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''Neisseria meningitidis'', often referred to as meningococcus, is a
Gram-negative bacterium Gram-negative bacteria are bacteria that do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. They are characterized by their cell envelopes, which are composed of a thin peptidoglycan cell wall ...
that can cause
meningitis Meningitis is acute or chronic inflammation of the protective membranes covering the brain and spinal cord, collectively called the meninges. The most common symptoms are fever, headache, and neck stiffness. Other symptoms include confusion or ...
and other forms of
meningococcal disease Meningococcal disease describes infections caused by the bacterium ''Neisseria meningitidis'' (also termed meningococcus). It has a high mortality rate if untreated but is vaccine-preventable. While best known as a cause of meningitis, it can al ...
such as
meningococcemia Meningococcal disease describes infections caused by the bacterium ''Neisseria meningitidis'' (also termed meningococcus). It has a high mortality rate if untreated but is vaccine-preventable. While best known as a cause of meningitis, it can al ...
, a life-threatening
sepsis Sepsis, formerly known as septicemia (septicaemia in British English) or blood poisoning, is a life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage is follo ...
. The bacterium is referred to as a
coccus A coccus (plural cocci) is any bacterium or archaeon that has a spherical, ovoid, or generally round shape. Bacteria are categorized based on their shapes into three classes: cocci (spherical-shaped), bacillus (rod-shaped) and spiral ( of whi ...
because it is round, and more specifically a diplococcus because of its tendency to form pairs. About 10% of adults are carriers of the bacteria in their
nasopharynx The pharynx (plural: pharynges) is the part of the throat behind the mouth and nasal cavity, and above the oesophagus and trachea (the tubes going down to the stomach and the lungs). It is found in vertebrates and invertebrates, though its struct ...
. As an exclusively human pathogen, it is the main cause of
bacterial meningitis Meningitis is acute or chronic inflammation of the protective membranes covering the brain and spinal cord, collectively called the meninges. The most common symptoms are fever, headache, and neck stiffness. Other symptoms include confusi ...
in children and young adults, causing developmental impairment and death in about 10% of cases. It causes the only form of bacterial meningitis known to occur
epidemic An epidemic (from Greek ἐπί ''epi'' "upon or above" and δῆμος ''demos'' "people") is the rapid spread of disease to a large number of patients among a given population within an area in a short period of time. Epidemics of infectious ...
ally, mainly in Africa and Asia. It occurs worldwide in both epidemic and endemic form. ''N. meningitidis'' is spread through saliva and respiratory secretions during coughing, sneezing, kissing, chewing on toys and through sharing a source of fresh water. It has also been reported to be transmitted through oral sex and cause
urethritis Urethritis is the inflammation of the urethra. The most common symptoms include painful or difficult urination and urethral discharge. It is a commonly treatable condition usually caused by infection with bacteria. This bacterial infection is oft ...
in men. It infects its host cells by sticking to them with long thin extensions called
pili Pili may refer to: Common names of plants * '' Canarium ovatum'', a Philippine tree that is a source of the pili nut * ''Heteropogon contortus'', a Hawaiian grass used to thatch structures Places * Pili, Camarines Sur, is a municipality in the ...
and the surface-exposed proteins Opa and Opc and has several virulence factors.


