Meningococcemia

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Practice Essentials

Meningococcemia is a bloodstream infection (BSI) caused by Neisseria meningitidis. Its wide variety of acute presentations result from its ability to produce diffuse endovascular damage.

Chronic meningococcemia is an infrequent presentation with skin and joint findings, without any meningeal involvement.[1]

The most commonly affected age groups are 6 months-5 years and 15-24 years.



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A 9-month-old baby in septic shock with purpuric Neisseria meningitis skin lesions. Photo by D. Scott Smith, MD, taken at Stanford University Hospital....

Signs and symptoms

Patients with acute meningococcemia may present with meningitis, meningitis with meningococcemia, or meningococcemia without apparent meningitis.

The clinical presentation of meningococcemia may include any of the following[1] :



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Scattered petechiae in a patient with acute meningococcemia.

In fulminant meningococcemia, a hemorrhagic eruption, hypotension, cardiac depression, and rapid enlargement of petechiae and purpuric lesions may be seen.



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Child with severe meningococcal disease and purpura fulminans.

Serogroup W disease may be associated with atypical presentations, including septic arthritis, pneumonia, endocarditis, and epiglottitis.

The meningitis of meningococcemia is associated with the following[1, 2] :

Meningococcemia is characterized by the following[1] :

The physical findings may include the following[1] :

See Clinical Presentation for more detail.

Diagnosis

The laboratory findings in the early stages of meningococcal disease often are nonspecific. A definitive diagnosis requires retrieval of meningococci from blood, cerebrospinal fluid, joint fluid, or skin lesions. Studies may include the following[1] :

See Workup for more detail.

Management

Clinical guideline summaries related to meningococcal disease include the following:

Patients with a rash consistent with meningococcemia should be started on parenteral antibiotics within 1 hour of presentation.[5]

Conditions associated with poor outcomes include the following[1] :

Antibiotics recommended for the treatment of meningococcemia include the following[6] :

See Treatment and Medication for more detail.

Background

N meningitidis is an encapsulated gram-negative diplococcus. There are at least 12 serogroups of the bacterium based on capsular polysaccharide antigenic differences. Serogroups A, B, C, Y, and W-135 cause 90% of human disease.

See Pathophysiology, Etiology, and Workup for more detail.

Humans are the only reservoir of N meningitidis, which is transiently part of the oropharyngeal flora of up to 10% of the population. These individuals remain asymptomatic. N meningitidis is transmitted by respiratory secretions or by close contact, which facilitates the exchange of secretions. The incubation period ranges from 2-10 days. Epidemics most commonly are due to A, B, or C serotypes.

Risk groups include the following[4, 7] :

Specific categories of individuals at high risk for meningococcal disease include the following[8] :

Thirty percent to 50% of cases of acute meningococcemia present with meningitis alone, 40% with meningitis and BSI, and 7-10% with BSI alone.[9]

See Presentation and Workup for more detail.

N meningitides remains a major infectious cause of childhood death in developed countries. The mortality rate remains around 5-10%. There has been little improvement in morbidity and mortality since the beginning of the antibiotic era because of the inability of antimicrobials to prevent the cardiovascular collapse brought about by the organism’s endotoxin.[10]



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Dorsum of the hand showing petechiae. Courtesy of Professor Chien Liu.

Carriers

Approximately 2% of children younger than 2 years, 5% of children up to 17 years, and 20-40% of young adults are carriers of N meningitidis. Overcrowded conditions (eg, schools, military camps) can significantly increase the carrier rate. 

Screening of military recruits performed during recent epidemics demonstrated that, although as many as 95% of recruits were oropharyngeal carriers, only 1% developed systemic disease. Because very few of those infected had ever been in contact with another patient with a similar history, asymptomatic carriage is thought to be the major source of transmission of pathogenic strains.

Immunity to N meningitidis appears to be acquired through the intermittent nasal carriage of meningococci and by antigenic cross-reaction with enteric flora during the first 2 decades of life.

See Pathophysiology, Etiology, and Epidemiology for more details.

Pathophysiology

Meningococcemia results in widespread vascular injury characterized by endothelial necrosis, intraluminal thrombosis, and perivascular hemorrhage. Endotoxin, cytokines, and free radicals damage the vascular endothelium, producing platelet deposition and vasculitis. Cytokines play a major role in its pathogenesis by causing severe hypotension, reduced cardiac output, and increased endothelial permeability.[11]

The clinical picture of meningococcemia is the product of compartmental intravascular infection and intracranial bacterial growth and inflammation. The pathogen binds tightly to the endothelial cells by type IV pili. From this arises microcolonies on the apical portion of the endothelial cell.[12] These bacteria invade the subarachnoid space with resultant meningitis in 50-70% of cases. In a study of 862 patients, 37-49% developed meningitis without shock, 10-18% developed shock without meningitis, 7-12% developed both, and 10-18% with mild meningococcemia developed neither meningitis nor shock.[13]

Multiple organ failure, shock, and death may ensue as a result of anoxia in vital organs and massive disseminated intravascular coagulation (DIC).

Patients with fulminant meningococcemia develop thrombosis and hemorrhage in the skin, the mucous membranes, the serosal surfaces, the adrenal sinusoids, and the renal glomeruli. Adrenal hemorrhage may occur and rarely may be extensive enough to lead to adrenal necrosis (Waterhouse-Friderichsen syndrome).

The Sanarelli-Shwartzman phenomenon has provided valuable insights into the complex relationship between coagulation, inflammation, and the immune response in septic shock. This newfound understanding has the potential to pave the way for improved treatments for sepsis and other inflammatory conditions. Studying the Shwartzman-like reaction in animal models can offer further insights into the pathophysiology of sepsis, potentially benefiting critically ill patients who have experienced various physiological insults. Additionally, exploring the dermal Shwartzman reaction may aid in understanding rare cases of purpura fulminans triggered by uncommon bacterial infections.[14]

Despite challenges and errors in scientific inquiry, advancements in technology are driving accelerated discovery in understanding the human host response to infection. It is critical to learn from past mistakes and adhere to ethical standards in biomedical research to ensure patient safety and well-being. Moreover, thrombosis of glomerular capillaries in the Shwartzman reaction may lead to renal cortical necrosis, a key feature of the disseminated intravascular coagulation (DIC) model.

Similar thrombi containing numerous leukocytes may be found in the lungs and myocardium.

Primary meningococcal septic arthritis has been described.[15]

Virulence factors

Meningococci have 3 important virulence factors, as follows[16] :

A polysaccharide capsule (which also determines the serogroup) enables the organism to resist phagocytosis.[11]

An LOS can be shed in large amounts by a process called blebbing, causing fever, shock, and other pathophysiology. This is considered the principal factor that produces the high endotoxin levels in meningococcal sepsis. Meningococcal LOS interacts with human cells, producing proinflammatory cytokines and chemokines, including interleukin 1 (IL-1), IL-6, and tumor necrosis factor (TNF). LOS is one of the important structures that mediate meningococcal attachment to and invasion into epithelial cells.[17]

LOS triggers the innate immune system by activating the Toll-like receptor 4MD2 cell surface receptor complex and myeloid in non-myeloid human sounds. The degree of activation of complement then coagulation system is directly related to the bacterial load.[18]

IgA1 protease cleaves lysosomal membrane glycoprotein-1 (LAMP1), helping the organism to survive intracellularly.

Septicemia

The clinical syndrome results from the activation and continued stimulation of the immune system by proinflammatory cytokines. This process is directly caused by bacterial components, such as endotoxins released from the bacterial cell wall, and is indirectly caused by the activation of inflammatory cells. The clinical spectrum of meningococcal septicemia is produced by 4 basic processes (ie, capillary leak, coagulopathy, metabolic derangement, and myocardial failure). Combined, the processes produce multiorgan failure that usually causes cardiorespiratory depression and, possibly, renal, neurologic, and gastrointestinal (GI) failure.[19]

Capillary leak

From presentation until 2-4 days after illness onset, vascular permeability massively increases. Albumin and other plasma proteins leak into the intravascular space and urine, causing severe hypovolemia. This initially is compensated for by homeostatic mechanisms, including vasoconstriction. However, progression of the leak results in decreased venous return to the heart and a significantly reduced cardiac output.

Hypovolemia that is resistant to volume replacement is associated with increased mortality due to meningococcal sepsis. Children with severe disease often require fluid resuscitation involving volumes several times their blood volume in the first 24 hours of the illness, mostly in the first few hours. Pulmonary edema is common and occurs after 40-60 mL/kg of fluid has been given; it is treated with artificial ventilation.

Although capillary leak is the most important clinical event, the underlying pathophysiology is unclear. Some evidence suggests that meningococci and neutrophils cause the loss of negatively charged glycosaminoglycans, which are normally present on the endothelium. Also, the repulsive effect of albumin may be reduced in meningococcal infection; this change allows the protein leak. Albumin is normally confined to the vasculature because of its large size and negative charge, which repels the endothelial negative charge.

Coagulopathy

In meningococcemia, a severe bleeding tendency often is simultaneously present with severe thrombosis in the microvasculature of the skin, often in a glove-and-stocking distribution that can necessitate amputation of digits or limbs. Clinicians face a dilemma because supplying platelets, coagulation factors, and fibrinogen may worsen the process. Meningococcal infection affects the main pathways of coagulation.

Endothelial injury results in platelet-release reactions. Along with stagnant circulation due to local vasoconstriction, platelet plugs form to start the process of intravascular thrombosis. In the plasma, soluble coagulation factors are consumed, and the natural inhibitors of coagulation (eg, the tissue factor pathway inhibitor antithrombin III) are down-regulated; this process further encourages thrombosis.

The protein C pathway probably plays a key role in the pathogenesis of purpura fulminans. A very similar rash occurs in neonates with congenital protein C deficiency and in older children who develop antibodies to protein S following varicella infection. Many patients with meningococcal infection are unable to activate protein C in the microvasculature due to endothelial downregulation of thrombomodulin.[20] Protein C and S levels are low in children with meningococcal disease. However, low levels may occur in patients with septic shock without purpura fulminans. Plasma anticoagulants (tissue factor pathway inhibitor and antithrombin) also are down-regulated in meningococcal sepsis.

The fibrinolytic system in meningococcal disease is down-regulated as well, reducing plasmin generation and removing an aspect of endogenous negative feedback to clot formation. In addition, plasminogen activator inhibitor levels are dramatically increased, further reducing the efficacy of the endogenous tissue plasminogen activator.

Metabolic derangement

Severe electrolyte abnormalities, including hypokalemia, hypocalcemia, hypomagnesemia, and hypophosphatemia, may occur in the setting of severe acidosis.

Myocardial failure

Myocardial function remains impaired even after circulating blood volume is restored and metabolic abnormalities are corrected. Reduced ejection fractions and elevated plasma troponin I levels indicate myocardial damage. A gallop rhythm often is audible, with elevated central venous pressure and hepatomegaly. Hemodynamic studies in patients with meningococcal sepsis have shown that the severity of disease is related to the degree of myocardial dysfunction.

Myocardial failure in meningococcal sepsis is undoubtedly multifactorial, but various proinflammatory mediators (eg, nitric oxide, TNF-alpha, IL-1B) released in sepsis appear to have a direct negative inotropic effect on the heart, depressing myocardial function. A study using new microarray technology showed that IL-6 is the key factor that causes myocardial depression in meningococcemia.[21, 22]

It recently has been demonstrated that meningococcal infection leads to human coronary microvascular thrombosis, vasculitis, and vascular leakage.[23]

Other factors that reduce myocardial function, such as acidosis, hypoxia, hypoglycemia, and electrolyte disturbances, all are common in severe meningococcal disease.

