^[2]. While most subdural effusions remain asymptomatic, the infection can lead to neurological damage and a drainage procedure may be performed^[2]. Additionally, focal neurological deficits occur in 3-14% of bacterial meningitis cases^[2]. These deficits, often stemming from ischemic stroke or other intracranial complications, usually exhibit gradual improvement over months to years^[2]. Surgical drainage of abscess collections can relieve some symptoms, although focal deficits resulting from ischemic events may require more recovery time^[2].

Long-Term Complications

Hearing loss has been reported as the most common complication of bacterial meningitis^[2]. This results from both the direct spread of bacteria and the inflammatory response initiated within the meninges and CSF^[2]. Upon reaching the cochlea, the labyrinth (a structure within the inner ear) undergoes inflammation, causing the breakdown of the blood-labyrinth barrier^[2]. Approximately 10% of children affected by bacterial meningitis experience hearing impairment. The consequences of hearing loss can potentially cause speech and language delays as a youth and later influence behavioral changes ^[2].

Patients with one or more abnormal cognitive test results across different domains.^[31] Photo credit [6]

Cognitive Status in Adults After Infection

The rates of cognitive impairment worldwide are hard to estimate because there is no method of measuring and determining long-term data on meningitis survivors(not many survivors to analyze)^[2]. However, in a study from 2007, researchers analyzed cognitive data of 155 adults surviving bacterial meningitis; 79 after pneumococcal and 76 after meningococcal meningitis (N. meningitidis) and 72 healthy individuals^[32]. They found that 32% of patients had cognitive impairment and it was similar to survivors of both pneumococcal and meningococcal meningitis^[32]. However, those who had pneumococcal meningitis performed worse on memory tasks and were relatively slower than meningococcal meningitis^[32]. There was a positive correlation between time since meningitis and self-reported physical impairment^[32]. This study shows that there is a high risk of cognitive impairment associated with bacterial meningitis.

Conclusion

Bacterial meningitis remains a formidable challenge in healthcare and it is one of the oldest known infections of mankind. The causative agents, including S. pneumonia, H.influenzae, and N. meningitidis have distinct characteristics and transmission routes contributing to the complexity of the disease. Understanding the pathophysiology of bacterial meningitis and the intricate mechanisms of invasion helps advance the treatment for these infections. Diagnosis and treatment strategies have evolved, emphasizing recognition, antibiotic therapy, and supportive care. Vaccination is crucial for prevention, as it targets the most common microbial etiologies of bacterial meningitis. However, challenges are still prevalent, including antibiotic resistance, variability in clinical presentation, and the impact of neurological complications on patients. Further research and public health efforts are important for fighting against the pathogens that cause meningitis and improving the outcome of patients.

