Meningococcemia

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Cafer Zorkun, M.D., Ph.D. [2]; Ammu Susheela, M.D. [3]

Meningococcemia is the presence of Neisseria meningitidis‘ (also known as meningococcus), a severe bacterial infection, in the blood stream. It is demonstrated by blood culture. The disease is hard to identify as it can appear in several different forms, depending on which part of the body the bacteria invades. Neisseria meningitides is a gram-negative diplococcus. The bacteria is known to cause: meningitis, septicaemia, pneumonia, and even rarely urethritis. Early recognition and treatment of those exposed to meningococcus is extremely important in order to prevent serious illness like shock, DIC, multiorgan failure or death.

Historical reports indicate that meningococci was first reported in 1805. Since then, for more than 2 hundred years, meningococcus has been causing a high degree of morbidity and mortality. It usually appears to be sporadic but reports of outbreak have been reported from different parts of the world, especially in the Sub-Saharan African belt. Outbreak usually happens in closed communities, such as: schools, colleges and prisons.

13 serotypes of meningococci have been isolated based on their polysaccharide capsule; they are also classified according to outer membrane protein. Out of these thirteen, five of them cause clinically severe diseases.

Meningococcal infection is caused by Neisseria meningitidis and it spreads through respiratory and throat secretions. Once it gets absorbed by endocytosis into the body, it gets seeded in skin , meninges and other organs; it causes a variety of clinical manifestation from meningitis to septic shock. The meningococcal lipopolysaccharide is an important factor in infection; host factors such as Toll Like Receptor (TLR) and inflammatory cytokines (IL-6) play an important role in the pathogenesis of the disease.

Meningococcemia is caused by a bacteria called Neisseria meningitidis. The bacteria frequently lives in a person’s upper respiratory tract without causing any visible signs of illness. The bacteria can spread from person to person interaction through respiratory droplets; for example, to be around an already infected individual, during the time that he or she sneezes or coughs, can cause an individual to become infected. Family members and those closely exposed to someone with the condition are at increased risk. The infection occurs more frequently in the winter and early spring.

Meningococcemia must be differentiated from other diseases that cause neurological symptoms, such as: brain abscess, encephalitis, delirium tremens, brain tumor, and subarachnoid hemorrhage. The rash component of meningococcemia must be differentiated from other illnesses causing skin rash, such as: chickenpox, herpes zoster, and erythema multiforme.

Meningococcus occurs throughout the year, however, the incidence is highest in late winter and early spring. It is the second most common community acquired bacterial infection. The highest incidence worldwide is in Sub-Saharan Africa called meningitis belt. Children are most affected by this disease.

Risk factors of meningococcemia include: infants and old age groups ; closed communities; winter and early spring season; complement deficiency; asplenia; and travel to endemic regions, especially to the Sub-Saharan African meningitis belt.

Routine screening is not recommended for meningococcemia.

Neisseria meningitidis bacteria can cause problems ranging from meningitis fatal to septicemia. The symptoms of meningitis appear within 3-7 days of exposure and present with fever and signs of bacterial meningitis. If septicemia occurs, it can be very fatal and the patient dies in few hours. In non fatal conditions they develop disabilities like arthritis, gangrene, Disseminated intravascular coagulopathy and cutaneous vasculitis. The outcome is uncertain in septicemic patients but prognosis is good in non septicemic patients with early intervention and treatment.

Every child with purpuric rash and high fever should be treated as meningococcemia until proven otherwise. The history suggest patient with high fever, rash, headache, myalgia and stiff neck.Non-suppurative pharyngitis is a rare presentation.

Physical examination may shows fever, hypotension, petechial rash, conjuctival congestion, nuchal rigidity, seizures, edema, hepatosplenomegaly, dyspnea and rales.

Meningococci is usually identified from blood or CSF analysis. Aspiration or skin biopsy of the rash yield meningococci. CSF analysis usually shows increased protein, low glucose and increased number of neutrophils.

Meningococcemia is a medical emergency and effective antibiotics should be administered promptly to patients suspected of having meningococcal disease. Multiple antimicrobial agents, including penicillins or third generation cephalosporin(eg. Ceftriaxone), are effective against N. meningitidis. Additional therapy may be needed, such as breathing support, fluid resuscitation, and wound care.