Meningitis

Meningococcal meningitis generally has a better prognosis than septicemia. After bacteria enter the meninges, they multiply in the CSF and pia arachnoid. In the early stages of infection, the tight junctions between the endothelial cells that form the blood-brain barrier isolate the CSF from the immune system; this isolation allows bacterial multiplication. Eventually, inflammatory cells enter the CSF and release cytokines that play a central role in the pathophysiology of meningeal inflammation.[2, 19]

Neurologic damage is a consequence of the following 3 main processes:

Cerebral edema may be caused by increased secretion of CSF, diminished reabsorption of CSF, and/or breakdown of the blood-brain barrier. Obstructive hydrocephalus may cause increased accumulation of CSF between cells.

Increased ICP secondary to cerebral edema, loss of cerebrovascular autoregulation, and reduced arterial perfusion pressure secondary to shock reduce cerebral blood flow in bacterial meningitis. Reduced cerebral blood flow with vasculitis and thrombosis of cerebral vessels may cause ischemia and neuronal injury.

Etiology

N meningitidis is a gram-negative diplococcus that grows well on blood or chocolate agar supplemented or on selective media, such as Martin-Lewis or Thayer Martin blood and incubated in a moist atmosphere enriched with carbon dioxide.



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Gram-negative intracellular diplococci. Courtesy Professor Chien Liu.

Oxidase and catalase are biochemical markers for preliminary identification of N meningitidis. Sugar fermentations are required for final identification of the species. N meningitidis ferments glucose and maltose but not sucrose or lactose.

Agglutination reactions with immune serum are used to segregate meningococci into 13 serogroups: A, B, C, D, X, Y, Z, E, W-135, H, I, K, and L, depending on the group-specific capsular polysaccharide antigen. Ninety-eight percent of infections are caused by encapsulated serogroups A, B, C, Y, and W-135, although of these groups, A, B, and C most frequently occur in meningococcal disease. The cell wall of pathogenic meningococci contains a toxic lipopolysaccharide or endotoxin that is chemically identical to enteric bacilli endotoxin.

Transmission

The human nasopharynx is the only known reservoir for N meningitidis. At any given time, up to 10% of the population may be asymptomatic, nasopharyngeal carriers. In China, the weighted carriage rate between 2005-2022 was 2.86% varying between provinces from 0 to 15.5%.[118]  

The organism is transmitted via aerosols and nasopharyngeal secretions. Attachment to the nasopharyngeal epithelial cells is aided by meningococci-expressed pili, such as the type IV pilus encoded by pilC, which binds to human cell surface protein CD46.

Meningococci may enter the bloodstream and spread to specific sites, such as the meninges or joints, or disseminate throughout the body. Five percent of individuals become long-term carriers, most of whom are asymptomatic. In outbreaks, the carriage rate of an epidemic strain can reach 90%. The likelihood of acquiring infection is increased 100 to 1000 times in intimate contacts of individuals with meningococcemia.

A study of 14,000 teenagers in the United Kingdom found that attendance at pubs or clubs, intimate kissing, and cigarette smoking each were independently and strongly associated with an increased risk of meningococcal carriage.[24]

Immunity

Passively transferred maternal antibody provides temporary protection to infants for the first 3 to 6 months of life. As the child grows older, asymptomatic exposure to a variety of encapsulated and nonencapsulated N meningitidis strains increases protective bacterial immunity. Most individuals acquire immunity to meningococcal disease by age 20 years; protective IgM and IgG are found in up to 95% of young adults.

An episode of meningococcal disease confers group-specific immunity, but a second episode may be caused by another meningococcal serogroup.

Susceptibility

Complement deficiency

A genetic component to host susceptibility to meningococcemia is becoming more established. IgG antibodies that have specificity for meningococcal polysaccharides mediate bactericidal activity. Complement is needed for the expression of this activity. Terminal complement deficiency is well known to predispose individuals to meningococcemia. Recurrent meningococcemia can occur.[25]

Genetic variants of mannose-binding lectin, a plasma opsonin that initiates another pathway of complement activation, may account for nearly one third of the cases of invasive meningococcal disease.

Meningococcemia is particularly common among individuals with deficiencies of terminal complement components C5-C9 or properdin. These late complement components are required for the bacteriolysis of meningococci.

An estimated 50-60% of individuals with late complement component deficiencies develop at least 1 episode of meningococcal disease. Many of these patients experience multiple episodes of infection.

Acquired complement deficiencies that occur in association with systemic lupus erythematosus, multiple myeloma, severe liver disease, enteropathies, and nephrotic syndrome also predispose to meningococcal infection.

Interleukin abnormalities

Specific genetic polymorphisms likely predispose individuals to mortality in severe sepsis. An association has been described between increased risk for mortality in children with meningococcal disease and polymorphisms in the IL-1 cluster.

An innate anti-inflammatory cytokine profile (low level of TNF and high level of IL-10) also is associated with fatal meningococcal disease.

Coagulation pathway abnormalities

Polymorphisms in the genes that control the coagulation pathways are being evaluated. Patients with the prothrombotic factor V Leiden mutation are at higher risk for thrombotic complications, such as amputations and skin grafting, but do not have increased mortality in meningococcemia.

Other

An increased type-1 plasminogen activator inhibitor response to TNF meningococcal septicemia has been demonstrated to result from a polymorphism in the PAI-1 gene.

Another study reported that a toll-like receptor 4 variant genotype was associated with increased mortality in children with invasive meningococcal disease.[26]

Risk factors

Most patients with meningococcal disease are previously healthy; however, patients with certain medical conditions are at increased risk of developing a meningococcal infection.

Risk factors include the following:

Patients with anatomic (splenectomy) or functional asplenia also are at increased risk for invasive meningococcal disease.

Particularly severe cases have occurred during eculizumab therapy.[29]

Epidemiology

Occurrence in the United States

The epidemiological data since 2021 has revealed a concerning surge in cases of meningococcal disease in the United States, surpassing levels seen prior to the COVID-19 pandemic. The most recent statistics from 2023 indicate a total of 422 confirmed and probable cases reported, representing the highest number recorded since 2014. This resurgence primarily is attributed to the N meningitidis serogroup Y.

Of particular note is the disproportionate impact of this uptick on specific population subsets, including individuals aged between 30 and 60 years, Black or African-American individuals, and adults living with HIV. Understanding and addressing the factors contributing to these heightened disease rates in these vulnerable populations is crucial for implementing targeted prevention and intervention strategies to mitigate the impact of meningococcal disease on public health. Further research and surveillance efforts are warranted to monitor disease trends and inform effective public health responses to safeguard the well-being of at-risk individuals.[30]

A systematic review of meningococcal carriage rates in the Americas highlighted the United States as having the second-highest rate of 24% between 2001 and 2018.[31] The increased risk of invasive meningococcal disease among young adults in high-stress, close-quarter environments, such as military recruits and college freshmen, is well-recognized. Outbreaks in these populations have prompted vaccine development efforts.[32]

Specific populations, including college freshmen, men who have sex with men (MSM), and individuals with HIV, have experienced a disproportionate burden of meningococcal infections, particularly from serogroup C. The HAART era has shown an increased relative risk of meningococcal disease among individuals with HIV, especially those with lower CD4 counts. Healthcare workers and laboratory personnel face a potential risk of acquiring meningococcal infection without proper protective measures.

Meningococcal disease cases are caused by various serogroups, with outbreaks of serogroup B infections on college campuses following the availability of the quadrivalent conjugated meningococcal vaccine.[33] Patients with complement deficiencies are at higher risk of meningococcal disease caused by serotypes Y and W-135, emphasizing the importance of targeted strategies for at-risk individuals.[34] Understanding these epidemiological trends and risk factors is crucial for guiding public health interventions and improving outcomes in populations vulnerable to meningococcal disease.[35, 36]

International occurrence

The meningitis belt in sub-Saharan Africa has a well-documented history of experiencing major epidemics of meningococcal disease at intervals ranging from 5 to 12 years, with attack rates peaking at 1,000 cases per 100,000 population during these outbreaks. While the precise risk factors for meningococcal disease epidemics in Africa remain incompletely understood, certain environmental and demographic characteristics create conducive conditions for the spread of the disease.[37]

Factors such as dry and dusty conditions prevalent during the dry season (December to June) in the region, along with the immunological susceptibility of the population, contribute to the increased vulnerability to meningococcal disease outbreaks. Additionally, factors like travel, population displacements, and crowded living conditions further exacerbate the risk of rapid transmission and escalation of meningococcal disease within communities in the sub-Saharan African region. Understanding these environmental and demographic risk factors is crucial for implementing targeted prevention and control measures to mitigate the impact of meningococcal disease epidemics in this high-risk area.[37]

Serogroups A, B, and C are responsible for the majority of meningococcal disease cases worldwide, with varying prevalence in different regions. Serogroups A and C are commonly found in Asia and Africa, while serogroups B and C are prevalent in Europe, North America, and South America.

In China, a notable decrease in meningococcal meningitis cases was observed from 1990 to 2023, with serogroup C being the predominant serogroup during this period.[38] An international outbreak of meningococcal disease associated with serogroup W-135 occurred among travelers returning from the hajj pilgrimage to Mecca in 2000 and 2001.[39]

Recent reports indicate a concerning uptick in cases involving non-vaccine serogroup X within Ghana's meningitis belt.43 This shift underscores the importance of ongoing surveillance efforts to monitor changes in serogroup distribution and inform vaccination strategies to address emerging serogroups. Understanding the evolving landscape of meningococcal disease epidemiology worldwide is crucial for effectively combating the disease and protecting at-risk populations.



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Areas with frequent epidemics of meningococcal disease. This is known as the meningitis belt of Africa; visitors to these locales may benefit from me....

Meningococcal disease also may be a significant, but underreported, problem in developing Asian countries.[40]

Europe and the United Kingdom

In Europe, invasive meningococcal disease predominantly is caused by serogroup B.

Based on data from 2017-2018, serogroup B remains the most important cause of invasive meningococcal disease in England (54%; 404/755), followed by serogroup W disease (26%), serogroup Y disease (12%), and serogroup C disease (8%).[41]

Climate-related demographics

Meningococcal infections in the United States and Northern Europe are most common in the winter, whereas cases of meningococcal disease in the African meningitis belt increase at the end of the dry season.

Race- and sex-related demographics

Mortality rates may be significantly higher in Blacks than in Whites and Asians.[42]

Meningococcal disease is somewhat more prevalent in males (1.2 cases per 100,000) than in females (1 case per 100,000).

Age-related demographics

In epidemics of meningococcal disease, people of any age may be affected, with the case distribution shifted toward older individuals.[43]

Endemic meningococcal disease is most common in children aged 6-36 months. Children younger than 6 months are protected by maternal antibodies (although occult meningococcemia, an uncommon form of infection, affects children aged 3-24 months). It is rare in neonates, but the incidence in that age group is not known.[44]



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Lesions caused by Neisseria meningitis bacteremia on the palm of the hand of a 9-month-old infant. Photo by D. Scott Smith, MD, taken at Stanford Univ....