Signs and symptoms

Meningococcus can cause
meningitis Meningitis is acute or chronic inflammation of the protective membranes covering the brain and spinal cord, collectively called the meninges. The most common symptoms are fever, headache, and neck stiffness. Other symptoms include confusion or ...
and other forms of meningococcal disease. It initially produces general symptoms like
fatigue Fatigue describes a state of tiredness that does not resolve with rest or sleep. In general usage, fatigue is synonymous with extreme tiredness or exhaustion that normally follows prolonged physical or mental activity. When it does not resolve ...
, fever, and headache and can rapidly progress to
neck stiffness Neck stiffness, stiff neck and nuchal rigidity are terms often used interchangeably to describe the medical condition when one experiences discomfort or pain when trying to turn, move, or flex the neck. Possible causes include muscle strain or spr ...
, coma and death in 10% of cases.
Petechia A petechia () is a small red or purple spot (≤4 mm in diameter) that can appear on the skin, conjunctiva, retina, and mucous membranes which is caused by haemorrhage of capillaries. The word is derived from Italian , 'freckle,' of obscure origi ...
e occur in about 50% of cases. Chance of survival is highly correlated with blood cortisol levels, with lower levels prior to steroid administration corresponding with increased patient mortality. Symptoms of meningococcal meningitis are easily confused with those caused by other bacteria, such as ''
Haemophilus influenzae ''Haemophilus influenzae'' (formerly called Pfeiffer's bacillus or ''Bacillus influenzae'') is a Gram-negative, non-motile, coccobacillary, facultatively anaerobic, capnophilic pathogenic bacterium of the family Pasteurellaceae. The bact ...
'' and ''
Streptococcus pneumoniae ''Streptococcus pneumoniae'', or pneumococcus, is a Gram-positive, spherical bacteria, alpha-hemolytic (under aerobic conditions) or beta-hemolytic (under anaerobic conditions), aerotolerant anaerobic member of the genus Streptococcus. They ar ...
''. Suspicion of meningitis is a
medical emergency A medical emergency is an acute injury or illness that poses an immediate risk to a person's life or long-term health, sometimes referred to as a situation risking "life or limb". These emergencies may require assistance from another, qualified ...
and immediate medical assessment is recommended. Current guidance in the United Kingdom is that if a case of meningococcal meningitis or
septicaemia Sepsis, formerly known as septicemia (septicaemia in British English) or blood poisoning, is a life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage is follo ...
(infection of the blood) is suspected, intravenous antibiotics should be given and the ill person admitted to the hospital. This means that laboratory tests may be less likely to confirm the presence of ''Neisseria meningitidis'' as the antibiotics will dramatically lower the number of bacteria in the body. The UK guidance is based on the idea that the reduced ability to identify the bacteria is outweighed by reduced chance of death.
Septicaemia Sepsis, formerly known as septicemia (septicaemia in British English) or blood poisoning, is a life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage is follo ...
caused by ''Neisseria meningitidis'' has received much less public attention than meningococcal meningitis even though septicaemia has been linked to infant deaths. Meningococcal septicaemia typically causes a
purpuric Purpura () is a condition of red or purple discolored spots on the skin that do not blanch on applying pressure. The spots are caused by bleeding underneath the skin secondary to platelet disorders, vascular disorders, coagulation disorders, ...
rash, that does not lose its color when pressed with a glass slide (" non-blanching") and does not cause the classical symptoms of meningitis. This means the condition may be ignored by those not aware of the significance of the rash. Septicaemia carries an approximate 50%
mortality rate Mortality rate, or death rate, is a measure of the number of deaths (in general, or due to a specific cause) in a particular population, scaled to the size of that population, per unit of time. Mortality rate is typically expressed in units of d ...
over a few hours from initial onset. Other severe complications include Waterhouse–Friderichsen syndrome, a massive, usually bilateral, hemorrhage into the adrenal glands caused by
fulminant Fulminant () is a medical descriptor for any event or process that occurs suddenly and escalates quickly, and is intense and severe to the point of lethality, i.e., it has an explosive character. The word comes from Latin ''fulmināre'', to stri ...
meningococcemia,
adrenal insufficiency Adrenal insufficiency is a condition in which the adrenal glands do not produce adequate amounts of steroid hormones. The adrenal gland normally secretes glucocorticoids (primarily cortisol), mineralocorticoids (primarily aldosterone), and andro ...
, and
disseminated intravascular coagulation Disseminated intravascular coagulation (DIC) is a condition in which blood clots form throughout the body, blocking small blood vessels. Symptoms may include chest pain, shortness of breath, leg pain, problems speaking, or problems moving parts ...
. Not all instances of a
purpura Purpura () is a condition of red or purple discolored spots on the skin that do not blanch on applying pressure. The spots are caused by bleeding underneath the skin secondary to platelet disorders, vascular disorders, coagulation disorders, ...
-like rash are due to meningococcal septicaemia; other possible causes, such as
idiopathic thrombocytopenic purpura Immune thrombocytopenic purpura (ITP), also known as idiopathic thrombocytopenic purpura or immune thrombocytopenia, is a type of thrombocytopenic purpura defined as an isolated low platelet count with a normal bone marrow in the absence of oth ...
(ITP; a
platelet Platelets, also called thrombocytes (from Greek θρόμβος, "clot" and κύτος, "cell"), are a component of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping, thereby i ...
disorder) and
Henoch–Schönlein purpura Henoch–Schönlein purpura (HSP), also known as IgA vasculitis, is a disease of the skin, mucous membranes, and sometimes other organs that most commonly affects children. In the skin, the disease causes palpable purpura (small, raised areas of b ...
, also need prompt investigation.


Microbiology

''N. meningitidis'' is a
Gram-negative Gram-negative bacteria are bacteria that do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. They are characterized by their cell envelopes, which are composed of a thin peptidoglycan cell wa ...
diplococcus since it has an outer and inner membranes with a thin layer of
peptidoglycan Peptidoglycan or murein is a unique large macromolecule, a polysaccharide, consisting of sugars and amino acids that forms a mesh-like peptidoglycan layer outside the plasma membrane, the rigid cell wall (murein sacculus) characteristic of most ba ...
in between. It is 0.6–1.0 micrometers in size. It tests positive for the enzyme
cytochrome c oxidase The enzyme cytochrome c oxidase or Complex IV, (was , now reclassified as a translocasEC 7.1.1.9 is a large transmembrane protein complex found in bacteria, archaea, and mitochondria of eukaryotes. It is the last enzyme in the respiratory elect ...
.


Habitat

''N. meningitidis'' is a part of the normal nonpathogenic flora in the
nasopharynx The pharynx (plural: pharynges) is the part of the throat behind the mouth and nasal cavity, and above the oesophagus and trachea (the tubes going down to the stomach and the lungs). It is found in vertebrates and invertebrates, though its struct ...
of up to 8–25% of adults. It colonizes and infects only humans, and has never been isolated from other animals. This is thought to result from the bacterium's inability to get iron from sources other than human
transferrin Transferrins are glycoproteins found in vertebrates which bind to and consequently mediate the transport of iron (Fe) through blood plasma. They are produced in the liver and contain binding sites for two Fe3+ ions. Human transferrin is encod ...
and
lactoferrin Lactoferrin (LF), also known as lactotransferrin (LTF), is a multifunctional protein of the transferrin family. Lactoferrin is a globular glycoprotein with a molecular mass of about 80 kDa that is widely represented in various secretory fluids, s ...
.