Primary prevention of meningococcemia includes vaccination and chemo prophylaxis. There are mainly 2 different types of vaccine namely polysaccharide and conjugate vaccine. Chemoprophylaxis is mainly with rifampin, ceftriaxone, ciprofloxacin and azithromycin.

Cost effective analysis study has indicated that a 2-dose series at ages 11 years and 16 years has a similar cost-effectiveness compared with moving the single dose to age 15 years or maintaining the single dose at 11 years.

Future investigational therapies are showing promising results where 2 new vaccines were being developed against serogroup B and 3 new types of antigen have been found to be useful in making vaccines more potent.

• CDC.gov Meningococcal Disease

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Ammu Susheela, M.D. [2], Usama Talib, BSc, MD [3]

The historical reports indicate that meningococci was first reported in 1805. SInce then for more than 2 hundred years, meningococcus have been causing a high degree of morbidity and mortality. It usually appear as sporadic but reports of outbreak have been reported from different parts of the world especially Sub Saharan African belt. Outbreak usually happens in close communities like schools, colleges and prisons.

• Records indicate that the first case of meningococcal meningitis was described in Geneva in 1805.^[1]
• Another case was reported in New England, New Bedford, Massachusetts in 1806.^[2]
• The causative agent was described as intracellular oval cocci in a cerebrospinal fluid sample by Marchiafava and Celli in 1884.
• The organism was isolated by Anton Weischselbaum in 1887 and he gave the term diplococcus intracellularis meningitidis.
• From then on for more than 2 hundred years,meningococcus has caused high rates of morbidity and mortality all around the world.
• No reports of outbreaks have been reported prior to 1806.
• The first meningococcal epidemics occurred in early 1900s in sub saharan Africa.

• Usually the menigococcal meningitis cases appear sporadic. Very rarely they can occur as an outbreaks and the outbreaks are usually found in communities like schools, colleges, prisons and such close populations.
• In temperate regions the number of cases increases in winter and spring. Serogroups B and C together account for a large majority of cases in Europe and America.
• Several local outbreaks due to Neisseria meningitidis serogroup C have been reported in Canada and the United States (1992-93) and in Spain (1995-97).
• In 1998 2725 cases were reported in US and 155 cases in Canada.
• In 1995-1998 in US

• 33% were due to serotype B
• 28% due to serotype C
• 34% due to serotype Y

• In Canada during 1995-98

• 47% were due to serotype B
• 40% were due to serotype C
• 10% due to serotype Y^[3]

• Major African epidemics are associated with Neisseria meningitidis serogroup A, which is usually the cause of meningococcal disease in Asia.
• In 2000 and 2001 several hundred pilgrims attending the Hajj in Saudi Arabia were infected with Neisseria meningitidis W.
• In 2002, Neisseria meningitidis W emerged in Burkina Faso, striking 13,000 people and killing 1,500.
• In 2008, subsaharan Africa with Nigeria, faced an outbreak of Meningococcal meningitis in particllarly in the northern states.^[4]
• In 2017, an outbreak afected Nigeria again, killing almost 500 individuals.^[5]

• Serotype C was identified as the primary cause of this outbreak

• Epidemics have been happening in Africa for more than 100 years.
• The disease is usually found in Sub Saharan meningitis belt.
• Epidemics there occur in the dry season (December to June), ending during the intervening rainy season.
• Epidemics usually take place in irregular cycles every 5-12 years.
• 80-85% of all reported case is by Serogroup A meningococci.
• In 2002 there was a major outbreak of meningococcal disease in Burkina Faso with about 80% of cases due to serogroup W.
• Between 1988 and 1997, 704,000 cases and more than 100,000 deaths were reported in Africa, some 20,000 occurring in 1996, the largest epidemic year ever recorded.
• Between 1998 and 2002, African countries within the meningitis belt reported more than 224,000 new cases of meningococcal disease.
• Depicted below is a meningococcal belt in Africa where historic perspective reports numerous outbreaks.