A second, less dramatic peak in incidence occurs among teenagers and college students; this may be due to changes in social behavior and increases in close interpersonal contact in these populations. About one third of meningococcal disease cases occur in adults.

In New York City from 1989-2000, the overall incidence rates of meningococcal disease decreased. The median age of patients with meningococcal disease increased from 15 years in 1989-1991 to 30 years in 1998-2000.[45]

Prognosis

Meningococcal disease can progress very quickly and can result in loss of life, neurologic impairment, or peripheral gangrene. Patients with terminal complement component deficiency have a more favorable prognosis. A fatal outcome is highly associated with properdin deficiencies. Coagulopathy with a partial thromboplastin time of greater than 50 seconds or a fibrinogen concentration of less than 150 µg/dL also are markers of poor prognosis.

A multicenter study published in 2006 evaluated the serogroups in children with N meningitidis infection. The researchers found that meningococcal disease continues to result in substantial morbidity and mortality in children. Overall, 55 (44%) of isolates were serogroup B, 32 (26%) were serogroup C, and 27 (22%) were serogroup Y. All but 1 of the isolates (intermediate) were susceptible to penicillin. The overall mortality rate in this pediatric population was 8%.[46]

Cases of meningococcal meningitis without coma or focal neurological deficits have markedly better outcomes. Most of these patients recover completely when appropriate antimicrobial therapy is administered promptly upon presentation.

Isolated meningococcal meningitis (5% mortality rate) has a better prognosis than meningococcal septicemia (10-40% mortality rate).

Patients with higher bacterial loads on polymerase chain reaction (PCR) testing are more likely to die or have permanent disease sequelae and experience longer hospital stays.[47]

Morbidity

Complications of meningococcal infection include the following:

Complications of meningococcemia may occur at the time of acute disease or during the recovery phase. Patients with fulminant meningococcemia may develop respiratory insufficiency and require mechanical ventilation. Those with severe DIC may bleed into their lungs, urinary tract, and gastrointestinal tract. Ischemic complications of DIC have been reported in up to 50% of survivors of fulminant meningococcemia.

Complications of meningococcal infection include immune complex disease leading to arthritis, pericarditis, myocarditis, and pneumonitis 10-14 days after the primary infection. Up to 5% of patients with meningococcemia develop a nonpurulent pericarditis with substernal chest pain and dyspnea approximately 1 week after the onset of illness. Involvement of the pericardium in meningococcal disease is a well-recognized, but rare, complication. It has been described with N meningitidis serotypes C, B, W-135, and Y.[50]

Meningococcal meningitis may progress to mental obtundation, stupor, or coma, which may be related to increased ICP, and such patients are prone to herniation. Other rare complications of meningitis include acute and delayed venous thrombosis, which usually manifests as a focal neurologic deficit.

Meningococcal infection may spread through the bloodstream and localize in other parts of the body, where it can cause suppurative complications. Septic arthritis, purulent pericarditis,[51] and endophthalmitis[52] can occur but are uncommon.

Meningococcal pneumonia has been described and probably results from aspiration of N meningitidis. The W-135, Y, and B serogroups of meningococci are more likely to cause this form of meningococcal disease, as well as pericarditis and septic arthritis.[53]

Approximately 10% of patients with meningococcal disease develop nonsuppurative arthritis, usually of the knee joints. The nonsuppurative arthritis of meningococcal disease may result from tenosynovitis due to meningococcemia or a postinfectious immunologic process.

Recurrent meningococcal disease has been associated with hereditary deficiencies of various terminal components of the complement system.

Myocarditis is a complication with a high mortality risk. The frequency may be more common than is clinically recognized.[54]

Sequelae

A case-control study examined outcomes in patients who had survived meningococcal disease in adolescence and found that they had poorer mental health, social support, quality of life, and educational outcomes, as well as greater fatigue, than did well-matched control individuals.[55]

A European study found that approximately 4% of survivors of meningococcal infection had sequelae. In the United Kingdom, approximately 5% of survivors have neurologic sequelae, mainly sensorineural deafness. Amputation or skin grafting due to digital or limb ischemia and severe skin necrosis is required in 2-5% of survivors in the United Kingdom.

In the United States in 2005, 11-19% of survivors of meningococcal infection had serious health sequelae, including sensorineural hearing loss, amputations, and cognitive impairment.

 

Patient Education

 

 

History

Individuals with meningococcal disease may present with a nonspecific prodrome of cough, headache, and sore throat.[1] After a few days of upper respiratory symptoms, the temperature rises abruptly, often after a chill. Malaise, weakness, myalgias, headache, nausea, vomiting, and arthralgias are common presenting symptoms. The skin rash of meningococcemia may advance from a few ill-defined lesions to a widespread petechial eruption within a few hours. In fulminant meningococcemia, a hemorrhagic eruption, hypotension, and cardiac depression, as well as rapid enlargement of petechiae and purpuric lesions, may be apparent within hours of the initial presentation. 



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Purpura in a young adult with fulminant meningococcemia.

Meningitis

Meningitis is associated with the following[2] :

In adults, bacterial meningitis has a characteristic clinical pattern, although the progression of symptoms varies somewhat.[1] Symptoms of meningitis may accompany the petechiae of meningococcemia and may produce the predominant features on presentation.

Bacterial meningitis is a febrile illness of short duration; the major symptoms include headache and a stiff neck. Lethargy or drowsiness are common. Confusion, agitated delirium, and stupor are rarer; however, coma is an ominous prognostic sign.

The clinical pattern of bacterial meningitis often is atypical in young children because headache and nuchal rigidity frequently are absent.[1] Irritability, especially upon movement, is a common presenting manifestation of meningitis in a young child. Convulsions may signal the onset of meningitis at this age. Progression of the illness results in the development of lassitude and a more constant fever, often accompanied by abdominal discomfort. Projectile vomiting may occur.

Septicemia

Septicemia may be confused with influenza, particularly when myalgia is prominent. Meningococcal septicemia is characterized by the following[56] :

Symptoms of meningitis and septicemia may occur together and may complicate the distinction between an acute decreased level of consciousness due to hypotension and that caused by elevated ICP.

Chronic meningococcemia

Chronic meningococcemia is an intermittent bacteremic illness that lasts from at least 1 week to as long as several months. The fever tends to be intermittent, with afebrile periods ranging from 2-10 days, during which the patient seems completely healthy. As the disease progresses, the febrile periods become more common, and the fever may become continuous.[58]  It may present with joint symptoms.[59]  Cutaneous manifestations are variable and can consist of rose-colored macules and papules, indurated nodules, petechiae, purpura, or large hemorrhagic areas. Chronic meningococcemia may mimic the dermatitis-arthritis syndrome of subacute gonococcemia. 

Patients may recover spontaneously or progress to systemic complications such as meningitis. The prognosis for treated patients is excellent, with a cure rate of nearly 100% with appropriate antibiotic therapy. Penicillin G at 6-12 million U/day in divided doses for a minimum of 7 days is effective therapy.

 

Physical Examination

Patients are severely ill.[1] Tachycardia and mild hypotension are present. Patients with acute meningococcemia usually present with moderate fever (average, 39.5°C). High fever (average, 40.6°C) is present in fulminant meningococcemia.

Rapidly developing signs and symptoms of congestive heart failure, hypotension, pulmonary edema, and respiratory failure may be present and mark the progression to fulminant meningococcemia. Laboratory or imaging evidence of end-organ damage such as pericarditis often appear concurrently.

Dermatologic manifestations

Petechiae develop in 50-80% of patients with meningococcal disease and involve the axillae, flanks, wrists, and ankles, although they can progress to any part of the body. Lesions commonly begin on the trunk and legs in areas where pressure is applied.



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Dorsum of the hand showing petechiae. Courtesy of Professor Chien Liu.



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Petechiae on lower extremities. Courtesy of Professor Chien Liu.



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Scattered petechiae in a patient with acute meningococcemia.



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The legs of a 22-year-old woman in septic shock with a rapidly evolving purpuric rash. Photo by D. Scott Smith, MD, taken at Stanford University Hospi....

Petechiae often are located in the center of lighter-colored macules. They are discrete lesions 1-2mm in diameter. Confluence of lesions results in hemorrhagic patches, often with central necrosis. In some cases, a transient maculopapular rash develops, usually lasting for less than 48 hours. Rash may be missed early in an individual with dark skin.[60]

Critically ill patients with sepsis may develop rapidly progressing petechiae, ecchymoses, and extensive, palpable purpura or retiform purpura, accompanied by DIC and vascular collapse.

Skin lesions tend to occur in crops on any part of the body, occasionally presenting on the conjunctivae and the mucous membranes (see the first image below). The face usually is spared, and involvement of the palms and the soles is less common (see the second image below).



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Conjunctival petechiae. Courtesy of Professor Chien Liu.



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Petechiae on the palm. Courtesy of Professor Chien Liu.

Fulminant meningococcemia

Fulminant meningococcemia is associated with a purpuric eruption, as shown in the image below.[1] Lesions generally are characterized by maplike purpuric or necrotic areas.

Hemorrhages may appear on the buccal mucosa and the conjunctivae. Less frequently, fulminant meningococcemia presents as purpura fulminans. In rare cases, no skin lesions develop. Symmetrical, peripheral gangrene has been described in this form. Amputation may be required in severe cases of necrosis.



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Child with severe meningococcal disease and purpura fulminans.

Signs of meningitis

The characteristic physical examination findings of meningitis include pain and resistance to neck flexion.[1] Other signs of meningeal irritation also can be elicited. Children with meningitis may have none of these findings.

The Kernig sign is positive when the leg cannot be extended more than 135° on the thigh when flexed 90° at the hip. The Brudzinski sign is positive when neck flexion causes involuntary flexion of the thighs and the legs.

Focal neurologic signs are uncommon presenting findings of bacterial meningitis. However, nuchal rigidity may not be elicited in patients who are comatose and who may have signs of focal or diffuse neurologic deficits.

Papilledema is not a presenting feature of bacterial meningitis and suggests the presence of an accompanying process.

Approach Considerations

Definitive diagnosis of meningococcal infection requires culture of meningococci from blood, spinal fluid, joint fluid, or, occasionally, from skin lesions.[1]

The laboratory findings in the early stages of meningococcal disease are nonspecific and often unremarkable. For example, patients with fulminant meningococcemia may present with a normal white blood cell (WBC) count or leukopenia.

A study of adults with fulminant meningococcemia found that the following 4 variables at the time of admission portend a fatal outcome:

Blood culture

Cultures in meningococcal infection produce transparent, nonpigmented colonies that are oxidase positive and nonhemolytic. Overall, the sensitivity of blood culture is 50-60% in untreated patients.[62]

In meningococcemia, organisms have been isolated by blood culture in almost 100% of patients. The results are not available for 12-24 hours.

Obtain blood cultures before administering antibiotics. These can be drawn in rapid succession so as not to delay the institution of appropriate antibiotics.

Throat culture

A throat culture should be obtained; however, the diagnosis of meningococcemia cannot be made solely from a positive result from throat culture, because asymptomatic colonization is not uncommon.[1]

Complement deficiencies should be sought for complicated infections and recurrent or familial disease.