Subtypes

Disease-causing strains are classified according to the
antigen In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune respon ...
ic structure of their
polysaccharide Polysaccharides (), or polycarbohydrates, are the most abundant carbohydrates found in food. They are long chain polymeric carbohydrates composed of monosaccharide units bound together by glycosidic linkages. This carbohydrate can react with w ...
capsule. Serotype distribution varies markedly around the world. Among the 13 identified capsular types of ''N. meningitidis'', six (A, B, C, W135, X, and Y) account for most disease cases worldwide. Type A has been the most prevalent in Africa and Asia, but is rare/practically absent in North America. In the United States, serogroup B is the predominant cause of disease and mortality, followed by serogroup C. The multiple subtypes have hindered development of a universal vaccine for meningococcal disease.


Pathogenesis


Virulence

Lipooligosaccharide (LOS) is a component of the outer membrane of ''N. meningitidis''. This acts as an
endotoxin Lipopolysaccharides (LPS) are large molecules consisting of a lipid and a polysaccharide that are bacterial toxins. They are composed of an O-antigen, an outer core, and an inner core all joined by a covalent bond, and are found in the outer m ...
and is responsible for
septic shock Septic shock is a potentially fatal medical condition that occurs when sepsis, which is organ injury or damage in response to infection, leads to dangerously low blood pressure and abnormalities in cellular metabolism. The Third International C ...
and hemorrhage due to the destruction of red blood cells. Other virulence factors include a polysaccharide capsule which prevents host
phagocytosis Phagocytosis () is the process by which a cell uses its plasma membrane to engulf a large particle (≥ 0.5 μm), giving rise to an internal compartment called the phagosome. It is one type of endocytosis. A cell that performs phagocytosis is ...
and aids in evasion of the host immune response. Adhesion is another key virulence strategy to successfully invade host cell. There are several known proteins that are involved in adhesion and invasion, or mediate interactions with specific host cell receptors. These include the Type IV pilin adhesin which mediates attachment of the bacterium to the
epithelial cells Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellu ...
of the
nasopharynx The pharynx (plural: pharynges) is the part of the throat behind the mouth and nasal cavity, and above the oesophagus and trachea (the tubes going down to the stomach and the lungs). It is found in vertebrates and invertebrates, though its struct ...
, surface-exposed Opa and Opc proteins which mediate interactions with specific host cell receptors, and NadA which is involved in adhesion. Pathogenic meningococci that have invaded into the bloodstream must be able to survive in the new niche, this is facilitated by acquisition and utilisation of iron (FetA and Hmbr), resisting intracellular oxidative killing by producing
catalase Catalase is a common enzyme found in nearly all living organisms exposed to oxygen (such as bacteria, plants, and animals) which catalyzes the decomposition of hydrogen peroxide to water and oxygen. It is a very important enzyme in protecting t ...
and
superoxide dismutase Superoxide dismutase (SOD, ) is an enzyme that alternately catalyzes the dismutation (or partitioning) of the superoxide () radical into ordinary molecular oxygen (O2) and hydrogen peroxide (). Superoxide is produced as a by-product of oxygen ...
and ability to avoid
complement A complement is something that completes something else. Complement may refer specifically to: The arts * Complement (music), an interval that, when added to another, spans an octave ** Aggregate complementation, the separation of pitch-clas ...
mediated killing (fHbp). Meningococci produce an IgA protease, an enzyme that cleaves IgA class antibodies and thus allows the bacteria to evade a subclass of the humoral immune system. A hypervirulent strain was discovered in China. Its impact is yet to be determined.


Complement inhibition

Factor H binding protein (fHbp) that is exhibited in ''N. meningitidis'' and some commensal species is the main inhibitor of the
alternative complement pathway The alternative pathway is a type of cascade reaction of the complement system and is a component of the innate immune system, a natural defense against infections. The alternative pathway is one of three complement pathways that opsonize and ...
. fHbp protects meningococci from complement-mediated death in human serum experiments, but has also been shown to protect meningococci from antimicrobial peptides ''in vitro''. Factor H binding protein is key to the pathogenesis of ''N. meningitidis'', and is, therefore, important as a potential vaccine candidate. Porins are also an important factor for complement inhibition for both pathogenic and commensal species. Porins are important for nutrient acquisition. Porins are also recognized by
TLR2 Toll-like receptor 2 also known as TLR2 is a protein that in humans is encoded by the ''TLR2'' gene. TLR2 has also been designated as CD282 (cluster of differentiation 282). TLR2 is one of the toll-like receptors and plays a role in the immune sys ...
, they bind complement factors (
C3b C3b is the larger of two elements formed by the cleavage of complement component 3, and is considered an important part of the innate immune system. C3b is potent in opsonization: tagging pathogens, immune complexes (antigen-antibody), and apoptot ...
, C4b, factor H, and C4bp (complement factor 4b-binding protein)). Cooperation with pili for CR3-mediated internalization is another function of porins. Ability to translocate into host cells and modulate
reactive oxygen species In chemistry, reactive oxygen species (ROS) are highly reactive chemicals formed from diatomic oxygen (). Examples of ROS include peroxides, superoxide, hydroxyl radical, singlet oxygen, and alpha-oxygen. The reduction of molecular oxygen () p ...
production and apoptosis is made possible by porins, as well. Strains of the same species can express different porins.