References

↑ “Bacterial Meningitis: Symptoms, Causes, and Treatment.” Medical News Today. Accessed April 14, 2024. https://www.medicalnewstoday.com/articles/9276#symptoms.
↑ ^2.00 ^2.01 ^2.02 ^2.03 ^2.04 ^2.05 ^2.06 ^2.07 ^2.08 ^2.09 ^2.10 ^2.11 ^2.12 Zainel, Abdulwahed, Hana Mitchell, and Manish Sadarangani. 2021. "Bacterial Meningitis in Children: Neurological Complications, Associated Risk Factors, and Prevention" Microorganisms 9, no. 3: 535. https://doi.org/10.3390/microorganisms9030535
↑ Mehlhorn, Allana, and Brandon Sucher. Chrome-Extension://EFAIDNBMNNNIBPCAJPCGLCLEFINDMKAJ/https://www.nejm.org/doi/pdf/10.1056/nejmoa1905795?articletools=true, April 1, 2007. https://hdl.handle.net/10520/AJA16836707_629.
↑ ^4.0 ^4.1 Herold, Rosanna, Horst Schroten, and Christian Schwerk. 2019. "Virulence Factors of Meningitis-Causing Bacteria: Enabling Brain Entry across the Blood–Brain Barrier" International Journal of Molecular Sciences 20, no. 21: 5393. https://doi.org/10.3390/ijms20215393
↑ Author links open overlay panelKenneth L. Tyler, AbstractThomas Willis (1621–1675) described patients with, R.R. Carpenter, H.D. Chalke, H.V. Smith, J.H. Steele, J. Abercrombie, et al. “Chapter 28 a History of Bacterial Meningitis.” Handbook of Clinical Neurology, November 3, 2009. https://www.sciencedirect.com/science/article/abs/pii/S0072975208021283
↑ Author links open overlay panelKenneth L. Tyler, AbstractThomas Willis (1621–1675) described patients with, R.R. Carpenter, H.D. Chalke, H.V. Smith, J.H. Steele, J. Abercrombie, et al. “Chapter 28 a History of Bacterial Meningitis.” Handbook of Clinical Neurology, November 3, 2009. https://www.sciencedirect.com/science/article/abs/pii/S0072975208021283
↑ ^7.0 ^7.1 “The History of Meningitis.” Meningitis Research Foundation. Accessed April 13, 2024. https://www.meningitis.org/blogs/the-history-of-meningitis#:~:text=Diagnosis%20%26%20Treatment&text=The%20first%20outbreak%20in%20Africa,as%20a%20cause%20of%20meningitis.
↑ VectorMine. “Meninges Vector Illustration. Labeled Anatomical Educational Head...” iStock. Accessed April 14, 2024. https://www.istockphoto.com/vector/meninges-vector-illustration-labeled-anatomy-educational-head-layer-scheme-gm1188270484-335979428.
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↑ “Meningitis. Brain with Normal Meninges and Inflammation of the Meninges. Stock Vector.” Adobe Stock. Accessed April 14, 2024. https://stock.adobe.com/images/meningitis-brain-with-normal-meninges-and-inflammation-of-the-meninges/526052873?asset_id=526052873.
↑ Mehlhorn, Allana, and Brandon Sucher. Chrome-Extension://EFAIDNBMNNNIBPCAJPCGLCLEFINDMKAJ/https://www.nejm.org/doi/pdf/10.1056/nejmoa1905795?articletools=true, April 1, 2007. https://hdl.handle.net/10520/AJA16836707_629.
↑ Mehlhorn, Allana, and Brandon Sucher. Chrome-Extension://EFAIDNBMNNNIBPCAJPCGLCLEFINDMKAJ/https://www.nejm.org/doi/pdf/10.1056/nejmoa1905795?articletools=true, April 1, 2007. https://hdl.handle.net/10520/AJA16836707_629.
↑ Mehlhorn, Allana, and Brandon Sucher. Chrome-Extension://EFAIDNBMNNNIBPCAJPCGLCLEFINDMKAJ/https://www.nejm.org/doi/pdf/10.1056/nejmoa1905795?articletools=true, April 1, 2007. https://hdl.handle.net/10520/AJA16836707_629.
↑ Mehlhorn, Allana, and Brandon Sucher. Chrome-Extension://EFAIDNBMNNNIBPCAJPCGLCLEFINDMKAJ/https://www.nejm.org/doi/pdf/10.1056/nejmoa1905795?articletools=true, April 1, 2007. https://hdl.handle.net/10520/AJA16836707_629.
↑ Library, Kateryna Kon/science Photo. “Causes of Bacterial Meningitis, Illustration - Stock Image - F030/4307.” Science Photo Library. Accessed April 14, 2024. https://www.sciencephoto.com/media/1115984/view/causes-of-bacterial-meningitis-illustration.
↑ ^17.0 ^17.1 ^17.2 ^17.3 ^17.4 “Bacterial Meningitis.” Centers for Disease Control and Prevention, July 15, 2021. https://www.cdc.gov/meningitis/bacterial.html.
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↑ National Research Council (US) Steering Group for the Workshop on Size Limits of Very Small Microorganisms. “Correlates of Smallest Sizes for Microorganisms.” Size Limits of Very Small Microorganisms: Proceedings of a Workshop., January 1, 1999. https://www.ncbi.nlm.nih.gov/books/NBK224751/#:~:text=Escherichia%20coli%20is%20a%20typical,with%20radius%20about%200.5%20micrometers.
↑ Khattak, Zoia E. “Haemophilus Influenzae Infection.” StatPearls [Internet]., April 27, 2023. https://www.ncbi.nlm.nih.gov/books/NBK562176/#:~:text=Haemophilus%20influenzae%20is%20characterized%20as,coccobacillus%20of%20the%20family%20Pasteurellaceae.
↑ Patterson, Maria Jevitz. “Streptococcus.” Medical Microbiology. 4th edition., January 1, 1996. https://www.ncbi.nlm.nih.gov/books/NBK7611/#:~:text=They%20divide%20in%20one%20plane,distinguish%20morphologically%20from%20other%20streptococci.
↑ ^22.0 ^22.1 ^22.2 ^22.3 ^22.4 “Bacterial Meningitis.” Centers for Disease Control and Prevention, July 15, 2021. https://www.cdc.gov/meningitis/bacterial.html.
↑ “Procedure: How to Do a Lumbar Puncture.” EBM Consult. Accessed April 14, 2024. https://www.ebmconsult.com/articles/procedure-lumbar-puncture.
↑ Beek, Diederik van de, Allan Tunkel, Guy Thwaites, and Matthijs Brouwer. Advances in treatment of bacterial meningitis - the lancet, 2012. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)61186-6/fulltext.
↑ ^25.0 ^25.1 YouTube. (2017, November 8). Meningitis - causes, symptoms, diagnosis, treatment, pathology. YouTube. https://www.youtube.com/watch?v=gIHUJs2eTHA
↑ Mehlhorn, Allana, and Brandon Sucher. Chrome Extension://EFAIDNBMNNNIBPCAJPCGLCLEFINDMKAJ/https://www.nejm.org/doi/pdf/10.1056/nejmoa1905795?articletools=true, April 1, 2007. https://hdl.handle.net/10520/AJA16836707_629.
↑ Mehlhorn, Allana, and Brandon Sucher. Chrome-Extension://EFAIDNBMNNNIBPCAJPCGLCLEFINDMKAJ/https://www.nejm.org/doi/pdf/10.1056/nejmoa1905795?articletools=true, April 1, 2007. https://hdl.handle.net/10520/AJA16836707_629.
↑ Mehlhorn, Allana, and Brandon Sucher. Chrome-Extension://EFAIDNBMNNNIBPCAJPCGLCLEFINDMKAJ/https://www.nejm.org/doi/pdf/10.1056/nejmoa1905795?articletools=true, April 1, 2007. https://hdl.handle.net/10520/AJA16836707_629.
↑ ^29.0 ^29.1 Mehlhorn, Allana, and Brandon Sucher. Chrome-Extension://EFAIDNBMNNNIBPCAJPCGLCLEFINDMKAJ/https://www.nejm.org/doi/pdf/10.1056/nejmoa1905795?articletools=true, April 1, 2007. https://hdl.handle.net/10520/AJA16836707_629.
↑ ^30.0 ^30.1 Mehlhorn, Allana, and Brandon Sucher. Chrome-Extension://EFAIDNBMNNNIBPCAJPCGLCLEFINDMKAJ/https://www.nejm.org/doi/pdf/10.1056/nejmoa1905795?articletools=true, April 1, 2007. https://hdl.handle.net/10520/AJA16836707_629.
↑ Hoogman, Martine, Diederik van de Beek, Martijn Weisfelt, Jan de Gans, and Ben Schmand. “Cognitive Outcome in Adults after Bacterial Meningitis.” Journal of Neurology, Neurosurgery & Psychiatry, October 1, 2007. https://jnnp.bmj.com/content/78/10/1092.short.
↑ ^32.0 ^32.1 ^32.2 ^32.3 Hoogman, Martine, Diederik van de Beek, Martijn Weisfelt, Jan de Gans, and Ben Schmand. “Cognitive Outcome in Adults after Bacterial Meningitis.” Journal of Neurology, Neurosurgery & Psychiatry, October 1, 2007. https://jnnp.bmj.com/content/78/10/1092.short.

Authored for BIOL 238 Microbiology, taught by Joan Slonczewski,at Kenyon College,2024

[1] “Bacterial Meningitis: Symptoms, Causes, and Treatment.” Medical News Today. Accessed April 14, 2024. https://www.medicalnewstoday.com/articles/9276#symptoms.

[=ab-2] 2.00 ^2.01 ^2.02 ^2.03 ^2.04 ^2.05 ^2.06 ^2.07 ^2.08 ^2.09 ^2.10 ^2.11 ^2.12 Zainel, Abdulwahed, Hana Mitchell, and Manish Sadarangani. 2021. "Bacterial Meningitis in Children: Neurological Complications, Associated Risk Factors, and Prevention" Microorganisms 9, no. 3: 535. https://doi.org/10.3390/microorganisms9030535

[zz-3] Mehlhorn, Allana, and Brandon Sucher. Chrome-Extension://EFAIDNBMNNNIBPCAJPCGLCLEFINDMKAJ/https://www.nejm.org/doi/pdf/10.1056/nejmoa1905795?articletools=true, April 1, 2007. https://hdl.handle.net/10520/AJA16836707_629.