Diagnosis of chronic meningococcemia

The diagnosis of chronic meningococcemia is confirmed with the identification of Neisseria meningitidis from blood cultures. Multiple (3-6 sets) blood cultures are necessary to confirm BSI because of the high rate of false-negative test results. This may be due to recent use of oral antibiotics that were given before the seriousness of the patient's clinical state was recognized. Alternatively, a novel N meningitidis–specific polymerase chain reaction assay performed on skin biopsy specimens may prove to be helpful for this diagnostic challenge.[63]

Chronic meningococcemia significantly differs histopathologically from acute meningococcemia. The patient is not in shock /thrombi do not occlude the capillaries orvenules, and endothelial swelling does not occur. The most common finding in a person with chronic meningococcemia is a leukocytoclastic angiitis.

Imaging studies

Chest radiography is useful to evaluate for pneumonia and acute respiratory distress syndrome. Echocardiography can be used to evaluate for myocardial dysfunction and pericarditis. Deep muscle and bone involvement can be evaluated with magnetic resonance imaging (MRI).

Hematologic Studies

Collect blood cultures (2 sets, with at least 10 mL per bottle) in any febrile patient with petechiae.[1, 6] A complete blood count (CBC), platelet count, blood urea nitrogen (BUN) study, and creatinine clearance evaluation, as well as a series of coagulation studies, can be used to evaluate a consumptive coagulopathy. 

Gram stain of the peripheral blood buffy coat may reveal gram-negative diplococci in fulminant meningococcemia.

Rapid latex antigen tests may assist with diagnosis. The latex agglutination test has 50-100% sensitivity and high specificity. However, it has a high rate of false-negative results.

Coagulation tests

DIC is a laboratory diagnosis, but no single laboratory test is diagnostic.[1, 6] Instead, DIC is recognized clinically by a pattern of changes in numerous coagulation tests. Typically, these changes include lowered platelet count, prolonged prothrombin time, prolonged partial thromboplastin time, lowered fibrinogen levels, and the presence of fibrin-split products in the circulation. Not all of these changes are found in all patients. Fibrinogen, an acute-phase reactant, may be elevated in patients with DIC.

White blood cell count

In patients with meningococcal infections, the WBC count and C-reactive protein level may be elevated at presentation or may increase during the subsequent 24 hours. However, these values are not reliable markers of infection.

In a study of 128 consecutive children with meningococcal sepsis who were admitted to a pediatric intensive care unit, only 14% had a WBC count of more than 20 X 109/L, and 71% had a WBC count of less than 15 X 109/L.

A low WBC count is a poor prognostic finding and should raise concerns about rapid disease progression.

Metabolic abnormalities

Biochemical disturbance is common in children who have shock with or without impaired renal function. The following abnormalities frequently occur:

Other

Evaluate for evidence of end-organ damage (eg, kidney or hepatic failure) with appropriate blood tests.

Needle Aspirates and Skin Biopsy

Gram-negative diplococci may be observed in punch biopsy and needle aspiration specimens of skin lesions or buffy coat preparations.[6] Gram-negative diplococci also may be recovered from joint fluid. Findings on Gram stains of skin lesions remain positive for up to 2 days after the start of antibiotics and form a rapid means of diagnosis, including when meningitis is not present and when spinal fluid culture findings are negative, owing to the administration of antibiotics. 



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Gram-negative intracellular diplococci. Courtesy Professor Chien Liu.

In one study, needle aspirates or skin biopsy specimens from patients with meningococcal sepsis tested using Gram stain yielded a 72% sensitivity; in another study, sensitivity was reportedly 80% using scraped material from petechiae.[64] However, a later prospective, controlled study combining Gram stain and culture of skin biopsy specimens, reported a sensitivity of 56%.[65]

Histology

Leukocytoclastic vasculitis, thrombosis, and organisms often are demonstrated in biopsy specimens collected from patients with acute meningococcemia.[6]

Cutaneous petechiae and purpura correspond to thrombi in the dermal vessels composed of neutrophils, platelets, and fibrin. Acute vasculitis with neutrophils and nuclear "dust" is present within and around vessels. This process leads to hemorrhage into the surrounding tissue. Meningococci often can be seen in the luminal thrombi and vessel walls. Intraepidermal and subepidermal neutrophilic pustules also may be present.

Perivascular lymphocytic infiltrate with few neutrophils characterize chronic meningococcemia, although leukocytoclastic vasculitis may be seen in biopsies of petechiae.

Serogrouping-Serotyping

Meningococcal polymerase chain reaction assay

Meningococcal PCR is a rapid method for diagnosing CSF infection.[1, 66] PCR of spinal fluid has a sensitivity and specificity of more than 90% in the diagnosis of meningococcal meningitis; it is useful when antibiotics have been administered and can be used to rapidly type strains in developing epidemics. Diagnosis and serogrouping of N meningitidis infection also can be performed on formalin-fixed tissue samples using immunohistochemical analysis and PCR.[1]

Researchers conducted a meta-analysis of nine studies involving 4533 cerebrospinal fluid (CSF) samples to evaluate the diagnostic accuracy of antigen tests for N meningitidis. Using polymerase chain reaction (PCR) as the reference standard, the analysis found a pooled sensitivity of 91.2% and a pooled specificity of 93.8%. Specifically, the MeningoSpeed test showed a sensitivity of 93.4% and a specificity of 91.9%. When testing for N meningitidis serogroup X, the sensitivity was 92.4% and the specificity was 99.2%. The results indicate that antigen tests are highly sensitive and specific for diagnosing meningococcal meningitis in CSF samples, making them useful for identifying suspected N meningitidis infections.[67]

Slide agglutination test

With serogrouping, polysaccharide antigens on the capsule are identified by a slide agglutination test using polyclonal antibodies.

Enzyme-linked immunosorbent assay

With serotyping and serosubtyping, outer membrane proteins (PorB and PorA) can be identified by an enzyme-linked immunosorbent assay (ELISA) using monoclonal antibodies.

Lumbar Puncture

Brain imaging studies before a lumbar puncture (LP) are unnecessary unless the patient is obtunded, has focal neurologic signs, has experienced a seizure within the previous week, or presents with papilledema.

Perform LP for CSF evaluation. Immediately stain and culture the spinal fluid. (CSF culture yields a sensitivity of up to 70% in untreated patients.)

Gram stain of the CSF should be performed immediately and examined microscopically. Organisms can be observed in the CSF in approximately half of patients who present with meningococcal meningitis. (Gram stain can have a higher yield than blood cultures.)

Send the CSF for a WBC count, a WBC differential, total protein content, and glucose studies. Send additional tests as indicated for ruling out other diagnoses.

Bacterial meningitis produces various inflammatory changes in the CSF. The CSF becomes turbid with more than 1000 WBC/µL, and the cells predominantly are predominantly polymorphonuclear. The intracranial pressure (ICP) may be elevated. The total protein content is increased, and the glucose level, which is normally 60% of the simultaneous blood glucose level, becomes lowered (hypoglycorrhachia).

Detection of N meningitidis capsular polysaccharide antigen in CSF and urine with rapid serologic tests based on latex particle agglutination is commercially available.

Contraindications for lumbar puncture

In the presence of purpura or petechiae, LP may be hazardous and may add few data to aid in the diagnosis. In a patient with a depressed level of consciousness, shock, or any of the features listed below, lumbar puncture can be delayed, and treatment can immediately begin.

The following are contraindications to lumber puncture (unless increased intracranial pressure [ICP] is ruled out):

Approach Considerations

As mortality may be reduced with early antibiotic therapy, patients with a meningococcal rash should receive parenteral antibiotics by means of an intravenous (IV) or intramuscular (IM) route as soon as the diagnosis is suspected.[6, 68]  The IM administration of medications should be avoided in cases with shock because decreased tissue perfusion severely limits their delivery to the infected sites.

Other than antimicrobial treatment, supportive measures in meningococcal disease may be required to correct circulatory collapse. Severe adrenal insufficiency requires corticosteroid replacement.[56]

Chemoprophylaxis for meningococcal infection should be administered to intimate household, daycare center, and nursery school contacts of cases. Vaccinate household and other intimate contacts.

Although increasingly well recognized and managed in children, meningococcal disease often is not diagnosed and treated in adults in medical settings. Fluid resuscitation may not be sufficiently aggressive, early intubation often is not considered, and the rapidity of disease progression in an adult often is not understood.

Treatment of complications

Arthritis has been found in about 10% of patients with meningococcal disease. This complication usually occurs within the first few days of treatment and manifests as an effusion of a large joint, often the knee. Occasionally, repeated arthrocentesis is needed to control symptoms.

Other possible complications include ischemic conditions caused by coagulation abnormalities and neurologic complications of meningitis. The patient must be observed for any neurologic sequelae; the frequency of neurologic abnormalities seems to be related to the severity of the acute disease. Some neurologic sequelae can develop in the absence of meningitis.

Inpatient care

Hospitalization usually is required for all patients even if only adequately monitor their response to antibiotic and other therapies.[1, 6] Promptly begin antibiotic treatment. Respiratory precautions generally include placement of the patient in a private room with proper air handling and the use of a respiratory mask by any person entering the patient's room. Discontinue respiratory isolation precautions after 24 hours of antibiotics.

Monitor blood pressure, urine output, and cardiac function, as well as platelets, fibrin, and fibrin degradation products.

Transfer to a PICU is necessary in approximately 20% of pediatric cases of meningococcal infection.

Guidelines

Several clinical guideline summaries related to meningococcal disease are available, as follows:

Emergency Management of Meningococcal Infection

Although many meningococcal infections rapidly improve when treated with antibiotics, meningococcal disease may quickly progress.[1, 6] The time from the appearance of the first symptoms to death may be only a few hours.

Because the mortality rate of meningococcal disease maybe as high as 40%, all patients with fever and petechiae warrant rapid initial assessment and empiric and ongoing assessment. 

The following findings may help in the identification of severely ill patients whose condition may deteriorate and who are likely to need intensive care:

Managing shock

After basic life support and antibiotics are administered, the next priority is treating shock/hypotension with initial volume replacement at a rate of 20mL/kg.[6] A satisfactory response to volume replacement is a reduction in heart rate and improved peripheral perfusion. The patient's condition may stabilize with only volume replacement, but the patient requires close monitoring and reassessment to detect further signs of shock or pulmonary edema (due to capillary leak syndrome). 

Managing raised intracranial pressure

Suspect increased ICP if the patient has a decreased level of consciousness; focal neurologic signs; unequal, dilated, or poorly reacting pupils; abnormal posturing or seizures; relative hypertension or bradycardia; or if the patient is agitated or combative. Because papilledema is a late sign of increased ICP, its absence early on does not justify the discontinuance of monitoring for its development.

After initiating basic life support measures and administering antibiotics, the therapeutic goal is to maintain oxygen and nutrient delivery to the brain. For this reason, shock must be corrected in individuals with both shock and increased ICP to maintain cerebral perfusion pressure. After correcting shock/hypotension with volume replacement and inotropic support as necessary, cautiously manage the fluid balance to avoid further increasing the ICP.

Performance of a lumbar puncture should always be avoided

Treatment of patients with limited shock and no increased ICP

Reassess patients with limited shock and no increased ICP, as well as patients who respond rapidly to minimal volume replacement, for signs of deterioration during the first 48 hours following admission.

The use of corticosteroids in meningitis may be considered. Several studies revealed that adjunctive dexamethasone reduces sensorineural hearing loss (but not mortality or other neurologic sequelae) in children and infants with H influenzae type B meningitis. Few adverse effects occur with dexamethasone administration. No reports of delayed CSF sterilization or treatment failure are known. A meta-analysis of findings from randomized, controlled trials suggested that such treatment has a benefit in preventing sequelae in meningococcal meningitis and pneumococcal meningitis in childhood.