Genome

At least 8 complete genomes of ''Neisseria meningitidis'' strains have been determined which encode about 2,100 to 2,500 proteins. The genome of strain MC58 (serogroup B) has 2,272,351-base pairs. When sequenced in 2000, it was found to contain 2158 open reading frames (ORFs). Of these, a biological function was predicted for 1158 (53.7%). There were three major islands of horizontal DNA transfer found. Two encode proteins involved in pathogenicity. The third island only codes for hypothetical proteins. They also found more genes that undergo
phase variation In biology, phase variation is a method for dealing with rapidly varying environments without requiring random mutation. It involves the variation of protein expression, frequently in an on-off fashion, within different parts of a bacterial populati ...
than any pathogen then known. Phase variation is a mechanism that helps the pathogen to evade the
immune system The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...
of the host. The genome size of strain H44/76 is 2.18 Mb, and encodes 2,480 open reading frames (ORFs), compared to 2.27 Mb and 2,465 ORFs for MC58. Both strains have a GC content of 51.5%. A comparison with MC58 showed that four genes are uniquely present in H44/76 and nine genes are only present in MC58. Of all ORFs in H44/76, 2,317 (93%) show more than 99% sequence identity. The complete genome sequence of strain NMA510612 (serogroup A) consists of one circular chromosome with a size of 2,188,020 bp, and the average GC content is 51.5%. The chromosome is predicted to possess 4 rRNA operons, 163 insertion elements (IS), 59 tRNAs, and 2,462 ORFs. There is a public database available for ''N. meningitidis'' core genome multilocus sequence typing (cMILST). Available at: https://pubmlst.org/bigsdb?db=pubmlst_neisseria_seqdef


Genetic transformation

Genetic transformation is the process by which a recipient bacterial cell takes up DNA from a neighboring cell and integrates this DNA into the recipient's genome by recombination. In ''N. meningitidis'', DNA transformation requires the presence of short DNA sequences (9–10 mers residing in
coding region The coding region of a gene, also known as the coding sequence (CDS), is the portion of a gene's DNA or RNA that codes for protein. Studying the length, composition, regulation, splicing, structures, and functions of coding regions compared to n ...
s) of the donor DNA. These sequences are called DNA uptake sequences (DUSs). Specific recognition of these sequences is mediated by a type IV pilin. In ''N. meningitidis'' DUSs occur at a significantly higher density in genes involved in
DNA repair DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA d ...
and recombination (as well as in restriction-modification and replication) than in other annotated gene groups. The over-representation of DUS in DNA repair and recombination genes may reflect the benefit of maintaining the integrity of the DNA repair and recombination machinery by preferentially taking up genome maintenance genes, that could replace their damaged counterparts in the recipient cell. ''N. meningititis'' colonizes the nasopharyngeal
mucosa A mucous membrane or mucosa is a membrane that lines various cavities in the body of an organism and covers the surface of internal organs. It consists of one or more layers of epithelial cells overlying a layer of loose connective tissue. It i ...
, which is rich in
macrophage Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer ce ...
s. Upon their activation, macrophages produce
superoxide In chemistry, a superoxide is a compound that contains the superoxide ion, which has the chemical formula . The systematic name of the anion is dioxide(1−). The reactive oxygen ion superoxide is particularly important as the product of t ...
(O2) and
hydrogen peroxide Hydrogen peroxide is a chemical compound with the formula . In its pure form, it is a very pale blue liquid that is slightly more viscous than water. It is used as an oxidizer, bleaching agent, and antiseptic, usually as a dilute solution (3 ...
(H2O2). Thus ''N. meningitidis'' is likely to encounter
oxidative stress Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage. Disturbances in the normal ...
during its life cycle. Consequently, an important benefit of genetic transformation to ''N. meningitidis'' may be the maintenance of the recombination and repair machinery of the cell that removes oxidative DNA damages such as those caused by reactive oxygen. This is consistent with the more general idea that transformation benefits bacterial
pathogen In biology, a pathogen ( el, πάθος, "suffering", "passion" and , "producer of") in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a g ...
s by facilitating repair of DNA damages produced by the oxidative defenses of the host during infection. Meningococci population is extensively diverse genetically, this is due to
horizontal gene transfer Horizontal gene transfer (HGT) or lateral gene transfer (LGT) is the movement of genetic material between unicellular and/or multicellular organisms other than by the ("vertical") transmission of DNA from parent to offspring (reproduction). H ...
s while in the nasophanrynx. Gene transfer can occur within and between genomes of Neisseria species, and it is the main mechanism of acquiring new traits. This is facilitated by the natural competence of the meningococci to take up foreign DNA. The commensal species of Neisseria can act as a reservoir of genes that can be acquired, for example, this is how capsule switching can occur as a means of hiding from the immune system. An invasive ''N. meningitidis'' strain of serogroup C broke out in Nigeria in 2013 - the strain was a new sequence type, ST-10217 determined by multilocus sequence typing. It was determined that a commensal strain of ''N. meningitidis'' acquired an 8-kb prophage, the meningococcal disease-associated island (MDAΦ), previously associated with hyper-invasiveness; and the full serogroup C capsule operon, thus becoming a hypervirulent strain. This illustrates how hypervirulent strains can arise from non-pathgenic strains due to the high propensity of gene transfers and DNA uptake by ''N. meningitidis''.