[=aa-4] 4.0 ^4.1 Herold, Rosanna, Horst Schroten, and Christian Schwerk. 2019. "Virulence Factors of Meningitis-Causing Bacteria: Enabling Brain Entry across the Blood–Brain Barrier" International Journal of Molecular Sciences 20, no. 21: 5393. https://doi.org/10.3390/ijms20215393

[5] Author links open overlay panelKenneth L. Tyler, AbstractThomas Willis (1621–1675) described patients with, R.R. Carpenter, H.D. Chalke, H.V. Smith, J.H. Steele, J. Abercrombie, et al. “Chapter 28 a History of Bacterial Meningitis.” Handbook of Clinical Neurology, November 3, 2009. https://www.sciencedirect.com/science/article/abs/pii/S0072975208021283

[6] Author links open overlay panelKenneth L. Tyler, AbstractThomas Willis (1621–1675) described patients with, R.R. Carpenter, H.D. Chalke, H.V. Smith, J.H. Steele, J. Abercrombie, et al. “Chapter 28 a History of Bacterial Meningitis.” Handbook of Clinical Neurology, November 3, 2009. https://www.sciencedirect.com/science/article/abs/pii/S0072975208021283

[=ee-7] 7.0 ^7.1 “The History of Meningitis.” Meningitis Research Foundation. Accessed April 13, 2024. https://www.meningitis.org/blogs/the-history-of-meningitis#:~:text=Diagnosis%20%26%20Treatment&text=The%20first%20outbreak%20in%20Africa,as%20a%20cause%20of%20meningitis.

[8] VectorMine. “Meninges Vector Illustration. Labeled Anatomical Educational Head...” iStock. Accessed April 14, 2024. https://www.istockphoto.com/vector/meninges-vector-illustration-labeled-anatomy-educational-head-layer-scheme-gm1188270484-335979428.

[tt-9] 9.00 ^9.01 ^9.02 ^9.03 ^9.04 ^9.05 ^9.06 ^9.07 ^9.08 ^9.09 ^9.10 ^9.11 ^9.12 ^9.13 ^9.14 ^9.15 ^9.16 ^9.17 ^9.18 ^9.19 ^9.20 ^9.21 ^9.22 ^9.23 ^9.24 ^9.25 ^9.26 ^9.27 ^9.28 ^9.29 ^9.30 ^9.31 ^9.32 ^9.33 ^9.34 ^9.35 ^9.36 ^9.37 YouTube. (2017, November 8). Meningitis - causes, symptoms, diagnosis, treatment, pathology. YouTube. https://www.youtube.com/watch?v=gIHUJs2eTHA

[aa-10] 10.00 ^10.01 ^10.02 ^10.03 ^10.04 ^10.05 ^10.06 ^10.07 ^10.08 ^10.09 ^10.10 ^10.11 ^10.12 ^10.13 ^10.14 ^10.15 ^10.16 ^10.17 ^10.18 ^10.19 ^10.20 ^10.21 ^10.22 ^10.23 ^10.24 ^10.25 Herold, Rosanna, Horst Schroten, and Christian Schwerk. 2019. "Virulence Factors of Meningitis-Causing Bacteria: Enabling Brain Entry across the Blood–Brain Barrier" International Journal of Molecular Sciences 20, no. 21: 5393. https://doi.org/10.3390/ijms20215393

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[16] Library, Kateryna Kon/science Photo. “Causes of Bacterial Meningitis, Illustration - Stock Image - F030/4307.” Science Photo Library. Accessed April 14, 2024. https://www.sciencephoto.com/media/1115984/view/causes-of-bacterial-meningitis-illustration.

[jj-17] 17.0 ^17.1 ^17.2 ^17.3 ^17.4 “Bacterial Meningitis.” Centers for Disease Control and Prevention, July 15, 2021. https://www.cdc.gov/meningitis/bacterial.html.

[18] Patterson, Maria Jevitz. “Streptococcus.” Medical Microbiology. 4th edition., January 1, 1996. https://www.ncbi.nlm.nih.gov/books/NBK7611/.

[19] National Research Council (US) Steering Group for the Workshop on Size Limits of Very Small Microorganisms. “Correlates of Smallest Sizes for Microorganisms.” Size Limits of Very Small Microorganisms: Proceedings of a Workshop., January 1, 1999. https://www.ncbi.nlm.nih.gov/books/NBK224751/#:~:text=Escherichia%20coli%20is%20a%20typical,with%20radius%20about%200.5%20micrometers.

[20] Khattak, Zoia E. “Haemophilus Influenzae Infection.” StatPearls [Internet]., April 27, 2023. https://www.ncbi.nlm.nih.gov/books/NBK562176/#:~:text=Haemophilus%20influenzae%20is%20characterized%20as,coccobacillus%20of%20the%20family%20Pasteurellaceae.

[21] Patterson, Maria Jevitz. “Streptococcus.” Medical Microbiology. 4th edition., January 1, 1996. https://www.ncbi.nlm.nih.gov/books/NBK7611/#:~:text=They%20divide%20in%20one%20plane,distinguish%20morphologically%20from%20other%20streptococci.

[=jj-22] 22.0 ^22.1 ^22.2 ^22.3 ^22.4 “Bacterial Meningitis.” Centers for Disease Control and Prevention, July 15, 2021. https://www.cdc.gov/meningitis/bacterial.html.

[23] “Procedure: How to Do a Lumbar Puncture.” EBM Consult. Accessed April 14, 2024. https://www.ebmconsult.com/articles/procedure-lumbar-puncture.

[=kk-24] Beek, Diederik van de, Allan Tunkel, Guy Thwaites, and Matthijs Brouwer. Advances in treatment of bacterial meningitis - the lancet, 2012. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)61186-6/fulltext.

[=oo-25] 25.0 ^25.1 YouTube. (2017, November 8). Meningitis - causes, symptoms, diagnosis, treatment, pathology. YouTube. https://www.youtube.com/watch?v=gIHUJs2eTHA

[26] Mehlhorn, Allana, and Brandon Sucher. Chrome Extension://EFAIDNBMNNNIBPCAJPCGLCLEFINDMKAJ/https://www.nejm.org/doi/pdf/10.1056/nejmoa1905795?articletools=true, April 1, 2007. https://hdl.handle.net/10520/AJA16836707_629.