Data are limited for meningococcal meningitis, and the pathophysiologic events are likely to be similar to those of other forms of bacterial meningitis. In some animal models, anti-inflammatory therapy was beneficial. No evidence of the benefits of steroid use in patients with septic shock is known, and steroid use is necessary only with meningitis.

If hypoadrenalism is suspected because of resistance to large doses of inotropic drugs, administer adrenal replacement doses of hydrocortisone.

Replacement corticosteroids should not be used routinely in pediatric sepsis; their use is controversial in adult sepsis.[70, 71]

Pharmacologic Therapy

The most important measure in treating meningococcemia is early detection and rapid administration of antibiotics.[1, 6] Third-generation cephalosporins such as ceftriaxone or cefotaxime are preferred because of their effectiveness and ease of administration.

Meningococci are resistant to vancomycin, polymyxin, or achievable serum levels of aminoglycoside antibiotics.

Empiric therapy

Empiric antibiotic therapy should provide coverage of likely meningeal pathogens when no rash is present, when the etiology of meningitis is uncertain, and when an immediate microbiologic diagnosis is unavailable. This therapy can be narrowed down to specific therapy when the specific pathogen and its antibiotic sensitivities are determined.

A third-generation cephalosporin is the appropriate antibiotic until culture results are available. Although meningococcal infection is the most common bacterial cause of a petechial or purpuric rash and meningitis, other organisms (including H influenzae type B and Streptococcus pneumoniae) can cause shock and a nonblanching rash.

H influenzae type B is an uncommon cause of meningitis in developed countries with comprehensive vaccination programs. Most cases of bacterial meningitis that occur outside of the United States are due to Neisseria meningitides, with the rest resulting from S pneumoniae. In the United States, S pneumoniae is predominant.

Empiric antibiotic therapy for meningitis based on age is as follows:

Chloramphenicol 100 mg/kg/day in 4 divided doses (up to 4 g/day maximum dose) can be given as an alternative. Because there may be increased mortality compared with other regimens, it is no longer recommended as a first-line treatment.[72]

Dexamethasone is indicated in the treatment of known or suspected pneumococcal meningitis in adults and children with H influenzae type B meningitis. Although of no benefit in meningococcal meningitis, it can be given until the causative organism is identified.[72]

Surgical Treatment of Ischemic Complications

Patients who survive the initial acute phase of fulminant meningococcemia are at increased risk for serious complications due to extensive tissue necrosis.

Early in the course of tissue injury, conservative therapy is recommended until a distinct line of demarcation is apparent between viable and nonviable tissue. Once the patient is stable, débridement of all necrotic tissue is essential and may necessitate extensive removal of skin, subcutaneous tissue, and muscle. Large defects may be covered using microvascular free flaps or skin grafts. The use of artificial skin can spare the patient immediate use of autograft sites, which frequently are limited.[73] Avoid early limb amputation, because significant tissue recovery may occur as the disease progresses.

Poor tissue perfusion also may lead to dental complications that require extensive extraction of severely affected teeth.

Anecdotally, fasciotomy may preserve limb and digit function in severe meningococcal septicemia when impending peripheral gangrene and increased compartment pressures are present. Measure compartment pressures and assess peripheral pulses with Doppler ultrasonography when patients have impaired limb perfusion or severe edema.

Monitoring and Follow-Up

Pericarditis can occur during the recuperative period. It may present with fever and shortness of breath upon minimal exertion.

Late skeletal deformities are rare, but epiphyseal avascular necrosis and epiphyseal-metaphyseal defects have been described. These usually occur in the lower extremities and result in angular deformity and inequality of leg length.

Observe patients for any late neurologic sequelae. Abnormal findings on electroencephalography or cerebral computed tomography (CT) scanning, as well as epileptogenic activity, sensorineural hearing loss, impaired vestibular function, and neuropsychological impairment, have been found in up to 30% of survivors 1 year after an episode of meningococcal disease. The frequency of serious neurologic sequelae in individuals who survive an episode is 3%.

Follow-up care at least 6 weeks after meningococcal infection should include the following:

Vaccine

High-risk individuals

Specific categories of individuals at high risk for meningococcal disease include the following[4, 7, 8] :

Vaccination recommendations

The Advisory Committee on Immunization Practices (ACIP) in the United States recommends MenACWY vaccination for adolescents aged 11 or 12 years, with a booster dose at age 16 years.[4]  It also is recommended for individuals aged 2 months and older who are at increased risk, including those with certain medical conditions, microbiologists exposed to the bacteria, persons in outbreak settings, travelers to high-risk areas, unvaccinated college students, and military recruits. Booster doses are advised for those who remain at risk.

ACIP recommends MenB vaccination for individuals aged 10 years and older who are at increased risk, with boosters 1 year after completing the primary series, then every 2-3 years.[4] It also is recommended for microbiologists, individuals in outbreak settings, and adolescents aged 16-23 through shared clinical decision-making. The preferred age for MenB vaccination is 16-18. Booster doses are not recommended unless the individual becomes at increased risk. Booster doses are recommended for previously vaccinated individuals at continued risk.

Recommended meningococcal vaccines and administration schedules for children and adults by the Advisory Committee on Immunization Practices are summarized in the following table. See the complete recommendations for more detail.[4]

 Recommended meningococcal vaccines and administration schedules for children and adults — Advisory Committee on Immunization Practices, United States, 2020



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Abbreviations: MenACWY-CRM = meningococcal groups A, C, W, and Y oligosaccharide diphtheria CRM197 conjugate vaccine; MenACWY-D = meningococcal groups A, C, W, and Y polysaccharide diphtheria toxoid conjugate vaccine; MenACWY-TT = meningococcal groups A, C, W, and Y polysaccharide tetanus toxoid conjugate vaccine; MenB-4C = four-component meningococcal group B vaccine; MenB-FHbp = meningococcal group B factor H binding protein vaccine.* MenB vaccines are licensed in the United States only for persons aged 10–25 years.† College freshmen living in residence halls should receive at least 1 dose of MenACWY within 5 years before college entry. The preferred timing of the most recent dose is on or after their 16th birthday. If only 1 dose of vaccine was administered before the 16th birthday, a booster dose should be administered before enrollment. Adolescents who received a first dose after their 16th birthday do not need another dose before college entry unless it has been more than 5 years since the dose. Certain schools, colleges, and universities have policies requiring vaccination against meningococcal disease as a condition of enrollment.§ When given to healthy adolescents who are not otherwise at increased risk for meningococcal disease, 2 doses of MenB-FHbp should be administered at 0 and 6 months. For persons at increased risk for meningococcal disease and for use during serogroup B meningococcal disease outbreaks, 3 doses of MenB-FHbp should be administered at 0, 1–2, and 6 months to provide earlier protection and maximize short-term immunogenicity.

A 5-in-1 meningococcal ABCWY vaccine became available in 2023.[76]  A second vaccine is under FDA review[77]

Prevention of Secondary Cases

Antimicrobial chemoprophylaxis of close contacts is the primary means of preventing secondary cases of sporadic meningococcal disease.[6] Person-to-person transmission can be interrupted by administration of an antimicrobial that eradicates the asymptomatic nasopharyngeal carrier state. Sulfonamides, rifampin, minocycline, ciprofloxacin, and ceftriaxone are the drugs that have been shown to eradicate meningococci from the nasopharynx.

Because the rate of disease in secondary contacts is highest immediately after the onset of the disease in the patient, chemoprophylaxis should be administered as soon as possible, preferably within 24 hours. If chemoprophylaxis is delayed by more than 14 days, it probably is of limited value.

Populations at Risk for Secondary Cases

Meningococcal infection probably is introduced into families by asymptomatic adults and then spread through 1 or more household contacts to infect younger family members. Household contacts are defined as individuals who live in the same home with a person who has a meningococcal disease. An operational definition commonly used by public health authorities includes persons eating and sleeping under the same roof as the index case.

The attack rate of meningococcal disease among household contacts has been estimated to be several hundred times greater than that in the general population. The secondary attack rate is inversely proportional to age and is estimated at approximately 10% in household contacts aged 1-4 years. Among adults, the risk is 3-4%.

It should be assumed that the risk of acquiring meningococcal disease is significantly increased in other closed populations, such as those of daycare facilities, nursery schools, and prisons.

Healthcare workers who are exposed to aerosol secretions from patients with meningococcal disease are 25 times more likely to contract the disease compared with the general population.

The likelihood of acquiring infection is increased 100-1000 times in sexually intimate contacts of individuals with meningococcemia.

Indications for Chemoprophylaxis

The American Academy of Pediatrics recommends antimicrobial chemoprophylaxis for contacts of persons with invasive meningococcal disease, including household members, individuals at daycare centers and nursery schools, and persons directly exposed to the patient's oral secretions (eg, kissing, sharing of food or beverages) within the 7 days preceding the onset of the illness in the index case.

Cellmates should also be given chemoprophylaxis.

Antimicrobial chemoprophylaxis is required in hospital personnel who have had direct, unprotected exposure to droplets and nasopharyngeal secretions of a patient with meningococcal disease from activities such as mouth-to-mouth resuscitation, endotracheal intubation, nasotracheal suctioning or endotracheal tube management.

To further decrease infection risk in the clinical setting, staff caring for patients with known or suspected meningococcal infections should wear masks, in addition to standard precautions.

Patients with meningococcal disease who are hospitalized should be placed on respiratory precautions for the first 24 hours of effective antimicrobial therapy. When this is done, the risk for hospital personnel with casual or indirect contact is believed to be negligible. Antimicrobial chemoprophylaxis is not recommended in hospital personnel who have only casual or indirect contact with a patient with meningococcal disease.

For travelers, antimicrobial chemoprophylaxis should be considered for any passenger who had direct contact with respiratory secretions from an index patient or anyone seated directly next to an index patient on a prolonged flight (ie, one that lasts ≥8h).

 Antibiotic chemoprophylaxis is most effective if administered within 24 hours of contact.

Prophylactic Antibiotics

Rifampin

Rifampin commonly is used for meningococcal prophylaxis of household contacts in the United States; a 2-day oral course is recommended. Avoid in pregnancy.

Children younger than 1 month: 5mg /kg q12h

Children older than 1 month: 10 mg/kg q12h   

Adults: 600mg q1h 

Ciprofloxacin

Children younger than 18 years: not recommended because it has caused cartilage damage in immature experimental animals.

Adults: A single dose of ciprofloxacin (500 mg) is an effective alternative to rifampin for the eradication of meningococcal carriage in adults. 

Ceftriaxone

A single IM injection of ceftriaxone eradicates meningococcal carriage. Ceftriaxone is preferred in children who refuse oral medication and may be used in pregnancy.

Children younger than 15 years: 125 mg IM

Adults: 250 mg IM

Meningococcal disease can be prevented by vaccination with group-specific meningococcal capsular polysaccharides.[4]  Purified polysaccharides of groups A, C, Y, and W-135 meningococci have been used to stimulate group-specific humoral bactericidal antibodies.

Consultations

 Consultations in meningococcal disease include the following:

 Local department of health to be  notified of suspected and/or proven cases of meningococcal infection to assist in the evaluation and treatment of close contacts.