• Three cases were reported of fluoroquinolone-resistant meningococcal disease in North America. They occurred among residents of the border area of North Dakota and Minnesota during January 2007–January 2008.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Cafer Zorkun, M.D., Ph.D. [2]

13 serotypes of meningococci have been isolated based on their polysacchride capsule out of which five of them causes clinically severe diseases. They are also classified according to outer membrane protein.

• Meningococci are classified by using serologic methods based on the structure of the polysaccharide capsule.
• 13 Serotypes are described based on capsular polysaccharide: A, B, C, D, X, Y, Z, E, W-135, H, I, K, and L.
• Serogroup A usually with epidemics in less developed nations and an attack rate of as high as 500 cases per 100,000 population.
• Serogroup B usually in developed nations with attack rate of 50-100 cases per 100,000 population.
• Serogroup C usually in both developed and less developed populations and an attack rate of up to 500 per 100,000 population.
• Some strains, often those found to cause asymptomatic nasopharyngeal carriage, are not groupable and do not have a capsule.
• Almost all invasive disease is caused by one of five serogroups: A, B, C, Y, and W-135.
• The relative importance of each serogroup depends on geographic location, as well as other factors, such as age. For instance, serogroup A is a major cause of disease in sub-Saharan Africa but is rarely isolated in the United States.
• Meningococci are further classified on the basis of certain outer membrane proteins. Molecular subtyping using specialized laboratory techniques (e.g., pulsed-field gel electrophoresis) can provide useful epidemiologic information.^[1]

• They present with a wide range of clinical conditions from transient bacteremia to rapidly progressing septicemia.
• Most of them develop meningitis as meningococci invade the meninges.
• Meningococcal infections are classified into four different clinical groups based on the following conditions:

• Presence or absence of signs of septic shock.
• Presence or absence of clinical symptoms and laboratory signs of distinct meningitis.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Cafer Zorkun, M.D., Ph.D. [2]; Ammu Susheela, M.D. [3]

Meningococcal infection is caused by Neisseria meningitidis and they spread through respiratory and throat secretions. Once it get absorbed by endocytosis into the body, it get seeded in skin , meninges and other organs and cause a variety of clinical manifestation from meningitis to septicemic shock. The meningococcal lipopolysachride is an important factor in the infection and host factors like Toll like receptor (TLR) and inflammatory cytokines play an important role in the pathogenesis of the disease.

• Meningococcal disease is caused by the bacterium Neisseria meningitidis, also called meningococcus.^[1]
• About 10% of people have this type of bacteria in the back of their nose and throat with no signs or symptoms of disease; this is the carrier state. But sometimes Neisseria meningitidis bacteria can invade the body causing certain illnesses, which are known as meningococcal disease.
• Neisseria meningitidis bacteria are spread through the exchange of respiratory and throat secretions.
• The bacteria are not spread by casual contact or by simply breathing the air where a person with meningococcal disease has been.
• Sometimes Neisseria meningitidis bacteria spread to people who have had close or lengthy contact with a patient with meningococcal disease. People in the same household, roommates, or anyone with direct contact with a patient’s oral secretions, such assaliva, would be considered at increased risk of getting the infection.
• The bacteria attach to and multiply on the mucosal cells of the nasopharynx.
• Adhesive factors like pilli helps to get it attached itself to nonciliated epithelial cells.

• IgA protease, factors that inhibit ciliary activity and polysaccharide capsule enable it to avoid host defence mechanisms.
• Newborn, individuals deficient in terminal components of complement pathway and properdin deficiency have recurrent infections.
• Mutations in mannose binding lecithin gene have increased risk of infections

• Shock is due to lipooligosaccharide which is a potent toxin. This toxin initiates release of inflammatory cytokines, reactive oxygen radicals, prostaglandins, arachidonic acid, complement activated products, platelet aggregating factor, and perhaps nitric oxide.
• In a small proportion (less than 1%) of colonized persons, the organism penetrates the mucosal cells and enters the bloodstream.
• The bacteria spread by way of theblood to many organs. In about 50% of bacteremic persons, the organism crosses the blood–brain barrier into the cerebrospinal fluid and causes purulent meningitis. An antecedent upper respiratory infection may be a contributing factor.
• The meningococci after getting attached, gets endocytosed by parasite directed endocytosis across epithelium.
• The alteration in the gene expression induce a specific structural change which causes endocytosis.
• Meningococci once it enters the circulation survives and multiplies in it causing systemic circulation.