[27] Mehlhorn, Allana, and Brandon Sucher. Chrome-Extension://EFAIDNBMNNNIBPCAJPCGLCLEFINDMKAJ/https://www.nejm.org/doi/pdf/10.1056/nejmoa1905795?articletools=true, April 1, 2007. https://hdl.handle.net/10520/AJA16836707_629.

[28] Mehlhorn, Allana, and Brandon Sucher. Chrome-Extension://EFAIDNBMNNNIBPCAJPCGLCLEFINDMKAJ/https://www.nejm.org/doi/pdf/10.1056/nejmoa1905795?articletools=true, April 1, 2007. https://hdl.handle.net/10520/AJA16836707_629.

[=ss-29] 29.0 ^29.1 Mehlhorn, Allana, and Brandon Sucher. Chrome-Extension://EFAIDNBMNNNIBPCAJPCGLCLEFINDMKAJ/https://www.nejm.org/doi/pdf/10.1056/nejmoa1905795?articletools=true, April 1, 2007. https://hdl.handle.net/10520/AJA16836707_629.

[ss-30] 30.0 ^30.1 Mehlhorn, Allana, and Brandon Sucher. Chrome-Extension://EFAIDNBMNNNIBPCAJPCGLCLEFINDMKAJ/https://www.nejm.org/doi/pdf/10.1056/nejmoa1905795?articletools=true, April 1, 2007. https://hdl.handle.net/10520/AJA16836707_629.

[31] Hoogman, Martine, Diederik van de Beek, Martijn Weisfelt, Jan de Gans, and Ben Schmand. “Cognitive Outcome in Adults after Bacterial Meningitis.” Journal of Neurology, Neurosurgery & Psychiatry, October 1, 2007. https://jnnp.bmj.com/content/78/10/1092.short.

[qq-32] 32.0 ^32.1 ^32.2 ^32.3 Hoogman, Martine, Diederik van de Beek, Martijn Weisfelt, Jan de Gans, and Ben Schmand. “Cognitive Outcome in Adults after Bacterial Meningitis.” Journal of Neurology, Neurosurgery & Psychiatry, October 1, 2007. https://jnnp.bmj.com/content/78/10/1092.short.