Diagnosis

A small amount of
cerebrospinal fluid Cerebrospinal fluid (CSF) is a clear, colorless body fluid found within the tissue that surrounds the brain and spinal cord of all vertebrates. CSF is produced by specialised ependymal cells in the choroid plexus of the ventricles of the ...
(CSF) is sent to the laboratory as soon as possible for analysis. The diagnosis is suspected, when
Gram-negative Gram-negative bacteria are bacteria that do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. They are characterized by their cell envelopes, which are composed of a thin peptidoglycan cell wa ...
diplococci are seen on
Gram stain In microbiology and bacteriology, Gram stain (Gram staining or Gram's method), is a method of staining used to classify bacterial species into two large groups: gram-positive bacteria and gram-negative bacteria. The name comes from the Danish b ...
of a centrifuged sample of CSF; sometimes they are located inside
white blood cells White blood cells, also called leukocytes or leucocytes, are the cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and derived from mult ...
. The microscopic identification takes around 1–2 hours after specimen arrival in the laboratory. The
gold standard A gold standard is a monetary system in which the standard economic unit of account is based on a fixed quantity of gold. The gold standard was the basis for the international monetary system from the 1870s to the early 1920s, and from th ...
of diagnosis is microbiological isolation of ''N. meningitidis'' by growth from a sterile body fluid, which could be CSF or blood. Diagnosis is confirmed when the organism has grown, most often on a chocolate agar plate, but also on Thayer-Martin agar. To differentiate any bacterial growth from other species a small amount of a
bacterial colony In biology, a colony is composed of two or more conspecific individuals living in close association with, or connected to, one another. This association is usually for mutual benefit such as stronger defense or the ability to attack bigger prey. ...
is tested for oxidase,
catalase Catalase is a common enzyme found in nearly all living organisms exposed to oxygen (such as bacteria, plants, and animals) which catalyzes the decomposition of hydrogen peroxide to water and oxygen. It is a very important enzyme in protecting t ...
for which all clinically relevant ''Neisseria'' show a positive reaction, and the
carbohydrates In organic chemistry, a carbohydrate () is a biomolecule consisting of carbon (C), hydrogen (H) and oxygen (O) atoms, usually with a hydrogen–oxygen atom ratio of 2:1 (as in water) and thus with the empirical formula (where ''m'' may or m ...
maltose } Maltose ( or ), also known as maltobiose or malt sugar, is a disaccharide formed from two units of glucose joined with an α(1→4) bond. In the isomer isomaltose, the two glucose molecules are joined with an α(1→6) bond. Maltose is the tw ...
,
sucrose Sucrose, a disaccharide, is a sugar composed of glucose and fructose subunits. It is produced naturally in plants and is the main constituent of white sugar. It has the molecular formula . For human consumption, sucrose is extracted and refine ...
, and
glucose Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, u ...
, in which ''N. meningitidis'' will ferment that is, utilize the glucose and maltose. Finally,
serology Serology is the scientific study of serum and other body fluids. In practice, the term usually refers to the diagnostic identification of antibodies in the serum. Such antibodies are typically formed in response to an infection (against a given mic ...
determines the
subgroup In group theory, a branch of mathematics, given a group ''G'' under a binary operation ∗, a subset ''H'' of ''G'' is called a subgroup of ''G'' if ''H'' also forms a group under the operation ∗. More precisely, ''H'' is a subgroup ...
of the ''N. meningitidis'', which is important for epidemiological surveillance purposes; this may often only be done in specialized laboratories. The above tests take a minimum of 48–72 hours
turnaround time Turnaround time (TAT) is the amount of time taken to complete a process or fulfill a request. The concept thus overlaps with lead time and can be contrasted with cycle time. Meaning in computing In computing, turnaround time is the total time t ...
for growing the organism, and up to a week more for serotyping. Growth can and often does fail, either because antibiotics have been given preemptively, or because specimens have been inappropriately transported, as the organism is extremely susceptible to antibiotics and fastidious in its temperature, and growth medium requirements.
Polymerase chain reaction The polymerase chain reaction (PCR) is a method widely used to rapidly make millions to billions of copies (complete or partial) of a specific DNA sample, allowing scientists to take a very small sample of DNA and amplify it (or a part of it) ...
(PCR) tests where available, mostly in industrialized countries, have been increasingly used; PCR can rapidly identify the organism, and works even after antibiotics have been given.


Prevention

All recent contacts of the infected patient over the 7 days before onset should receive medication to prevent them from contracting the infection. This especially includes young children and their child caregivers or nursery-school contacts, as well as anyone who had direct exposure to the patient through kissing, sharing utensils, or medical interventions such as mouth-to-mouth resuscitation. Anyone who frequently ate, slept or stayed at the patient's home during the 7 days before the onset of symptom, or those who sat beside the patient on an airplane flight or classroom for 8 hours or longer, should also receive chemoprophylaxis. The agent of choice is usually oral
rifampicin Rifampicin, also known as rifampin, is an ansamycin antibiotic used to treat several types of bacterial infections, including tuberculosis (TB), ''Mycobacterium avium'' complex, leprosy, and Legionnaires’ disease. It is almost always used t ...
for a few days. Receiving a dose of the ''Meningococcal vaccine'' before traveling to a country in the "meningitis belt" or having a booster meningitis vaccine, normally five years apart could prevent someone from getting an infection from the pathogen.