• Major damage is induced by host immune mechanisms.
• N. meningitidis has blebs of endotoxin rich vesicles which are released into the blood stream which activitates host immune response.
• Endotoxin binding protein binds and alters the conformation of endotoxin enabling it to bind it to macrophages.
• CD14 in the endothelial cells act as receptors for endotoxin and activates macrophages which trigers an intense inflammatory response through the release of tumor necrosis factor alpha, interleukin 1beta, IL-6, IL-8, IL-10, GM-CSF and interferon gamma.
• The more number of cytokines involved greater the severity of the disease.
• Endotoxin and the complements activate the neutrophils which release inflammatory proteins through respiratory burst and degrade the tissue.

• The inflammatory process induced by meningococcal pathogen alters vascular permeability.
• Proteinuria, hypovolemia and nephrotic syndrome are results of this event.
• Pulmonary edema and respiratory failure are consequence of increased vascular permeability.

• Due to hypovolemia, intense compensatory vasoconstriction occurs which manifest as cold, pale, ischemic limbs.
• Sevre patholgical vasoconstriction causes thromobosis within the microvasculature and gangrene.
• Some patients develop vasodilation after resuscitation, yet maintain severe hypotension, acidosis and organ impairment known as warm shock.

• Most severe complication of meningococcemia is widespread purpura fulminans, thrombosis and hemorrhagic necrosis in large areas of the skin and infraction of limbs resulting in gangrene.
• Procoagulation pathways are upregulated in sepsis causing intravascular generation of thrombin.

• Acute myocardial failure may manifest as hypotension, tachycardia and shock.
• Pro inflammatory mediators can have a negative ionotropic effect depressing the myocardial function.
• Tumor necrosis factor alpha, interleukin 1beta and nitric oxide have a negative ionotropic effect.
• Electrolyte imbalance also plays a vital role in cardiac dysfunction.

The above pictures shows the hands and feet affected by gangrene in meningococcemia.

• Impaired renal perfusion causes elevated urea and creatinine levels.
• Vasomotor nephropathy and acute tubularr necrosis occurs in severe cases.

• Neutrophil adhesion, coagulation activation and platelet activation causes microvacular obstruction resulting in pulmonary function impairment.
• It may manifest as tachypnea in early stages.
• Pulmonary edema and respiratory failure are the late complications of the sepsis.

• Impaired blood flow causes dysfunction of gastrointestinal tract.
• Prolonged ileus can cuase ischemic ulceration and perforation.

• Direct invasion of meninges by bacteria causes meningitis.
• Organ underperfusion causes signs and symptoms of shock.
• Raised intracranial tension may cause cerebral hernation.
• Direct bacterial activity, indirect inflammatory mediator activity and cerebral edema causes neurological damage.

• The toll like receptor system (TLR) protects the body from invasive pathogens and also causes destruction of host in fulminent infections.
• The cell wall of Neisseria meningitidis has molecules that activate the TLR system in a dose dependent manner. This causes the release inflammatory mediators which can cause organ dysfunction and meningococcemia.
• The lipopolysacchrides in the outer membrane is another factor that illicits immune response.
• Peptidoglycan, bacterial lipoprotein and genetic polymorphism are factors that help contribute to broaden the inflammatory response.
• There is a close association between the load of meningococci, (alive or dead in CSF), plasma and magnitude of inflammatory response to the patient.

• Neisseria secretes IgA1 protease which splits IgA1 at the hinge region.^[3]

Meningococci after entering the systemic circulaion get seeded to different parts of the body mainly meninges and skin. Sites like eyes, joints, pericardiucan also be seeded by the organism. When the breeding bacteria reaches a threshold it produces systemic symptoms like musche ache, fever and malaise. The TLR4 and TLR2 from the preoptic area of anterior hypothalamus are expressed which produces the fever causing cytokines like interleukin 1 and interleukin 6 and tumor necrosis factor alpha. They activate the cycloxygenase system which produces prostaglandin E2 and activates the hypothalamic prostaglandin E2 and the hypothalamic thermoregulation center raises the body temperature, increases muscle work and alter skin perfusion.