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 ====Virulence Factors====
-Virulence factors that are used by gram-positive and gram-negative bacteria include adhesions and internalins, pore-forming toxins, and factors that promote intracellular movement and cell-to-cell spread<ref name=aa>Herold, Rosanna, Horst Schroten, and Christian Schwerk. 2019. "Virulence Factors of Meningitis-Causing Bacteria: Enabling Brain Entry across the Blood–Brain Barrier" International Journal of Molecular Sciences 20, no. 21: 5393. https://doi.org/10.3390/ijms20215393</ref>. Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae all produce a polysaccharide capsule that helps them invade the host without any damage and resist phagocytosis<ref name=aa>Herold, Rosanna, Horst Schroten, and Christian Schwerk. 2019. "Virulence Factors of Meningitis-Causing Bacteria: Enabling Brain Entry across the Blood–Brain Barrier" International Journal of Molecular Sciences 20, no. 21: 5393. https://doi.org/10.3390/ijms20215393</ref>. Surface proteins like adhesions allow the pathogen to attach to the host cells and endotoxins are possessed by gram-negative bacteria like N. meningitidis, E.coli, S. pneumonia, and H. Inflenzae which induces inflammation and tissue damage<ref name=aa>Herold, Rosanna, Horst Schroten, and Christian Schwerk. 2019. "Virulence Factors of Meningitis-Causing Bacteria: Enabling Brain Entry across the Blood–Brain Barrier" International Journal of Molecular Sciences 20, no. 21: 5393. https://doi.org/10.3390/ijms20215393</ref>.
+Virulence factors that are used by gram-positive and gram-negative bacteria include adhesions and internalins, pore-forming toxins, and factors that promote intracellular movement and cell-to-cell spread<ref name=aa>Herold, Rosanna, Horst Schroten, and Christian Schwerk. 2019. "Virulence Factors of Meningitis-Causing Bacteria: Enabling Brain Entry across the Blood–Brain Barrier" International Journal of Molecular Sciences 20, no. 21: 5393. https://doi.org/10.3390/ijms20215393</ref>. <i>Streptococcus pneumonia</i>, <i>Neisseria meningitidis</i>, and <i>Haemophilus influenza</i> all produce a polysaccharide capsule that helps them invade the host without any damage and resist phagocytosis<ref name=aa>Herold, Rosanna, Horst Schroten, and Christian Schwerk. 2019. "Virulence Factors of Meningitis-Causing Bacteria: Enabling Brain Entry across the Blood–Brain Barrier" International Journal of Molecular Sciences 20, no. 21: 5393. https://doi.org/10.3390/ijms20215393</ref>. Surface proteins like adhesions allow the pathogen to attach to the host cells and endotoxins are possessed by gram-negative bacteria like <i>N. meningitidis</i>, <i>E.coli</i>, <i>S. pneumonia</i>, and <i>H. Inflenzae</i> which induces inflammation and tissue damage<ref name=aa>Herold, Rosanna, Horst Schroten, and Christian Schwerk. 2019. "Virulence Factors of Meningitis-Causing Bacteria: Enabling Brain Entry across the Blood–Brain Barrier" International Journal of Molecular Sciences 20, no. 21: 5393. https://doi.org/10.3390/ijms20215393</ref>.
 ====What Triggers Inflammation?====
@@ Line 38: / Line 37: @@
 [[File:1000 F 526052873 t4gWHCRTR3vOE1UPwumyx9LDJZbMfJs1.jpg|thumb|300px|left|Graphic showing a brain with normal meninges compared to a brain with inflamed meninges.<ref>“Meningitis. Brain with Normal Meninges and Inflammation of the Meninges. Stock Vector.” Adobe Stock. Accessed April 14, 2024. https://stock.adobe.com/images/meningitis-brain-with-normal-meninges-and-inflammation-of-the-meninges/526052873?asset_id=526052873.</ref> Photo credit [https://stock.adobe.com/images/meningitis-brain-with-normal-meninges-and-inflammation-of-the-meninges/526052873?asset_id=526052873]]]
-It can be caused by an autoimmune disease, where the body attacks itself or the body could experience an unfavorable reaction to a certain medication<ref name=tt>YouTube. (2017, November 8). Meningitis - causes, symptoms, diagnosis, treatment, pathology. YouTube. https://www.youtube.com/watch?v=gIHUJs2eTHA</ref>. This can occur during intrathecal therapy (medication is injected directly into the CSF)<ref name=tt>YouTube. (2017, November 8). Meningitis - causes, symptoms, diagnosis, treatment, pathology. YouTube. https://www.youtube.com/watch?v=gIHUJs2eTHA</ref>. The most common way of contracting the disease is by infection across all ages (ex. Neisseria meningitidis bacteria or herpes simplex virus)<ref name=tt>YouTube. (2017, November 8). Meningitis - causes, symptoms, diagnosis, treatment, pathology. YouTube. https://www.youtube.com/watch?v=gIHUJs2eTHA</ref>. There are two routes the infection can take to reach the leptomeninges and the CSF. The first route is direct spread, which is when the pathogen gets inside the spinal column or skin and then penetrates the meninges, leading into the CSF<ref name=tt>YouTube. (2017, November 8). Meningitis - causes, symptoms, diagnosis, treatment, pathology. YouTube. https://www.youtube.com/watch?v=gIHUJs2eTHA</ref>. The pathogen will either come through the skin or up the nose<ref name=tt>YouTube. (2017, November 8). Meningitis - causes, symptoms, diagnosis, treatment, pathology. YouTube. https://www.youtube.com/watch?v=gIHUJs2eTHA</ref>. The second route is through hematogenous spread, which is when the pathogen enters the bloodstream and moves through the endothelial cells in the blood vessels making up the blood-brain barrier and entering the CSF<ref name=tt>YouTube. (2017, November 8). Meningitis - causes, symptoms, diagnosis, treatment, pathology. YouTube. https://www.youtube.com/watch?v=gIHUJs2eTHA</ref>. Bacteria will do this by binding to surface receptors on the endothelial cells to get across the barrier<ref name=tt>YouTube. (2017, November 8). Meningitis - causes, symptoms, diagnosis, treatment, pathology. YouTube. https://www.youtube.com/watch?v=gIHUJs2eTHA</ref>. If not, they will find other areas to damage like the choroid plexus<ref name=tt>YouTube. (2017, November 8). Meningitis - causes, symptoms, diagnosis, treatment, pathology. YouTube. https://www.youtube.com/watch?v=gIHUJs2eTHA</ref>. Once it enters the CSF, it can start replicating and spreading. The white cells will eventually detect the pathogenic cells and send cytokines to bring in more immune cells<ref name=tt>YouTube. (2017, November 8). Meningitis - causes, symptoms, diagnosis, treatment, pathology. YouTube. https://www.youtube.com/watch?v=gIHUJs2eTHA</ref>. Over time, the concentration of white blood cells in a microliter of cerebrospinal fluid (CSF)can increase to thousands<ref name=tt>YouTube. (2017, November 8). Meningitis - causes, symptoms, diagnosis, treatment, pathology. YouTube. https://www.youtube.com/watch?v=gIHUJs2eTHA</ref>. However, exceeding five cells typically indicates meningitis<ref