Vaccination


United States

A number of vaccines are available in the U.S. to prevent meningococcal disease. Some of the vaccines cover serogroup B, while others cover A, C, W, and Y. The
Centers for Disease Control and Prevention The Centers for Disease Control and Prevention (CDC) is the national public health agency of the United States. It is a United States federal agency, under the Department of Health and Human Services, and is headquartered in Atlanta, Georg ...
(CDC) recommends all teenagers receive MenACWY vaccine and booster, with optional MenB. MenACWY and MenB are also recommended for people of other ages with various medical conditions and social risk factors. A meningococcal polysaccharide vaccine (MPSV4) has been available since the 1970s and is the only meningococcal vaccine licensed for people older than 55. MPSV4 may be used in people 2–55 years old if the MCV4 vaccines are not available or contraindicated. Two meningococcal
conjugate vaccine A conjugate vaccine is a type of subunit vaccine which combines a weak antigen with a strong antigen as a carrier so that the immune system has a stronger response to the weak antigen. Vaccines are used to prevent diseases by invoking an immun ...
s (MCV4) are licensed for use in the U.S. The first conjugate vaccine was licensed in 2005, the second in 2010. Conjugate vaccines are the preferred vaccine for people 2 through 55 years of age. It is indicated in those with impaired immunity, such as
nephrotic syndrome Nephrotic syndrome is a collection of symptoms due to kidney damage. This includes protein in the urine, low blood albumin levels, high blood lipids, and significant swelling. Other symptoms may include weight gain, feeling tired, and foamy ...
or
splenectomy A splenectomy is the surgical procedure that partially or completely removes the spleen. The spleen is an important organ in regard to immunological function due to its ability to efficiently destroy encapsulated bacteria. Therefore, removal of ...
. In June 2012, the U.S.
Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...
(FDA) approved a combination vaccine against two types of meningococcal diseases and Hib disease for infants and children 6 weeks to 18 months old. The vaccine, Menhibrix, was designed to prevent disease caused by ''Neisseria meningitidis'' serogroups C and Y, and ''Haemophilus influenzae'' type b (Hib). It was the first meningococcal vaccine that could be given to infants as young as six weeks old. In October 2014 the FDA approved the first vaccine effective against serogroup B, named Trumenba, for use in 10- to 25-year-old individuals.


Africa

In 2010, the Meningitis Vaccine Project introduced a vaccine called MenAfriVac in the
African meningitis belt The African meningitis belt is a region in sub-Saharan Africa where the rate of incidence of meningitis is very high. It extends from Senegal to Ethiopia, and the primary cause of meningitis in the belt is ''Neisseria meningitidis''. The belt was ...
. It was made by generic drug maker
Serum Institute of India Serum Institute of India (SII) is an Indian biotechnology and biopharmaceuticals company, based in Pune. It is the world's largest manufacturer of vaccines. It was founded by Cyrus Poonawalla in 1966 and is a part of Cyrus Poonawalla Group. ...
and cost 50 U.S. cents per injection. Beginning in
Burkina Faso Burkina Faso (, ; , ff, 𞤄𞤵𞤪𞤳𞤭𞤲𞤢 𞤊𞤢𞤧𞤮, italic=no) is a landlocked country in West Africa with an area of , bordered by Mali to the northwest, Niger to the northeast, Benin to the southeast, Togo and Ghana t ...
in 2010, it has been given to 215 million people across
Benin Benin ( , ; french: Bénin , ff, Benen), officially the Republic of Benin (french: République du Bénin), and formerly Dahomey, is a country in West Africa. It is bordered by Togo to the west, Nigeria to the east, Burkina Faso to the nort ...
,
Cameroon Cameroon (; french: Cameroun, ff, Kamerun), officially the Republic of Cameroon (french: République du Cameroun, links=no), is a country in west-central Africa. It is bordered by Nigeria to the west and north; Chad to the northeast; the ...
,
Chad Chad (; ar, تشاد , ; french: Tchad, ), officially the Republic of Chad, '; ) is a landlocked country at the crossroads of North and Central Africa. It is bordered by Libya to the north, Sudan to the east, the Central African Republic ...
,
Ivory Coast Ivory Coast, also known as Côte d'Ivoire, officially the Republic of Côte d'Ivoire, is a country on the southern coast of West Africa. Its capital is Yamoussoukro, in the centre of the country, while its largest city and economic centre i ...
,
Ethiopia Ethiopia, , om, Itiyoophiyaa, so, Itoobiya, ti, ኢትዮጵያ, Ítiyop'iya, aa, Itiyoppiya officially the Federal Democratic Republic of Ethiopia, is a landlocked country in the Horn of Africa. It shares borders with Eritrea to the ...
,
Ghana Ghana (; tw, Gaana, ee, Gana), officially the Republic of Ghana, is a country in West Africa. It abuts the Gulf of Guinea and the Atlantic Ocean to the south, sharing borders with Ivory Coast in the west, Burkina Faso in the north, and Tog ...
,
Mali Mali (; ), officially the Republic of Mali,, , ff, 𞤈𞤫𞤲𞥆𞤣𞤢𞥄𞤲𞤣𞤭 𞤃𞤢𞥄𞤤𞤭, Renndaandi Maali, italics=no, ar, جمهورية مالي, Jumhūriyyāt Mālī is a landlocked country in West Africa. Ma ...
,
Niger ) , official_languages = , languages_type = National languagesMauritania Mauritania (; ar, موريتانيا, ', french: Mauritanie; Berber: ''Agawej'' or ''Cengit''; Pulaar: ''Moritani''; Wolof: ''Gànnaar''; Soninke:), officially the Islamic Republic of Mauritania ( ar, الجمهورية الإسلامية ...
,
Nigeria Nigeria ( ), , ig, Naìjíríyà, yo, Nàìjíríà, pcm, Naijá , ff, Naajeeriya, kcg, Naijeriya officially the Federal Republic of Nigeria, is a country in West Africa. It is situated between the Sahel to the north and the Gulf o ...
,
Senegal Senegal,; Wolof: ''Senegaal''; Pulaar: 𞤅𞤫𞤲𞤫𞤺𞤢𞥄𞤤𞤭 (Senegaali); Arabic: السنغال ''As-Sinighal'') officially the Republic of Senegal,; Wolof: ''Réewum Senegaal''; Pulaar : 𞤈𞤫𞤲𞤣𞤢𞥄𞤲𞤣𞤭 ...
,
Sudan Sudan ( or ; ar, السودان, as-Sūdān, officially the Republic of the Sudan ( ar, جمهورية السودان, link=no, Jumhūriyyat as-Sūdān), is a country in Northeast Africa. It shares borders with the Central African Republic t ...
,
Togo Togo (), officially the Togolese Republic (french: République togolaise), is a country in West Africa. It is bordered by Ghana to the west, Benin to the east and Burkina Faso to the north. It extends south to the Gulf of Guinea, where its c ...
and
Gambia The Gambia,, ff, Gammbi, ar, غامبيا officially the Republic of The Gambia, is a country in West Africa. It is the smallest country within mainland AfricaHoare, Ben. (2002) ''The Kingfisher A-Z Encyclopedia'', Kingfisher Publicatio ...
. The vaccination campaign has resulted in near-elimination of serogroup A meningitis from the participating countries.