• Meningococcal lipopolysachride in plasma
• Meningococcal lipopolysacchride in CSF.
• Meningococcal DNA copies.

Patients who were diagnosed to have massive disseminated intravascular coagulation or disseminated septic shock had almost 1000 fold higher amount of LPS in plasma and CSF and copies of DNA of meningococcus than those with only meningitis with the same incubation period.

• Meningococcal meningitis presents as headache, fever, nuchal rigidity. Kernig sign will be present.
• A hemorrhagic skin rash is usually found which is less than 10 mm in diameter.
• As the organism grows in the blood stream, it transverse blood brain barrier and invade subarachnoid space.
• There they multiply and produce the signs and symptoms of meningitis.
• Approximately 50 % of the patients will have a positive blood cultures.

The endothelial cells and Kupffer cells forms a complex receptor system that helps to remove the whole bacteria, lipopolysacchrides (LPS) and DNA molecules.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Meningococcemia is caused by a bacteria called Neisseria meningitidis. The bacteria frequently lives in a person’s upper respiratory tract without causing visible signs of illness. The bacteria can be spread from person to person through respiratory droplets, patients may get infected if they are around someone with the condition when they sneeze or cough. Family members and those closely exposed to someone with the condition are at increased risk. The infection occurs more frequently in winter and early spring.

• N. meningitidis is a gram negative bacteria.
• It belongs to phylum proteobacterium from the family of Neisseriaceae.
• It belongs to class beta proteobacterium.
• The order is Neisseriales.
• It belongs to family Neisseriaceae.
• Genus name is Neisseria.
• Species name is N. meningitidis.

• N. meningitidis are gram-negative, coffee-bean shaped diplococci that may occur intracellularly or extracellularly in PMN leukocytes.^[1]
• N. meningitidis is a fastidious organism, which grows best at 35-37°C with ~5% CO2 (or in a candle-jar).
• It can grow on both a blood agar plate (BAP) and a chocolate agar plate (CAP).
• Colonies of N. meningitidis are grey and unpigmented on a BAP and appear round, smooth, moist, glistening, and convex, with a clearly defined edge. N. meningitidis appear as large, colorless-to-grey, opaque colonies on a CAP.
• Prior to identification and characterization testing procedures, isolates should always be inspected for purity of growth and a single colony should be re-streaked, when necessary, to obtain a pure culture
• Twelve serogroups, based on the biochemical composition of capsular polysaccharides, are currently recognized: A, B, C, H, I, K, L, W135, X, Y, Z, and 29E (Z’).
• Serogroup D is no longer recognized as a serogroup.
• Serogroups A, B, C, W135 and Y are the 5 most common causes of bacterial meningitis.
• Serogroup A has been the most common cause of epidemics in Africa and Asia.
• Serogroups C, W135, and X have also been reported as causes of epidemics in several parts of Africa as well. Serogroup-specific antisera for these major serogroups are available commercially.

• MC58 (serogroup B), Z2491(serogroup A), FAM18 (serogroup C) have been identified.
• 70% of the genome is core meningococcal genome that accounts for major metbolic process.
• IHT-A1 locus contains genes for synthesising capsule, and transport of it.

• Virulence is determined by capsular polysacchride, outer membrane proteins and lipopolysacchride.
• The epidemics are due to modified expression of this capsule.
• Meningococci that cannot be grouped are usually found in nasopharynx of the contacts.
• Endotoxin is a major component of the outer membrane.^[2]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: João André Alves Silva, M.D. [2]; Alejandro Lemor, M.D. [3]

Meningococcemia must be differentiated from other diseases that cause neurological symptoms, such as brain abscess, encephalitis, delirium tremens, brain tumor, and subarachnoid hemorrhage. The rash component of meningococcemia must be differentiated from other illnesses causing skin rash, such as chickenpox, herpes zoster, erythema multiforme, among others.

• Brain abscess – Brain abscess is a focal infection of the brain parenchyma commonly caused by bacteria, fungal and parasitic pathogens. Imaging and neurosurgical aspiration is required for differentiation in addition to CSF profile.