name=tt>YouTube. (2017, November 8). Meningitis - causes, symptoms, diagnosis, treatment, pathology. YouTube. https://www.youtube.com/watch?v=gIHUJs2eTHA</ref>. In bacterial infections, the count usually surpasses 100 cells per microliter, with more than 90% being polymorphonuclear leukocytes (PMNs)<ref name=tt>YouTube. (2017, November 8). Meningitis - causes, symptoms, diagnosis, treatment, pathology. YouTube. https://www.youtube.com/watch?v=gIHUJs2eTHA</ref>. Viral meningitis is usually present with 10-100 white blood cells per microliter (consisting of over 50% lymphocytes and fever than 20% PMNs)<ref name=tt>YouTube. (2017, November 8). Meningitis - causes, symptoms, diagnosis, treatment, pathology. YouTube. https://www.youtube.com/watch?v=gIHUJs2eTHA</ref>. Fungal meningitis typically exhibits 10-500 white blood cells with lymphocytes accounting for over 50%<ref name=tt>YouTube. (2017, November 8). Meningitis - causes, symptoms, diagnosis, treatment, pathology. YouTube. https://www.youtube.com/watch?v=gIHUJs2eTHA</ref>. In tuberculous meningitis, white blood cell count ranges from 50-500 cells per microliter (lymphocytes constituting over 80%). The pressure from the additional immune cells will most likely rise above 200 nm of water<ref name=tt>YouTube. (2017, November 8). Meningitis - causes, symptoms, diagnosis, treatment, pathology. YouTube. https://www.youtube.com/watch?v=gIHUJs2eTHA</ref>. The immune system will also induce the glucose concentration to drop in the CSF, up to below 2 ⁄ 3 of the concentration in the blood, making the protein levels increase to over 50 mg/dL<ref name=tt>YouTube. (2017, November 8). Meningitis - causes, symptoms, diagnosis, treatment, pathology. YouTube. https://www.youtube.com/watch?v=gIHUJs2eTHA</ref>
+It can be caused by an autoimmune disease, where the body attacks itself or the body could experience an unfavorable reaction to a certain medication<ref name=tt>YouTube. (2017, November 8). Meningitis - causes, symptoms, diagnosis, treatment, pathology. YouTube. https://www.youtube.com/watch?v=gIHUJs2eTHA</ref>. This can occur during intrathecal therapy (medication is injected directly into the CSF)<ref name=tt>YouTube. (2017, November 8). Meningitis - causes, symptoms, diagnosis, treatment, pathology. YouTube. https://www.youtube.com/watch?v=gIHUJs2eTHA</ref>. The most common way of contracting the disease is by infection across all ages (ex. <i>Neisseria meningitidis</i> bacteria or herpes simplex virus)<ref name=tt>YouTube. (2017, November 8). Meningitis - causes, symptoms, diagnosis, treatment, pathology. YouTube. https://www.youtube.com/watch?v=gIHUJs2eTHA</ref>. There are two routes the infection can take to reach the leptomeninges and the CSF. The first route is direct spread, which is when the pathogen gets inside the spinal column or skin and then penetrates the meninges, leading into the CSF<ref name=tt>YouTube. (2017, November 8). Meningitis - causes, symptoms, diagnosis, treatment, pathology. YouTube. https://www.youtube.com/watch?v=gIHUJs2eTHA</ref>. The pathogen will either come through the skin or up the nose<ref name=tt>YouTube. (2017, November 8). Meningitis - causes, symptoms, diagnosis, treatment, pathology. YouTube. https://www.youtube.com/watch?v=gIHUJs2eTHA</ref>. The second route is through hematogenous spread, which is when the pathogen enters the bloodstream and moves through the endothelial cells in the blood vessels making up the blood-brain barrier and entering the CSF<ref name=tt>YouTube. (2017, November 8). Meningitis - causes, symptoms, diagnosis, treatment, pathology. YouTube. https://www.youtube.com/watch?v=gIHUJs2eTHA</ref>. Bacteria will do this by binding to surface receptors on the endothelial cells to get across the barrier<ref name=tt>YouTube. (2017, November 8). Meningitis - causes, symptoms, diagnosis, treatment, pathology. YouTube. https://www.youtube.com/watch?v=gIHUJs2eTHA</ref>. If not, they will find other areas to damage like the choroid plexus<ref name=tt>YouTube. (2017, November 8). Meningitis - causes, symptoms, diagnosis, treatment, pathology. YouTube. https://www.youtube.com/watch?v=gIHUJs2eTHA</ref>. Once it enters the CSF, it can start replicating and spreading. The white cells will eventually detect the pathogenic cells and send cytokines to bring in more immune cells<ref name=tt>YouTube. (2017, November 8). Meningitis - causes, symptoms, diagnosis, treatment, pathology. YouTube. https://www.youtube.com/watch?v=gIHUJs2eTHA</ref>. Over time, the concentration of white blood cells in a microliter of cerebrospinal fluid (CSF)can increase to thousands<ref name=tt>YouTube. (2017, November 8). Meningitis - causes, symptoms, diagnosis, treatment, pathology. YouTube. https://www.youtube.com/watch?v=gIHUJs2eTHA</ref>. However, exceeding five cells typically indicates meningitis<ref name=tt>YouTube. (2017, November 8). Meningitis - causes, symptoms, diagnosis, treatment, pathology. YouTube. https://www.youtube.com/watch?v=gIHUJs2eTHA</ref>. In bacterial infections, the count usually surpasses 100 cells per microliter, with more than 90% being polymorphonuclear leukocytes (PMNs)<ref name=tt>YouTube. (2017, November 8). Meningitis - causes, symptoms, diagnosis, treatment, pathology. YouTube. https://www.youtube.com/watch?v=gIHUJs2eTHA</ref>. Viral meningitis is usually present with 10-100 white blood cells per microliter (consisting of over 50% lymphocytes and fever than 20% PMNs)<ref name=tt>YouTube. (2017, November 8). Meningitis - causes, symptoms, diagnosis, treatment, pathology. YouTube. https://www.youtube.com/watch?v=gIHUJs2eTHA</ref>. Fungal meningitis typically exhibits 10-500 white blood cells with lymphocytes accounting for over 50%<ref name=tt>YouTube. (2017, November 8). Meningitis - causes, symptoms, diagnosis, treatment, pathology. YouTube. https://www.youtube.com/watch?v=gIHUJs2eTHA</ref>. In tuberculous meningitis, white blood cell count ranges from 50-500 cells per microliter (lymphocytes constituting over 80%). The pressure from the additional immune cells will most likely rise above 200 nm of water<ref name=tt>YouTube. (2017, November 8). Meningitis - causes, symptoms, diagnosis, treatment, pathology. YouTube. https://www.youtube.com/watch?v=gIHUJs2eTHA</ref>. The immune system will also induce the glucose concentration to drop in the CSF, up to below 2 ⁄ 3 of the concentration in the blood, making the protein levels increase to over 50 mg/dL<ref name=tt>YouTube. (2017, November 8). Meningitis - causes, symptoms, diagnosis, treatment, pathology. YouTube. https://www.youtube.com/watch?v=gIHUJs2eTHA</ref>
 .
 ===Causes and Risk Factors===
 ====Age====