Complications

Survivors of meningococcal meningitis may suffer long-term complications, including the following[78] :

Guidelines Summary

Several clinical guideline summaries related to meningococcal disease are available, as follows:

Meningococcal vaccination recommendations (2020) by the Advisory Committee on Immunization Practices

Recommended meningococcal vaccines and administration schedules for children and adults by the Advisory Committee on Immunization Practices are summarized in the following table. See the complete recommendations for more detail.[4]

Recommended meningococcal vaccines and administration schedules for children and adults — Advisory Committee on Immunization Practices, United States, 2020



View Table

See Table

Abbreviations: MenACWY-CRM = meningococcal groups A, C, W, and Y oligosaccharide diphtheria CRM197 conjugate vaccine; MenACWY-D = meningococcal groups A, C, W, and Y polysaccharide diphtheria toxoid conjugate vaccine; MenACWY-TT = meningococcal groups A, C, W, and Y polysaccharide tetanus toxoid conjugate vaccine; MenB-4C = four-component meningococcal group B vaccine; MenB-FHbp = meningococcal group B factor H binding protein vaccine.* MenB vaccines are licensed in the United States only for persons aged 10–25 years.† College freshmen living in residence halls should receive at least 1 dose of MenACWY within 5 years before college entry. The preferred timing of the most recent dose is on or after their 16th birthday. If only 1 dose of vaccine was administered before the 16th birthday, a booster dose should be administered before enrollment. Adolescents who received a first dose after their 16th birthday do not need another dose before college entry unless it has been more than 5 years since the dose. Certain schools, colleges, and universities have policies requiring vaccination against meningococcal disease as a condition of enrollment.§ When given to healthy adolescents who are not otherwise at increased risk for meningococcal disease, 2 doses of MenB-FHbp should be administered at 0 and 6 months. For persons at increased risk for meningococcal disease and for use during serogroup B meningococcal disease outbreaks, 3 doses of MenB-FHbp should be administered at 0, 1–2, and 6 months to provide earlier protection and maximize short-term immunogenicity.

Medication Summary

The role of antibiotics in managing meningococcemia is to treat an active infection, provide prophylaxis to protect those with significant exposure to cases of Neisseria meningitidis and eliminate the carrier state in asymptomatic individuals.

Drugs effective in treating active meningococcal infection include 3rd generation cephalosporins like ceftriaxone and penicillin G. Meningococcal resistance to penicillins has occurred; the mechanism of resistance involves altered penicillin-binding proteins. Chloramphenicol is less effective and should be avoided if other options are available. Antimicrobial susceptibility testing should be obtained before penicillin and ampicillin use. Resistance to ceftriaxone is rare.

The duration of antimicrobial treatment is dictated by the clinical response. It should be no less than 7 days

Individuals with greater than 4 hours of close contact with an index patient during the week before the onset of illness are at an increased risk for infection. Individuals at risk include housemates, daycare contacts, cellmates, or individuals exposed to infected nasopharyngeal secretions (eg, through kissing, mouth-to-mouth resuscitation, intubation, and suctioning). 

Rifampin and ciprofloxacin commonly are used for chemoprophylaxis. Ciprofloxacin should be avoided in pregnant and lactating women. Ciprofloxacin-resistant strains have been reported, and susceptibility testing should be used to guide prophylaxis based on local prevalence.[81]  Rifampin may eradicate carriage in up to 80-90% of individuals, but resistant strains have occurred.[82] Other agents that can be used include ceftriaxone and azithromycin. A single dose of intramuscular ceftriaxone may be used in children or adults. During epidemics, vaccination should be adjunctive to antibiotic chemoprophylaxis for susceptible contacts. The eradication of carriage is also indicated in the index case unless third-generation cephalosporins have been used.

See the Treatment Section for more detail.

Chloramphenicol

Clinical Context:  Chloramphenicol can be used in patients with penicillin and cephalosporin allergies. It binds to 50S bacterial-ribosomal subunits and inhibits bacterial growth by inhibiting protein synthesis. It is effective against gram-negative and gram-positive bacteria. Chloramphenicol-resistant strains are found in Southeast Asia but are rare in the United States. It should be avoided if other options are available.

Ceftriaxone

Clinical Context:  Ceftriaxone is a third-generation cephalosporin with broad-spectrum, gram-negative activity. It has lower efficacy against gram-positive organisms. Ceftriaxone arrests bacterial growth by binding to 1 or more penicillin-binding proteins. It has successfully been used to treat pediatric meningococcal meningitis. It is useful in special circumstances (ie, relatively penicillin-resistant organisms, hypersensitivity reactions to penicillin or chloramphenicol).

Ceftriaxone is a first-line antibiotic for empiric therapy of meningitis or sepsis while culture and susceptibility data are pending. Cefotaxime or ceftriaxone are the preferred agents for the treatment of confirmed meningococcal disease.

Cefotaxime (Claforan)

Clinical Context:  Cefotaxime is a third-generation cephalosporin with a gram-negative spectrum. It has lower efficacy against gram-positive organisms. Cefotaxime has been used successfully in pediatric meningococcal meningitis

The drug is more expensive than penicillin, but most authorities believe that it is as efficacious as penicillin in the treatment of meningococcal disease.

Cefotaxime arrests bacterial cell wall synthesis, which, in turn, inhibits bacterial growth. It is used for penicillin-resistant strains.

Cefotaxime is used as a first-line antibiotic for the empiric therapy of meningitis or sepsis while culture and susceptibility data are pending. Cefotaxime or ceftriaxone are the preferred agents for the treatment of confirmed meningococcal disease.

Ampicillin

Clinical Context:  A broad-spectrum penicillin that interferes with bacterial cell-wall synthesis during active replication, causing bactericidal activity against susceptible organisms.

Rifampin (Rifadin)

Clinical Context:  Rifampin is a semisynthetic derivative of rifamycin B that inhibits bacterial and mycobacterial RNA synthesis by binding to the beta subunit of deoxyribonucleic acid (DNA)–dependent RNA polymerase, thus inhibiting binding to DNA and blocking RNA transcription.

Rifampin is commonly used for meningococcal prophylaxis of household contacts in United States, where one third of prevalent strains are sulfadiazine resistant.

Ciprofloxacin (Cipro, Cipro XR)

Clinical Context:  Ciprofloxacin is a fluoroquinolone. It inhibits bacterial DNA synthesis and, consequently, growth. A single dose of 500mg has been found to provide an effective alternative to rifampin for the eradication of meningococcal carriage in adults. Ciprofloxacin is commonly used for meningococcal prophylaxis. It is not recommended for persons younger than 18 years because it has caused cartilage damage in immature experimental animals. Resistance has been reported, and it should only be used if the strain is known to be susceptible.

Penicillin G aqueous (Crystapen, Penicillin G potassium, Penicillin G sodium)

Clinical Context:  Penicillin G interferes with synthesis of cell wall mucopeptide during active multiplication, resulting in bactericidal activity against susceptible microorganisms. It should not be used empirically, against N Meningitidis. 

Infections caused by organisms classified as relatively resistant to penicillin, based on a minimum inhibitory concentration (MIC) of 0.1-1 µg/mL of penicillin, seem to respond to this drug as well as fully susceptible organisms do.

Class Summary

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting. People who come into household contact with patients who have meningococcal disease are at risk of acquiring this illness. Person-to-person transmission can be interrupted by chemoprophylaxis, which eradicates the asymptomatic nasopharyngeal carrier state. Rifampin, ciprofloxacin and ceftriaxone are the antimicrobials used to eradicate meningococci from the nasopharynx.

Mortality in meningococcal infections may be reduced with early antibiotic therapy. Regarding community management, because mortality may be reduced with early antibiotic therapy, patients with a meningococcal rash should receive parenteral benzylpenicillin by an IV route as soon as the diagnosis is suspected. IM antibiotic injections may be less effective in a patient with shock and poor tissue perfusion. Cefotaxime, ceftriaxone, or chloramphenicol (avoid if other options available) can be considered for penicillin-allergic patients. Empiric antibiotic therapy for meningitis based on age is as follows:

- Neonates - Ampicillin and cefotaxime

- Infants aged 1-3 months - Ampicillin and cefotaxime

- Older infants, children, and adults - Cefotaxime or ceftriaxone

Meningitis group A C Y and W-135 vaccine diphtheria conjugate vaccine (Menactra, Menveo)

Clinical Context:  Diphtheria toxoid conjugate vaccine induces the production of bactericidal antibodies specific to capsular polysaccharides of serogroups A, C, Y, and W-135.

Meningococcal C and Y/haemophilus influenza type B vaccine (MenHibrix)

Clinical Context:  Contains antigenic capsular polysaccharides (ie, meningococcal serogroups A and C, Haemophilus influenzae type b) that convey active immunity by stimulating endogenous antibody production; antibodies have been associated with protection from invasive meningococcal disease.

Meningococcal Polysaccharide Vaccine A/C/Y/W-135

Clinical Context:  This is a quadrivalent vaccine for meningitis prophylaxis. It is considered an adjunct to antibiotic chemoprophylaxis.

Meningococcal group B vaccine (Bexsero, Trumenba)

Clinical Context:  Protection against invasive meningococcal disease is conferred mainly by complement-mediated antibody-dependent killing of N meningitidis.

Meningococcal ABCWY pentavalent vaccine (Penbraya)

Clinical Context: 

Class Summary

These agents may be used to prevent and control outbreaks of serogroup C meningococcal disease.

Dexamethasone (Decadron)

Clinical Context:  Dexamethasone may reduce sensorineural hearing loss in children and infants with H influenzae type B meningitis. Administer this agent to all children with suspected bacterial meningitis (the pathophysiology is likely to be similar). Dexamethasone does not reduce CNS clearance of bacteria or cause treatment failure. It is of no proven benefit in meningococcal meningitis and may be stopped following microbiologic confirmation.

Class Summary

These agents elicit anti-inflammatory and immunosuppressive properties and cause profound and varied metabolic effects. They modify the body's immune response to diverse stimuli.