• Encephalitis – Encephalitis is the inflammation of brain. Meningitis can itself cause encephalitis and is called meningoencephalitis. The symptoms appear gradually in encephalitis but occur abruptly in meningitis.

• Delirium tremens – Delirium tremens and alcohol withdrawal should be differentiated from meningitis especially when present with confusion and fever. Both the conditions can coexist.

• Brain tumor – Brain tumors can simulate purulent meningitis with symptoms of fever, signs of meningeal irritation and marked CSF pleocytosis. Irritation of leptomeninges by tumor and its breakdown products causes these symptoms.^[1] Determination of creatine kinase BB and carcinoembryonic antigenhelps in differentiating.^[2]

• Subarachnoid hemorrhage – Subarachnoid hemorrhage also presents with severe headache, neck stiffness, nausea and vomiting like meningitis. It is a medical emergency. Imaging studies help in differentiation. Tubercular meningitis should be considered in the differential diagnosis in cases of nonaneurysmal subarachnoid hemorrhage.^[3]

Different rash-like conditions may be misdiagnosed with meningococcemia, including:^[4]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Cafer Zorkun, M.D., Ph.D. [2], Ammu Susheela, M.D. [3]

Meningococcus occurs through out the year, however the incidence is highest in late winter and early spring. It is the second most common community acquired bacterial infections. The highest incidence worldwide is in a place called sub Saharan Africa called meningitis belt. Children are mostly affected by this disease.

• Case rate was 1-2 per 100,000 in the US in 1980. More recently, there are approximately 2,500 cases of meningococcal infections per year in the United States.
• Since the introduction of Haemophilus influenzae type b vaccine in 1990 for infants the majority of cases of bacterial meningitis have been in adults; historically 45-87% of cases have been in children.
• Humans are the only natural reservoir of meningococcus. As many as 10% of adolescents and adults are asymptomatic transient carriers of N. meningitidis, most strains of which are not pathogenic (i.e., strains that are not categorized)
• Meningococcal disease occurs throughout the year, however, the incidence is highest in the late winter and early spring.
• The communicability of N. meningitidis is generally limited. In studies of households in which a case of meningococcal disease has occurred, only 3%–4% of households had secondary cases. Most households had only one secondary case. Estimates of the risk of secondary transmission are generally 2–4 cases per 1,000 household members at risk. However, this risk is 500–800 times that in the general population.
• Second most common cause of community-acquired adult bacterial meningitis after pneumococcus.
• In West African countries during 1996-1997 there were 213,658 cases and 21,830 deaths due to menigococcal disease.
• Fewer than 1000 cases annually in the United States. Higher rates of disease occur in other countries. The largest burden is in sub-Saharan Africa, where epidemics during the dry season can cause disease in up to 2% of a population, resulting in thousands of cases and deaths during large epidemics.
• Incidence rates of N. meningitidis are generally highest in children less than five years of age and in adolescents.
• N. meningitidis can also cause a severe bacteremia, called meningococcemia.
• The worldwide distribution of serogroups of N. meningitidis is variable.
• In the Americas, Europe, and Australia, serogroups B and C are the most common, while serogroup A causes the majority of disease in Africa and Asia ^[2].
• Sometimes serogroups can emerge, increasing in importance in a specific country or region, like serogroup C in China (20) or serogroup Y in North America^[3][4].
• Worldwide, the incidence of meningitis due to N. meningitidis is highest in a region of sub-Saharan African known as the “meningitis belt” .
• This hyper-endemic region extends from Senegal to Ethiopia, and is characterized by seasonal epidemics during the dry season (incidence rate: 10-100 cases per 100,000 population), punctuated by explosive epidemics in 8-12 year cycles (incidence rates can be greater than 1,000 cases per 100,000 population).
• Across the meningitis belt, at least 350 million people are at risk for meningitis during these annual epidemics. Meningitis epidemics are generally caused by serogroup A, although outbreaks have also been caused by serogroups C, W135, and X.
• Outbreaks of different serogroups may overlap, therefore, laboratory confirmation is important both to recognize and monitor the progression of outbreaks.