-Everyone is susceptible to catching bacteria meningitis. However, multiple pathogens infect certain age groups more than others. Infants are most likely infected by Group B streptococcus (ex. <i>Streptococcus agalactiae</i>), gram-negative enteric organisms (ex. E.coli), and <i>Listeria monocytogenes</i> (<i>L. monocytogenes</i>)<ref>Mehlhorn, Allana, and Brandon Sucher. Chrome-Extension://EFAIDNBMNNNIBPCAJPCGLCLEFINDMKAJ/https://www.nejm.org/doi/pdf/10.1056/nejmoa1905795?articletools=true, April 1, 2007. https://hdl.handle.net/10520/AJA16836707_629.</ref>. 1 to 23 month olds are susceptible to <i>Streptococcus pneumonia</i> (<i>S. pneumonia</i>), <i>Neisseria meningitidis</i> (<i>N. meningitides</i>), <i>S. agalactiae, Haemophilus influenzae (H. influenza)</i>, and E.coli<ref>Mehlhorn, Allana, and Brandon Sucher. Chrome-Extension://EFAIDNBMNNNIBPCAJPCGLCLEFINDMKAJ/https://www.nejm.org/doi/pdf/10.1056/nejmoa1905795?articletools=true, April 1, 2007. https://hdl.handle.net/10520/AJA16836707_629.</ref>. Children and teens are most likely infected with N. meningitidis and S. pneumoniae <ref name=tt>YouTube. (2017, November 8). Meningitis - causes, symptoms, diagnosis, treatment, pathology. YouTube. https://www.youtube.com/watch?v=gIHUJs2eTHA</ref>. Those who are adults and elderly will most likely contract S. pneumoniae, and L. monocytogenes <ref name=tt>YouTube. (2017, November 8). Meningitis - causes, symptoms, diagnosis, treatment, pathology. YouTube. https://www.youtube.com/watch?v=gIHUJs2eTHA</ref>. If you are over 50 years of age, N. meningitidis is also likely as well<ref>Mehlhorn, Allana, and Brandon Sucher. Chrome-Extension://EFAIDNBMNNNIBPCAJPCGLCLEFINDMKAJ/https://www.nejm.org/doi/pdf/10.1056/nejmoa1905795?articletools=true, April 1, 2007. https://hdl.handle.net/10520/AJA16836707_629.</ref>.The immunocompromised status of the infected patient is also an important factor to consider for the rate of survival<ref>Mehlhorn, Allana, and Brandon Sucher. Chrome-Extension://EFAIDNBMNNNIBPCAJPCGLCLEFINDMKAJ/https://www.nejm.org/doi/pdf/10.1056/nejmoa1905795?articletools=true, April 1, 2007. https://hdl.handle.net/10520/AJA16836707_629.</ref>.
+Everyone is susceptible to catching bacteria meningitis. However, multiple pathogens infect certain age groups more than others. Infants are most likely infected by Group B streptococcus (ex. <i>Streptococcus agalactiae</i>), gram-negative enteric organisms (ex. <i>E.coli</i>), and <i>Listeria monocytogenes</i> (<i>L. monocytogenes</i>)<ref>Mehlhorn, Allana, and Brandon Sucher. Chrome-Extension://EFAIDNBMNNNIBPCAJPCGLCLEFINDMKAJ/https://www.nejm.org/doi/pdf/10.1056/nejmoa1905795?articletools=true, April 1, 2007. https://hdl.handle.net/10520/AJA16836707_629.</ref>. 1 to 23 month olds are susceptible to <i>Streptococcus pneumonia</i> (<i>S. pneumonia</i>), <i>Neisseria meningitidis</i> (<i>N. meningitides</i>), <i>S. agalactiae, Haemophilus influenzae (H. influenza)</i>, and <i>E.coli</i><ref>Mehlhorn, Allana, and Brandon Sucher. Chrome-Extension://EFAIDNBMNNNIBPCAJPCGLCLEFINDMKAJ/https://www.nejm.org/doi/pdf/10.1056/nejmoa1905795?articletools=true, April 1, 2007. https://hdl.handle.net/10520/AJA16836707_629.</ref>. Children and teens are most likely infected with <i>N. meningitidis</i> and <i>S. pneumonia</i> <ref name=tt>YouTube. (2017, November 8). Meningitis - causes, symptoms, diagnosis, treatment, pathology. YouTube. https://www.youtube.com/watch?v=gIHUJs2eTHA</ref>. Those who are adults and elderly will most likely contract <i>S. pneumonia</i>, and <i>L. monocytogenes</i> <ref name=tt>YouTube. (2017, November 8). Meningitis - causes, symptoms, diagnosis, treatment, pathology. YouTube. https://www.youtube.com/watch?v=gIHUJs2eTHA</ref>. If you are over 50 years of age, <i>N. meningitidis</i> is also likely as well<ref>Mehlhorn, Allana, and Brandon Sucher. Chrome-Extension://EFAIDNBMNNNIBPCAJPCGLCLEFINDMKAJ/https://www.nejm.org/doi/pdf/10.1056/nejmoa1905795?articletools=true, April 1, 2007. https://hdl.handle.net/10520/AJA16836707_629.</ref>.The immunocompromised status of the infected patient is also an important factor to consider for the rate of survival<ref>Mehlhorn, Allana, and Brandon Sucher. Chrome-Extension://EFAIDNBMNNNIBPCAJPCGLCLEFINDMKAJ/https://www.nejm.org/doi/pdf/10.1056/nejmoa1905795?articletools=true, April 1, 2007. https://hdl.handle.net/10520/AJA16836707_629.</ref>.
 ====Bacterial Families====
 [[File:F0304307-800px-wm.jpg|thumb|380px|right|Magnified images of different bacteria that cause meningitis.<ref>Library, Kateryna Kon/science Photo. “Causes of Bacterial Meningitis, Illustration - Stock Image - F030/4307.” Science Photo Library. Accessed April 14, 2024. https://www.sciencephoto.com/media/1115984/view/causes-of-bacterial-meningitis-illustration. </ref> Photo credit [https://www.sciencephoto.com/media/1115984/view/causes-of-bacterial-meningitis-illustration]]]
-As previously mentioned, multiple bacteria can cause bacterial meningitis. Some examples are Group B Streptococcus, E.coli,<i> H. Influenza</i>, <i>M. tuberculosis</i>, <i>S. pneumonia</i>, and <i>N. meningitidis</i> <ref name=jj>“Bacterial Meningitis.” Centers for Disease Control and Prevention, July 15, 2021. https://www.cdc.gov/meningitis/bacterial.html.</ref>. Group B Streptococcus measures between 0.5-1.25 micrometers <ref>Patterson, Maria Jevitz. “Streptococcus.” Medical Microbiology. 4th edition., January 1, 1996. https://www.ncbi.nlm.nih.gov/books/NBK7611/.</ref>, E.coli measures between 1.0-2.0 micrometers long <ref>National Research Council (US) Steering Group for the Workshop on Size Limits of Very Small Microorganisms. “Correlates of Smallest Sizes for Microorganisms.” Size Limits of Very Small Microorganisms: Proceedings of a Workshop., January 1, 1999. https://www.ncbi.nlm.nih.gov/books/NBK224751/#:~:text=Escherichia%20coli%20is%20a%20typical,with%20radius%20about%200.5%20micrometers.</ref>, <i>H.influenzae</i> measures between 0.3-1 mircrometers <ref>Khattak, Zoia E. “Haemophilus Influenzae Infection.” StatPearls [Internet]., April 27, 2023. https://www.ncbi.nlm.nih.gov/books/NBK562176/#:~:text=Haemophilus%20influenzae%20is%20characterized%20as,coccobacillus%20of%20the%20family%20Pasteurellaceae.</ref>, <i>S. pneumonaie</i> measures between 0.5-1.25 micrometers long<ref>Patterson, Maria Jevitz. “Streptococcus.” Medical Microbiology. 4th edition., January 1, 1996. https://www.ncbi.nlm.nih.gov/books/NBK7611/#:~:text=They%20divide%20in%20one%20plane,distinguish%20morphologically%20from%20other%20streptococci.</ref>. Bacterial meningitis can spread through various ways, depending on the bacteria causing the infection. Some individuals will not experience symptoms, but will still be "carriers" of that bacteria that can still be spread to those around them<ref name==jj>“Bacterial Meningitis.” Centers for Disease Control and Prevention, July 15, 2021. https://www.cdc.gov/meningitis/bacterial.html.