What is meningococcemia?What are the signs and symptoms of acute meningococcemia?What are the signs and symptoms of meningitis in meningococcemia?What are the signs and symptoms of meningococcemia?What are the physical findings characteristic of meningococcemia?What is the role of lab testing in the diagnosis of meningococcemia?Which organizations have released treatment guidelines for meningococcemia?When should patients with a meningococcemia rash be treated?Which antibiotics are recommended in the treatment of meningococcemia?What is N meningitidis?What are the possible presentations of acute meningococcemia?What are the carrier rates for N meningitidis?What is chronic meningococcemia?What is the pathophysiology of meningococcemia?What is the clinical progression of meningococcemia?What are the manifestations of fulminant meningococcemia?What are the virulence factors associated with meningococcemia?What is the pathophysiology of septicemia in meningococcemia?What is the role of vascular permeability in the pathophysiology of meningococcemia?What is the role of coagulopathy in the pathophysiology of meningococcemia?Which metabolic derangements may occur in meningococcemia?What causes myocardial failure in patients with meningococcemia?What is the pathophysiology of meningitis in meningococcemia?What causes meningococcemia?How is meningococcemia transmitted?How is immunity against meningococcemia acquired?What is the role of terminal complement deficiency in the etiology of meningococcemia?Which genetic factors increase the risk for mortality from meningococcemia?Which risks are increased in patients with meningococcemia and the prothrombotic factor V Leiden mutation?What is the role of the PAI-1 gene in the etiology of meningococcemia?What are the risk factors for meningococcemia?What is the incidence of meningococcemia in the US?What is the global incidence of meningococcemia?What is the incidence of meningococcemia in Europe and the United Kingdom?How does climate-affect the incidence of meningococcemia?What are the racial predilections for meningococcemia?How does the prevalence of meningococcemia vary by sex?How does the incidence of meningococcemia vary by age?What is the prognosis of meningococcemia?What are possible complications of meningococcemia?What is the prevalence of immune complex disease due to meningococcal infection?What are the complications of meningococcal meningitis?What are the suppurative complications of meningococcemia?What is the prevalence of nonsuppurative arthritis in meningococcemia?What are possible complications of recurrent meningococcal disease?What are the sequelae associated with meningococcemia?What is the mortality rate for meningococcemia?What information about meningococcemia should patients receive?Which history associated with is characteristic of meningococcemia?What are the signs and symptoms of meningitis in meningococcemia?What are the signs and symptoms of septicemia in meningococcemia?Which history findings suggest chronic meningococcemia?Which physical findings are characteristic of meningococcemia?What are the dermatologic manifestations of meningococcemia?Which physical findings are characteristic of fulminant meningococcemia?Which physical findings are characteristic of meningococcal septicemia?Which physical findings are characteristic of meningitis in meningococcemia?Which conditions should be included in the cutaneous differential diagnoses of meningococcemia?Which conditions should be included in the differential diagnoses of chromic meningococcemia?How are rheumatic diseases differentiated from meningococcemia?Which conditions should be included in the differential diagnoses of meningococcemia when petechiae and fever are present?Which conditions should be included in the differential diagnoses of meningococcal infection?What is the role of lab testing in the diagnosis of meningococcemia?Which factors increase the risk for mortality in fulminant meningococcemia?What is the role of blood cultures in the workup of meningococcemia?What is the role of throat cultures in the workup of meningococcemia?How is chronic meningococcemia diagnosed?What is the role of imaging studies in the workup of meningococcemia?When is blood culture indicated in the workup of meningococcemia?What does a gram stain reveal in the workup of fulminant meningococcemia?How is a rapid latex antigen test used in the workup of meningococcemia?What is the role of coagulation tests in the workup of meningococcemia?What is the role of white blood cell count in the workup of meningococcemia?Which metabolic abnormalities may be present in meningococcemia?How is end-organ damage assessed in the workup of meningococcemia?What is the role of needle aspirations and skin biopsies in the workup of meningococcemia?Which findings of biopsy specimens are characteristic of acute meningococcemia?What are the indications of cutaneous petechiae and purpura in the histology of meningococcemia?Which histologic findings are characteristic of chronic meningococcemia?What is the role of polymerase chain reaction (PCR) assay in the workup of meningococcemia?What is the role of a slide agglutination test use in the workup of meningococcemia?What is the role of enzyme-linked immunosorbent assay (ELISA) in the workup of meningococcemia?When are brain imaging studies indicated in the workup of meningococcemia?What is the role of lumbar puncture in the workup of meningococcemia?When is a lumbar puncture contraindicated in the workup of meningococcemia?What is the initial treatment of suspected meningococcemia?What is included in the medical management septicemia and meningitis in meningococcemia?Who should receive chemoprophylaxis and vaccination against meningococcal infection?How is meningococcemia managed in adults?What are the complications of meningococcemia and how are they managed?What is included in the inpatient care for meningococcemia?Which dietary modifications are used in the treatment of meningococcemia?Which activity modifications are used in the treatment of meningococcemia?When is transfer indicated for the treatment of meningococcemia?Which organizations have published treatment guidelines for meningococcemia?What is included in the initial treatment of meningococcemia symptoms?What are the indications for intensive care in meningococcemia?What is the treatment algorithm for emergency management of meningococcemia?What is included in basic life support for meningococcemia?What are the indications of shock in meningococcemia?What is the initial therapy for shock in meningococcemia?What is the treatment of meningococcemia in patients who do not respond to initial volume replacement?When are endotracheal intubation and ventilation indicated in the treatment of meningococcemia?When should additional fluid replacement be administered in the treatment of meningococcemia?What corrections are required in the management of shock in meningococcemia?What are the indications of increased intracranial pressure (ICP) in meningococcemia?How is intracranial pressure (ICP) managed in patients with meningococcemia?What is included in the treatment of meningococcemia in patients with limited shock and no increased intracranial pressure (ICP)?What is the role of antibiotics in the treatment of meningococcemia?What is the role of cephalosporins in the treatment of meningococcemia?Which medications are ineffective in the treatment of meningococcemia?What is included in intensive supportive care for fulminant meningococcemia?What is the role of empiric therapy in the treatment of meningococcemia?Which antibiotic should be administered prior to culture results for meningococcemia?When should agents against H influenzae type B be included in empiric therapy for meningococcemia?What is the empiric antibiotic therapy for meningitis in meningococcemia?What is the role of ceftriaxone in the empiric therapy for meningococcemia?What is the role of dexamethasone in the empiric therapy for meningococcemia?What is the role of surgery in the treatment of meningococcemia?What are the signs of pericarditis in meningococcemia?Which skeletal deformities may occur in meningococcemia?What is included in monitoring for late neurologic sequelae of meningococcemia?What is included in the follow-up care of meningococcemia?How are secondary cases of sporadic meningococcal disease prevented?How is chemoprophylaxis used in the prevention of meningococcemia?What are the infection risks for secondary cases of meningococcemia?What are the American Academy of Pediatrics (AAP) recommendations for antimicrobial chemoprophylaxis to prevent secondary cases of meningococcemia?What is the role of public health authorities in the prevention of secondary meningococcemia?When is antimicrobial chemoprophylaxis against meningococcemia indicated for hospital personnel?When is antimicrobial chemoprophylaxis against meningococcemia indicated for travelers?What is the role of rifampin in the management of meningococcemia?What is the role of ciprofloxacin in the management of meningococcemia?What is the role of ceftriaxone in the management of meningococcemia?What is the role of sulfadiazine in the management of meningococcemia?How is meningococcemia prevented?Which specialist consultations are needed in the management of meningococcemia?What is the increased risk of Guillain-Barré Syndrome (GBS) from the MCV4 meningococcal vaccine?What type of vaccines are used to prevent meningococcemia?What is the effectiveness of purified polysaccharide vaccines against meningococcemia?What are the guidelines on meningococcal B vaccination by the Advisory Committee on Immunization Practices (ACIP)?What are the types of vaccines are available against meningococcemia?What are the ACIP expanded recommendations for the MenACWY-CRM vaccine to prevent meningococcemia?What is the role of serogroup B vaccines in the prevention of meningococcemia?What is the efficacy of serogroup B vaccines against meningococcemia?What is the safety of the meningococcal polysaccharide vaccine in pregnant women?What are the ACIP guidelines on meningococcal B vaccination?What is the focus of antimicrobial therapy for meningococcemia?Which drugs are effective in treating active meningococcal infection?What is the duration of antimicrobial treatment for meningococcemia?Which individuals are at increased risk for meningococcemia?How are rifampin and ciprofloxacin used in the management of meningococcemia?What is the role of chloramphenicol in the treatment of meningococcemia?Which medications in the drug class Corticosteroids are used in the treatment of Meningococcemia?Which medications in the drug class Vaccines, Inactivated, Bacterial are used in the treatment of Meningococcemia?Which medications in the drug class Antimicrobial agents are used in the treatment of Meningococcemia?

Author

Mahmud H Javid, MBBS, Consultant in Infectious Diseases, Quaid-e-Azam International Hospital, Pakistan

Disclosure: Nothing to disclose.

Coauthor(s)

Shadab Hussain Ahmed, MD, FACP, FIDSA, AAHIVS, Professor of Clinical Medicine, Renaissance School of Medicine at Stony Brook University Medical Center; Adjunct Clinical Associate Professor, Department of Medicine, New York College of Osteopathic Medicine of New York Institute of Technology; Chief, Division of Infectious Diseases, Department of Medicine, Nassau University Medical Center

Disclosure: Nothing to disclose.

Specialty Editors

Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

John L Brusch, MD, FACP, Corresponding Faculty Member, Harvard Medical School

Disclosure: Nothing to disclose.

Acknowledgements

Katrina Cathie, BM (Hons), MRCPCH, Fellow in Paediatric Clinical Research, Southampton NIHR Respiratory Biomedical Research Unit, University Hospital Southampton NHS Foundation Trust, UKKatrina Cathie, BM(Hons), MRCPCH is a member of the following medical societies: Royal College of Paediatrics and Child Health

Disclosure: Nothing to disclose.

Joanna L Chan, MD Mohs Fellow, California Skin Institute

Joanna L Chan, MD is a member of the following medical societies: American Academy of Dermatology and American Society for Dermatologic Surgery

Disclosure: Nothing to disclose.

Joseph Domachowske, MD Professor of Pediatrics, Microbiology and Immunology, Department of Pediatrics, Division of Infectious Diseases, State University of New York Upstate Medical University

Joseph Domachowske, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Society for Microbiology, Infectious Diseases Society of America, Pediatric Infectious Diseases Society, and Phi Beta Kappa

Disclosure: Nothing to disclose.

Dirk M Elston, MD Director, Ackerman Academy of Dermatopathology, New York

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Saul N Faust, MA, MBBS, PhD, MRCPCH Senior Lecturer in Pediatric Immunology and Infectious Diseases, University of Southampton; Director, Wellcome Trust Clinical Research Facility, Southampton University Hospitals NHS Trust, UK

Saul N Faust, MA, MBBS, PhD, MRCPCH is a member of the following medical societies: British Paediatric Allergy, Immunology and Infectious Group, European Society for Paediatric Infectious Diseases, International Society for Infectious Diseases, and Royal College of Paediatrics and Child Health

Disclosure: Xoma Consulting fee Consulting; GSK Honoraria Consulting; Wyeth travel and registration fee to conference investigator in study being presented at meeting; Sanofi Pasteur Consulting fee Consulting; Pfizer Consulting fee Consulting

Aaron Glatt, MD Professor of Clinical Medicine, New York Medical College; President and CEO, Former Chief Medical Officer, Departments of Medicine and Infectious Diseases, St Joseph Hospital (formerly New Island Hospital)

Aaron Glatt, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physician Executives, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Medical Association, American Society for Microbiology, American Thoracic Society, American Venereal Disease Association, Infectious Diseases Society of America, International AIDS Society, and SocietyforHealthcareEpidemiology of America

Disclosure: Nothing to disclose.

Thomas A Hoffman, MD Professor, Department of Internal Medicine, Division of Infectious Diseases, Jackson Memorial Hospital, University of Miami

Thomas A Hoffman, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Society for Microbiology, and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

David Jaimovich, MD Chief Medical Officer, Joint Commission International and Joint Commission Resources

David Jaimovich, MD is a member of the following medical societies: American Academy of Pediatrics

Disclosure: Nothing to disclose.

Michael Levin, PhD, FRCP, FRCPCH Head, Professor, Imperial College School of Medicine at St Mary's Hospital, Department of Pediatrics, London, England

Disclosure: Nothing to disclose.

Lester F Libow, MD Dermatopathologist, South Texas Dermatopathology Laboratory

Lester F Libow, MD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, and Texas Medical Association

Disclosure: Nothing to disclose.

Joseph Richard Masci, MD Professor of Medicine, Professor of Preventive Medicine, Mount Sinai School of Medicine; Director of Medicine, Elmhurst Hospital Center

Joseph Richard Masci, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, Association of Professors of Medicine, and Royal Society of Medicine

Disclosure: Nothing to disclose.