Treatment

Persons with confirmed ''N. meningitidis'' infection should be hospitalized immediately for treatment with antibiotics. Because meningococcal disease can disseminate very rapidly, a single dose of intramuscular antibiotic is often given at the earliest possible opportunity, even before hospitalization, if disease symptoms look suspicious enough. Third-generation
cephalosporin The cephalosporins (sg. ) are a class of β-lactam antibiotics originally derived from the fungus ''Acremonium'', which was previously known as ''Cephalosporium''. Together with cephamycins, they constitute a subgroup of β-lactam antibiotics ...
antibiotics (i.e.
cefotaxime Cefotaxime is an antibiotic used to treat a number of bacterial infections in human, other animals and plant tissue culture. Specifically in humans it is used to treat joint infections, pelvic inflammatory disease, meningitis, pneumonia, urinar ...
,
ceftriaxone Ceftriaxone, sold under the brand name Rocephin, is a third-generation cephalosporin antibiotic used for the treatment of a number of bacterial infections. These include middle ear infections, endocarditis, meningitis, pneumonia, bone and join ...
) should be used to treat a suspected or culture-proven meningococcal infection before antibiotic susceptibility results are available. Clinical practice guidelines endorse empirical treatment in the event a
lumbar puncture Lumbar puncture (LP), also known as a spinal tap, is a medical procedure in which a needle is inserted into the spinal canal, most commonly to collect cerebrospinal fluid (CSF) for diagnostic testing. The main reason for a lumbar puncture is ...
to collect
cerebrospinal fluid Cerebrospinal fluid (CSF) is a clear, colorless body fluid found within the tissue that surrounds the brain and spinal cord of all vertebrates. CSF is produced by specialised ependymal cells in the choroid plexus of the ventricles of the ...
(CSF) for laboratory testing cannot first be performed. Antibiotic treatment may affect the results of microbiology tests, but a diagnosis may be made on the basis of blood-cultures and clinical examination.