• Prior to 2000, an estimated 1,400 to 2,800 cases of meningococcal disease occurred each year in the United States, a rate of 0.5 to 1.1 per 100,000 population.
• The proportion of meningococcal cases caused by serogroup Y increased from 2% during 1989 through 1991 to 37% during 1997 through 2002.
• Serogroups B, C, and Y are the major causes of meningococcal disease in the United States, each being responsible for approximately one third of cases.
• Among infants younger than 1 year of age, more than 50% of cases are caused by serogroup B, for which no vaccine is licensed or available in the United States.
• Of all cases of meningococcal disease among persons 11 years of age or older, 75% are caused by serogroups C, Y, or W-135.
• Meningococcal disease incidence has decreased since 2000, and incidence of serogroups C and Y, which represent the majority of cases of vaccine-preventable meningococcal disease, are at historic lows.
• A peak in disease incidence among persons 18 to 21 years of age has persisted, even after routine vaccination of adolescents was recommended in 2005.
• From 2000–2004 to 2005–2009, the estimated annual number of cases of serogroups C and Y meningococcal disease decreased 74% among persons aged 11 through 14 years but only 27% among persons aged 15 through 18 years.

Race Number Rate¶ White 42 0.13 Black 16 0.21 Other 4 0.12 Total 62 0.14 ¶ Cases per 100,000 population Table adapted from CDC Surveillance for ABCs Report: Neisseria meningitidis, 2013 – Provisional [5] Syndrome Cases Death¶ Meningitis 31 4 Bacteremia without focus 13 3 ¶ Deaths per 100,000 cases with known outcome Table adapted from CDC Surveillance for ABCs Report: Neisseria meningitidis, 2013 – Provisional [5]

Adolescents and young adults 16 through 21 years of age have higher rates of meningococcal disease. The following are statistics regarding college aged students and the rate of meningococcus infection:

• Rates of meningococcus in US college students as a whole 0.7 per 100,000.
• Rates of meningococcus in US persons aged 18-23 not in college 1.5 per 100,000.
• Rates of freshmen living in dormitories 4.6 per 100,000.
• Rates for college students in UK 13.2 per 100,000 versus those not in college of 5.5 per 100,000.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Cafer Zorkun, M.D., Ph.D. [2], Ammu Susheela, M.D. [3]

Risk factors of meningococcemia include age group of infants or old age, closed communities, seasons of winter and early spring, complement deficiency, asplenia and travel to endemic regions especially sub-Saharan African meningitis belt.

• Certain groups of people are at increased risk for meningococcal disease.
• Episodic epidemic nature of meningococcal meningitis particularly among young children and military recruits was known since the 18th century.
• Epidemics occur generally among poorest groups where crowding and lack of sanitation are common.
• The bacteria can be spread from person to person through respiratory droplets.
• Family members and those closely exposed to someone with the condition are at increased risk.
• The infection occurs more frequently in winter and early spring.
• For some of these groups, there are recommended vaccines that prevent two of the three major serogroups (“strains”) of Neisseria meningitidis bacteria that cause most illness in the United States

• Adolescents and young adults 16 through 21 years of age have higher rates of meningococcal disease.
• Infants are also at higher risk for meningococcal disease.
• More than 50% of meningococcal disease in children 0-6 months is caused by serogroup B; serogroup Y is also more prevalent in this age group.

• There are certain diseases, medications and surgical procedures that may weaken the immune system and increase risk ofmeningococcal disease like the following conditions.

• Complement component deficiency
• Functional or anatomic asplenia (no spleen).

• College students, especially first-year college students living in residence halls, are at a slightly increased risk for meningococcal disease compared with other persons of the same age.
• Closed communities such as prisons have a high incidence of meningococcal infections

• Travelers to the meningitis belt in sub-Saharan Africa may be at risk for meningococcal disease, particularly during the dry season.

• Several conditions have been associated with development of epidemics in meningococcal belt.
• They include the following.

• Medical conditions: Immunological susceptibility of the population.
• Demographic conditions: Travel and large population displacements.
• Socioeconomic conditions: Poor living conditions and overcrowded housing.
• Climatic conditions: Drought and dust storms.^[1]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Ammu Susheela, M.D. [2]

Routine screening is not recommended for meningococcemia.