Mary D Nettleman, MD, MS, MACP Professor and Chair, Department of Medicine, Michigan State University College of Human Medicine

Mary D Nettleman, MD, MS, MACP is a member of the following medical societies: American College of Physicians, Association of Professors of Medicine, Central Society for Clinical Research, Infectious Diseases Society of America, and Society of General Internal Medicine

Disclosure: Nothing to disclose.

Gregory J Raugi, MD, PhD Professor, Department of Internal Medicine, Division of Dermatology, University of Washington at Seattle School of Medicine; Chief, Dermatology Section, Primary and Specialty Care Service, Veterans Administration Medical Center of Seattle

Gregory J Raugi, MD, PhD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Nanette Silverberg,MD Assistant Clinical Professor, Department of Dermatology, Columbia University College of Physicians and Surgeons; Director of Pediatric Dermatology, Department of Dermatology, St Luke's Roosevelt Hospital Center, Maimonides Medical Center and Beth Israel Medical Center

Nanette Silverberg is a member of the following medical societies: American Academy of Dermatology, American Academy of Pediatrics, American Association of University Women, American Medical Association, American Medical Women's Association, Dermatology Foundation, International Society of Pediatric Dermatology, Phi Beta Kappa, Sigma Xi, Society for Pediatric Dermatology, and Women's Dermatologic Society

Disclosure: Nothing to disclose.

Darvin Scott Smith, MD, MSc, DTM&H Adjunct Assistant Professor, Department of Microbiology and Immunology, Stanford University School of Medicine; Chief of Infectious Diseases and Geographic Medicine, Department of Internal Medicine, Kaiser Redwood City Hospital

Darvin Scott Smith, MD, MSc, DTM&H is a member of the following medical societies: American Medical Association, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of America, and International Society of Travel Medicine

Disclosure: Nothing to disclose.

Russell W Steele, MD Head, Division of Pediatric Infectious Diseases, Ochsner Children's Health Center; Clinical Professor, Department of Pediatrics, Tulane University School of Medicine

Russell W Steele, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Immunologists, American Pediatric Society, American Society for Microbiology, Infectious Diseases Society of America, Louisiana State Medical Society, Pediatric Infectious Diseases Society, Society for Pediatric Research, and Southern Medical Association

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Elizabeth L Tanzi, MD Co-Director, Laser Surgery, Washington Institute of Dermatologic Laser Surgery; Assistant Professor, Department of Dermatology, Johns Hopkins University School of Medicine

Elizabeth L Tanzi, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, and American Society for Laser Medicine and Surgery

Disclosure: Nothing to disclose.

Michael J Wells, MD Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine

Michael J Wells, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, and Texas Medical Association

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

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  87. Faibis S, Widmer R, Sapir S, Peretz B, Shapira J. Meningococcal septicaemia and dental complications: a literature review and two case reports. Int J Paediatr Dent. 2005 May. 15(3):213-9. [View Abstract]
  88. Aaberge IS, Oster P, Helland OS, Kristoffersen AC, Ypma E, Høiby EA, et al. Combined administration of meningococcal serogroup B outer membrane vesicle vaccine and conjugated serogroup C vaccine indicated for prevention of meningococcal disease is safe and immunogenic. Clin Diagn Lab Immunol. 2005 May. 12(5):599-605. [View Abstract]
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  90. Pollard AJ. Global epidemiology of meningococcal disease and vaccine efficacy. Pediatr Infect Dis J. 2004 Dec. 23(12 Suppl):S274-9. [View Abstract]
  91. Tucker ME. New meningococcal vaccine recommended for high-risk infants. Medscape Medical News. Jan 24, 2013. Available at http://www.medscape.com/viewarticle/778124. Accessed: Feb 5, 2013.
  92. Basta NE, Mahmoud AA, Wolfson J, Ploss A, Heller BL, Hanna S, et al. Immunogenicity of a Meningococcal B Vaccine during a University Outbreak. N Engl J Med. 2016 Jul 21. 375 (3):220-8. [View Abstract]
  93. Update: Guillain-Barre syndrome among recipients of Menactra meningococcal conjugate vaccine--United States, June 2005-September 2006. MMWR Morb Mortal Wkly Rep. 2006 Oct 20. 55(41):1120-4. [View Abstract]
  94. Martínez JV, Verbanaz SC, Jordán R, Enríquez N, Efrón ED. [Chronic meningococcemia]. Medicina (B Aires). 2008. 68 (4):298-300. [View Abstract]
  95. Buysse CM, Raat H, Hazelzet JA, Hulst JM, Cransberg K, Hop WC, et al. Long-term health status in childhood survivors of meningococcal septic shock. Arch Pediatr Adolesc Med. 2008 Nov. 162(11):1036-41. [View Abstract]
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  98. Stephens DS, Greenwood B, Brandtzaeg P. Epidemic meningitis, meningococcaemia, and Neisseria meningitidis. Lancet. 2007 Jun 30. 369(9580):2196-210. [View Abstract]
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A 9-month-old baby in septic shock with purpuric Neisseria meningitis skin lesions. Photo by D. Scott Smith, MD, taken at Stanford University Hospital.

Scattered petechiae in a patient with acute meningococcemia.

Child with severe meningococcal disease and purpura fulminans.

Dorsum of the hand showing petechiae. Courtesy of Professor Chien Liu.

Gram-negative intracellular diplococci. Courtesy Professor Chien Liu.

Areas with frequent epidemics of meningococcal disease. This is known as the meningitis belt of Africa; visitors to these locales may benefit from meningitis vaccine. Image courtesy of CDC.

Lesions caused by Neisseria meningitis bacteremia on the palm of the hand of a 9-month-old infant. Photo by D. Scott Smith, MD, taken at Stanford University Hospital.

Purpura in a young adult with fulminant meningococcemia.

Dorsum of the hand showing petechiae. Courtesy of Professor Chien Liu.

Petechiae on lower extremities. Courtesy of Professor Chien Liu.

Scattered petechiae in a patient with acute meningococcemia.

The legs of a 22-year-old woman in septic shock with a rapidly evolving purpuric rash. Photo by D. Scott Smith, MD, taken at Stanford University Hospital.

Conjunctival petechiae. Courtesy of Professor Chien Liu.

Petechiae on the palm. Courtesy of Professor Chien Liu.

Child with severe meningococcal disease and purpura fulminans.

Gram-negative intracellular diplococci. Courtesy Professor Chien Liu.

Dorsum of the hand showing petechiae. Courtesy of Professor Chien Liu.

Petechiae on the palm. Courtesy of Professor Chien Liu.

Petechiae on lower extremities. Courtesy of Professor Chien Liu.

Conjunctival petechiae. Courtesy of Professor Chien Liu.

Gram-negative intracellular diplococci. Courtesy Professor Chien Liu.

Scattered petechiae in a patient with acute meningococcemia.

Purpura in a young adult with fulminant meningococcemia.

The legs of a 22-year-old woman in septic shock with a rapidly evolving purpuric rash. Photo by D. Scott Smith, MD, taken at Stanford University Hospital.

A 9-month-old baby in septic shock with purpuric Neisseria meningitis skin lesions. Photo by D. Scott Smith, MD, taken at Stanford University Hospital.

The leg of a 9-month-old infant in septic shock with a rapidly evolving purpuric rash. Photo by D. Scott Smith, MD, taken at Stanford University Hospital.

Neisseria meningitis purpuric lesions on the ear and cheek of a 9-month-old infant who is in septic shock. Photo by D. Scott Smith, MD, taken at Stanford University Hospital.

Lesions caused by Neisseria meningitis bacteremia on the palm of the hand of a 9-month-old infant. Photo by D. Scott Smith, MD, taken at Stanford University Hospital.

Areas with frequent epidemics of meningococcal disease. This is known as the meningitis belt of Africa; visitors to these locales may benefit from meningitis vaccine. Image courtesy of CDC.

Child with severe meningococcal disease and purpura fulminans.

Flow chart shows guidelines for the emergency management of meningococcal disease in children. These guidelines may be reprinted for use in clinical areas and are available at Meningitis.org.

Flow chart shows guidelines for the emergency management of meningococcal disease in adult patients. These guidelines may be reprinted for use in clinical areas and are available from Meningitis.org.

Chart for family practice recognition and management of meningococcal disease (courtesy of Meningitis.org).

Age groupSerogroups A, C, W, and Y meningococcal conjugate vaccinesMenACWY-D (Menactra, Sanofi Pasteur) orMenACWY-CRM (Menveo, GlaxoSmithKline) orMenACWY-TT (MenQuadfi, Sanofi Pasteur)Serogroup B meningococcal vaccinesMenB-FHbp (Trumenba, Pfizer) orMenB-4C (Bexsero, GlaxoSmithKline)
2 mos–10 yrsNot routinely recommendedSee Table 3 for persons at increased riskNo recommendations for use of MenB vaccines in this population*
11–23 yrsPrimary vaccination†: 1 dose at age 11–12 yrsBooster: 1 dose at age 16 yrs if first dose administered before 16th birthdayCatch-up vaccination: Although routine vaccination is only recommended for adolescents aged 11–18 yrs, MenACWY may be administered to persons aged 19–21 yrs who have not received a dose after their 16th birthdayNote: MenACWY vaccines are interchangeablePrimary vaccination: MenB series at age 16–23 yrs on basis of shared clinical decision-making (preferred age 16–18 yrs)• MenB-FHbp§: 2 doses at 0 and 6 mos• MenB-4C: 2 doses ≥1 mo apartBooster: Not routinely recommended unless the person becomes at increased risk for meningococcal diseaseNote: MenB-FHbp and MenB-4C are not interchangeable
≥24 yrsNot routinely recommendedSee Table 3 for persons at increased riskNot routinely recommendedSee Table 3 for persons at increased risk
Age groupSerogroups A, C, W, and Y meningococcal conjugate vaccinesMenACWY-D (Menactra, Sanofi Pasteur) orMenACWY-CRM (Menveo, GlaxoSmithKline) orMenACWY-TT (MenQuadfi, Sanofi Pasteur)Serogroup B meningococcal vaccinesMenB-FHbp (Trumenba, Pfizer) orMenB-4C (Bexsero, GlaxoSmithKline)
2 mos–10 yrsNot routinely recommended                                                                     See Table 3 for persons at increased riskNo recommendations for use of MenB vaccines in this population*
11–23 yrsPrimary vaccination†: 1 dose at age 11–12 yrs



Booster: 1 dose at age 16 yrs if first dose administered before 16th birthday



Catch-up vaccination: Although routine vaccination is only recommended for adolescents aged 11–18 yrs, MenACWY may be administered to persons aged 19–21 yrs who have not received a dose after their 16th birthday



Note: MenACWY vaccines are interchangeable



Primary vaccination: MenB series at age 16–23 yrs on basis of shared clinical decision-making (preferred age 16–18 yrs)• MenB-FHbp§: 2 doses at 0 and 6 mos• MenB-4C: 2 doses ≥1 mo apart



Booster: MenB booster doses not routinely recommended except for previously vaccinated persons who become or remain at increased risk. 



Note: MenB-FHbp and MenB-4C are not interchangeable



≥24 yrsNot routinely recommended



See Table 3 for persons at increased risk



Not routinely recommended



See Table 3 for persons at increased risk