Epidemiology

''N. meningitidis'' is a major cause of illness, developmental impairment and death during childhood in industrialized countries and has been responsible for epidemics in Africa and in Asia. Every year, about 2,500 to 3,500 people become infected with ''N. meningitidis'' in the US, with a frequency of about 1 in 100,000. Children younger than 5 years are at greatest risk, followed by teenagers of high school age. Rates in the
African meningitis belt The African meningitis belt is a region in sub-Saharan Africa where the rate of incidence of meningitis is very high. It extends from Senegal to Ethiopia, and the primary cause of meningitis in the belt is ''Neisseria meningitidis''. The belt was ...
were as high as 1 in 1,000 to 1 in 100 before introduction of a vaccine in 2010. The incidence of meningococcal disease is highest among infants (children younger than 1-year-old) whose immune system is relatively immature. In industrialized countries there is a second peak of incidence in young adults, who are congregating closely, living in dormitories or smoking. Vaccine development is ongoing. It is spread through saliva and other respiratory secretions during coughing, sneezing, kissing, and chewing on toys. Inhalation of respiratory droplets from a
carrier Carrier may refer to: Entertainment * ''Carrier'' (album), a 2013 album by The Dodos * ''Carrier'' (board game), a South Pacific World War II board game * ''Carrier'' (TV series), a ten-part documentary miniseries that aired on PBS in April 20 ...
which may be someone who is themselves in the early stages of disease can
transmit Transmit is a file transfer client program for macOS. Developed by Panic, Transmit is shareware. After a seven-day trial period, the product can only be used for seven-minute sessions until it has been purchased. Originally built as an FTP clien ...
the bacteria. Close contact with a carrier is the predominant
risk factor In epidemiology, a risk factor or determinant is a variable associated with an increased risk of disease or infection. Due to a lack of harmonization across disciplines, determinant, in its more widely accepted scientific meaning, is often u ...
. Other risk factors include a weakened general or local immune response, such as a recent upper respiratory infection, smoking, and
complement deficiency Complement deficiency is an immunodeficiency of absent or suboptimal functioning of one of the complement system proteins. Because of redundancies in the immune system, many complement disorders are never diagnosed. Some studies estimate that less ...
. The
incubation period Incubation period (also known as the latent period or latency period) is the time elapsed between exposure to a pathogenic organism, a chemical, or radiation, and when symptoms and signs are first apparent. In a typical infectious disease, the in ...
is short, from 2 to 10 days. In susceptible individuals, ''N. meningitidis'' may invade the bloodstream and cause a systemic infection, sepsis,
disseminated intravascular coagulation Disseminated intravascular coagulation (DIC) is a condition in which blood clots form throughout the body, blocking small blood vessels. Symptoms may include chest pain, shortness of breath, leg pain, problems speaking, or problems moving parts ...
, breakdown of circulation, and
septic shock Septic shock is a potentially fatal medical condition that occurs when sepsis, which is organ injury or damage in response to infection, leads to dangerously low blood pressure and abnormalities in cellular metabolism. The Third International C ...
.


History

In 1884
Ettore Marchiafava Ettore Marchiafava (3 January 1847 – 22 October 1935) was an Italian physician, pathologist and neurologist. He spent most of his career as professor of medicine at the University of Rome (now Sapienza Università di Roma). His works on malar ...
and
Angelo Celli Angelo Celli (25 March 1857 – 2 November 1914) was an Italian physician, hygienist, parasitologist and philanthropist known for his pioneering work on the malarial parasite and control of malaria. He was Professor of Hygiene at the Universit ...
first observed the bacterium inside cells in the
cerebral spinal fluid Cerebrospinal fluid (CSF) is a clear, colorless body fluid found within the tissue that surrounds the brain and spinal cord of all vertebrates. CSF is produced by specialised ependymal cells in the choroid plexus of the ventricles of the ...
(CSF). In 1887 Anton Weichselbaum isolated the bacterium from the CSF of patients with bacterial meningitis. He named the bacterium ''Diplococcus intracellularis meningitidis''.


Biotechnology

Components from ''Neisseria meningitidis'' are being harnessed in biotechnology. Its Cas9 enzyme is a useful tool in
CRISPR gene editing CRISPR gene editing (pronounced "crisper") is a genetic engineering technique in molecular biology by which the genomes of living organisms may be modified. It is based on a simplified version of the bacterial CRISPR-Cas9 antiviral defense syst ...
because the enzyme is small and has distinct targeting features to the commonly used enzyme from ''
Streptococcus pyogenes ''Streptococcus pyogenes'' is a species of Gram-positive, aerotolerant bacteria in the genus '' Streptococcus''. These bacteria are extracellular, and made up of non-motile and non-sporing cocci (round cells) that tend to link in chains. They ...
''. The cell-surface protein FrpC from ''Neisseria meningitidis'' has been engineered to allow covalent coupling between proteins, because it generates a reactive anhydride when exposed to calcium. The bacterium also expresses unique enzymes able to cleave
IgA Iga may refer to: Arts and entertainment * Ambush at Iga Pass, a 1958 Japanese film * Iga no Kagemaru, Japanese manga series * Iga, a set of characters from the Japanese novel '' The Kouga Ninja Scrolls'' Biology * ''Iga'' (beetle), a g ...
antibodies.


See also

* DNA uptake sequence DNA taken up by Neisseria * NmVac4-A/C/Y/W-135 polysaccharide vaccine *
Sara Branham Matthews Sara Elizabeth Branham Matthews (1888–1962) was an American microbiologist and physician best known for her research into the isolation and treatment of '' Neisseria meningitidis'', a causative organism of meningitis. Biography Branham wa ...
microbiologist * Shwartzman phenomenon *
Sepsis Sepsis, formerly known as septicemia (septicaemia in British English) or blood poisoning, is a life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage is follo ...


References


External links

*
Type strain of ''Neisseria meningitidis'' at Bac''Dive'' - the Bacterial Diversity Metadatabase
{{Taxonbar, from=Q154625 Gram-negative bacteria Pathogenic bacteria Polysaccharide encapsulated bacteria Neisseriales Bacteria described in 1901