</ref>. For instance, Group B Streptococcus and E.coli are usually passed from the mothers to newborns during childbirth<ref name==jj>“Bacterial Meningitis.” Centers for Disease Control and Prevention, July 15, 2021. https://www.cdc.gov/meningitis/bacterial.html.</ref>. <i>H. influenza, M. tuberculosis</i>, and <i> S. pneumonia</i> are typically transmitted through respiratory droplets through coughing and sneezing during close contact interactions<ref name==jj>“Bacterial Meningitis.” Centers for Disease Control and Prevention, July 15, 2021. https://www.cdc.gov/meningitis/bacterial.html.</ref>. <i>N. meningitidis</i>, however, spreads through the sharing of respiratory or throat secretions such as saliva or split, which occurs through living in the same proximity, kissing, and coughing<ref name==jj>“Bacterial Meningitis.” Centers for Disease Control and Prevention, July 15, 2021. https://www.cdc.gov/meningitis/bacterial.html.</ref>. E.coli can be transmitted through food consumption or by the preparation of the food<ref name==jj>“Bacterial Meningitis.” Centers for Disease Control and Prevention, July 15, 2021. https://www.cdc.gov/meningitis/bacterial.html.</ref>
+As previously mentioned, multiple bacteria can cause bacterial meningitis. Some examples are Group B Streptococcus, <i>E.coli</i>,<i> H. Influenza</i>, <i>M. tuberculosis</i>, <i>S. pneumonia</i>, and <i>N. meningitidis</i> <ref name=jj>“Bacterial Meningitis.” Centers for Disease Control and Prevention, July 15, 2021. https://www.cdc.gov/meningitis/bacterial.html.</ref>. Group B Streptococcus measures between 0.5-1.25 micrometers <ref>Patterson, Maria Jevitz. “Streptococcus.” Medical Microbiology. 4th edition., January 1, 1996. https://www.ncbi.nlm.nih.gov/books/NBK7611/.</ref>, <i>E.coli</i> measures between 1.0-2.0 micrometers long <ref>National Research Council (US) Steering Group for the Workshop on Size Limits of Very Small Microorganisms. “Correlates of Smallest Sizes for Microorganisms.” Size Limits of Very Small Microorganisms: Proceedings of a Workshop., January 1, 1999. https://www.ncbi.nlm.nih.gov/books/NBK224751/#:~:text=Escherichia%20coli%20is%20a%20typical,with%20radius%20about%200.5%20micrometers.</ref>, <i>H.influenzae</i> measures between 0.3-1 mircrometers <ref>Khattak, Zoia E. “Haemophilus Influenzae Infection.” StatPearls [Internet]., April 27, 2023. https://www.ncbi.nlm.nih.gov/books/NBK562176/#:~:text=Haemophilus%20influenzae%20is%20characterized%20as,coccobacillus%20of%20the%20family%20Pasteurellaceae.</ref>, <i>S. pneumonaie</i> measures between 0.5-1.25 micrometers long<ref>Patterson, Maria Jevitz. “Streptococcus.” Medical Microbiology. 4th edition., January 1, 1996. https://www.ncbi.nlm.nih.gov/books/NBK7611/#:~:text=They%20divide%20in%20one%20plane,distinguish%20morphologically%20from%20other%20streptococci.</ref>. Bacterial meningitis can spread through various ways, depending on the bacteria causing the infection. Some individuals will not experience symptoms, but will still be "carriers" of that bacteria that can still be spread to those around them<ref name==jj>“Bacterial Meningitis.” Centers for Disease Control and Prevention, July 15, 2021. https://www.cdc.gov/meningitis/bacterial.html.</ref>. For instance, Group B Streptococcus and <i>E.coli</i> are usually passed from the mothers to newborns during childbirth<ref name==jj>“Bacterial Meningitis.” Centers for Disease Control and Prevention, July 15, 2021. https://www.cdc.gov/meningitis/bacterial.html.</ref>. <i>H. influenza, M. tuberculosis</i>, and <i> S. pneumonia</i> are typically transmitted through respiratory droplets through coughing and sneezing during close contact interactions<ref name==jj>“Bacterial Meningitis.” Centers for Disease Control and Prevention, July 15, 2021. https://www.cdc.gov/meningitis/bacterial.html.</ref>. <i>N. meningitidis</i>, however, spreads through the sharing of respiratory or throat secretions such as saliva or split, which occurs through living in the same proximity, kissing, and coughing<ref name==jj>“Bacterial Meningitis.” Centers for Disease Control and Prevention, July 15, 2021. https://www.cdc.gov/meningitis/bacterial.html.</ref>. <i>E.coli</i> can be transmitted through food consumption or by the preparation of the food<ref name==jj>“Bacterial Meningitis.” Centers for Disease Control and Prevention, July 15, 2021. https://www.cdc.gov/meningitis/bacterial.html.</ref>
 ==Symptoms and Diagnosis==
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 ==Conclusion==
-Bacterial meningitis remains a formidable challenge in healthcare and it is one of the oldest known infections of mankind. The causative agents, including <i>S. pneumonia, H.influenzae, and M. meningitidis</i> have distinct characteristics and transmission routes contributing to the complexity of the disease. Understanding the pathophysiology of bacterial meningitis and the intricate mechanisms of invasion helps advance the treatment for these infections. Diagnosis and treatment strategies have evolved, emphasizing recognition, antibiotic therapy, and supportive care. Vaccination is crucial for prevention, as it targets the most common microbial etiologies of bacterial meningitis. However, challenges are still prevalent, including antibiotic resistance, variability in clinical presentation, and the impact of neurological complications on patients. Further research and public health efforts are important for fighting against the pathogens that cause meningitis and improving the outcome of patients.
+Bacterial meningitis remains a formidable challenge in healthcare and it is one of the oldest known infections of mankind. The causative agents, including <i>S. pneumonia, H.influenzae, and N. meningitidis</i> have distinct characteristics and transmission routes contributing to the complexity of the disease. Understanding the pathophysiology of bacterial meningitis and the intricate mechanisms of invasion helps advance the treatment for these infections. Diagnosis and treatment strategies have evolved, emphasizing recognition, antibiotic therapy, and supportive care. Vaccination is crucial for prevention, as it targets the most common microbial etiologies of bacterial meningitis. However, challenges are still prevalent, including antibiotic resistance, variability in clinical presentation, and the impact of neurological complications on patients. Further research and public health efforts are important for fighting against the pathogens that cause meningitis and improving the outcome of patients.
 ==References==
 <references />
 <br><br>Authored for BIOL 238 Microbiology, taught by [https://biology.kenyon.edu/slonc/slonc.htm Joan Slonczewski,]at [http://www.kenyon.edu/index.xml Kenyon College,]2024