• Routine antimicrobial susceptibility testing of meningococcal isolates is not currently recommended.
• Surveillance of susceptibility patterns in populations should be conducted in order to monitor trends in N. meningitidis susceptibility.
• State and local health departments should notify the Centers for Disease Control and Prevention (CDC) if resistance to ciprofloxacin or other agents used for treatment or prophylaxis is detected.
• Passive and active surveillance systems are used to monitor meningococcal disease, which is a reportable disease in the United States. Through a national passive reporting system, state health departments collect and transmit weekly reports of cases to CDC through the National Electronic Telecommunications System for Surveillance (NETSS).
• The goals of meningococcal surveillance are:

• To detect outbreaks of meningococcal disease so that appropriate control measures can be promptly instituted, and
• To assess changes in the epidemiology of meningococcal disease over time to permit the most efficient allocation of resources and formulation of the most effective disease control and prevention policies.

• Meningococcal serogroup surveillance data are important to monitor the impact of quadrivalent meningococcal conjugate vaccine.
• Meningococcal serogroup data also help to determine the epidemiologic link between cases in cluster or outbreak situations.^[1]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Cafer Zorkun, M.D., Ph.D. [2]; Ammu Susheela, M.D. [3]

Neisseria meningitidis bacteria can cause meningitis to fatal septicemia. The symptoms of meningitis appear within 3-7 days of exposure and presents with fever and signs of bacterial meningitis. If it causes septicemia, it can be very fatal where the patient dies in few hours. In non fatal conditions they develop disabilities like arthritis, gangrene, disseminated intravascular coagulopathy and cutaneous vasculitis. The outcome is uncertain in septicemic patients but prognosis is good in non septicemic patients with early intervention and treatment.

• A common outcome of meningococcal infection is meningitis. When caused by Neisseria meningitidis bacteria it is known as meningococcal meningitis. When someone has meningococcal meningitis, the protective membranes covering their brain and spinal cord, known as the meninges, become infected and swell.
• The symptoms of meningococcal meningitis can appear quickly or over several days. Typically they develop within 3-7 days after exposure.
• In newborns and infants, the classic symptoms of fever, headache, and neck stiffness may be absent or difficult to notice. The infant may appear to be slow or inactive, irritable, vomiting or feeding poorly. In young children, doctors may also look at the child’s reflexes, which can also be a sign of meningitis.
• In adults the symptoms are mainly fever, headache, stiff neck, nausea, vomiting, photophobia and altered mental status.
• Meningococcal meningitis is very serious and can be fatal. In fatal cases, deaths can occur in as little as a few hours. In non-fatal cases, permanent disabilities can include hearing loss and brain damage.

• Blood stream infection of Neisseria meningitidis bacteria can cause either either septicemia or bacteremia.
• The bacteria enter the bloodstream and multiply, damaging the walls of the blood vessels and causing bleeding into the skin and organs.
• Clinical manifestations include fatigue, vomiting, cold hands and feet, chills, severe aches, pain in the muscles, joints, chest or abdomen, rapid breathing and diarrhea.
• In the later stages patients develop a dark purple rash.
• Meningococcal septicemia is very serious and can be fatal.
• In fatal cases, death can occur within few hours.
• In non-fatal cases, permanent disabilities can include amputation of toes, fingers, or limbs or severe scarring as a result of skin grafts.

Patients who do not develop meningitis also tend to have a poorer outcome.

• Arthritis
• Disseminated intravascular coagulopathy (DIC)
• Gangrene due to lack of blood supply, that may lead to limb amputation.
• Inflammation of blood vessels in the skin (cutaneous vasculitis).
• Myocarditis
• Pericarditis
• Shock
• Severe damage to adrenal glands that can lead to low blood pressure (Waterhouse-Friderichsen syndrome).

• 10%-15% of cases are fatal. Of patients who recover 11%-19% have permanent hearing loss, mental retardation, loss of limbs, or other serious sequelae.

• Early treatment results in a good outcome. When shock develops, the outcome is less certain.
• Individuals with the following conditions may have a life threatening outcome:

• Disseminated intravascular coagulopathy (DIC) – a severe bleeding disorder
• Kidney failure
• Shock^[1]