Meningococcal disease is a serious, vaccine-preventable infection caused by Neisseria meningitidis, a gram-negative diplococcus bacterium also known as meningococcus. Meningococcal disease presents as life-threatening and rapidly progressive meningitis (infection of the protective membranes surrounding the brain and spinal cord), meningococcal septicemia (infection of the bloodstream), or a combination of both. Initial symptoms are flu-like and generally nonspecific, including fever, headache, neck stiffness, nausea, vomiting, and neurological symptoms including photophobia and confusion. A purple non-blanching rash may also be present. As infection progresses, septic shock eventually leads to gangrene and organ failure. Left untreated, meningococcal disease has an 80% mortality rate. With proper treatment, the mortality rate drops to 4–20%, with roughly 20% of survivors experiencing long-term complications including brain damage, blindness, deafness, and amputation.
Neisseria meningitidis colonizes the nasopharynx of roughly 10% of the population without symptoms, but meningococcal disease can develop in rare cases when the bacteria enter the bloodstream. Meningococcal disease is transmitted by respiratory droplets or saliva from anyone who carries the bacteria in their respiratory tract, including asymptomatic individuals, although transmission usually requires close or lengthy contact. Symptoms usually begin three to four days after exposure. Almost all cases of meningococcal disease are caused by one of six encapsulated serotypes of N. meningitidis: A, B, C, W, X, and Y. Risk factors for infection include immunodeficiency, especially in cases of complement component deficiencies and low or absent spleen function. Diagnosis is often suspected based on symptoms and confirmed by culture or PCR finding N. meningitidis in the blood or cerebrospinal fluid.
Several vaccines against meningococcal disease have been developed against all six disease-causing serotypes and have significantly reduced the incidence of disease. The United States CDC recommends the vaccine for all adolescents, along with children and adults at increased risk of infection. The World Health Organization recommends mass vaccination in areas with high rates of meningococcal disease. Meningococcal disease is treated with antibiotics; cephalosporins are generally the first-line treatment. In severe cases, additional supportive care may be necessary, and necrotic limbs may require amputation. In rarer cases, atypical presentation of meningococcal disease may occur in the form of pneumonia, septic arthritis, and other infections.
Predominant disease-causing serotypes differ by country and age group, with serotype B accounting for most new cases worldwide. Most cases in the developed world are sporadic, with outbreaks rarely occurring in residential settings such as college campuses. In the United States, incidence is highest among children under 5, young adults, and older adults. In some regions, such as the African meningitis belt, meningococcal disease is endemic and outbreaks are more frequent. In 2012, an estimated 1.2 million cases of meningococcal disease occurred worldwide, resulting in roughly 135,000 deaths.
Signs and symptoms
Meningococcal disease refers to a broad spectrum of conditions caused by invasive Neisseria meningitidis infection. It typically presents in two primary forms: meningitis and meningococcal septicemia. Meningitis is the most common presentation, representing roughly half of U.S. cases; in meningococcal meningitis, N. meningitidis invades the meninges, protective membranes surrounding the central nervous system. Meningococcal septicemia, in which N. meningitidis invades the bloodstream and triggers a life-threatening immune response known as sepsis, presents without meningitis in roughly 30% of U.S. cases. Many cases involve both meningitis and sepsis. Symptoms generally begin three to four days after exposure.
Initial symptoms appear as flu-like illness, which can be problematic due to the necessity for prompt treatment. Meningococcal meningitis typically presents with sudden onset of fever, headache, neck stiffness, nausea, vomiting, and myalgia (muscle pain). Meningitis also causes neurological symptoms, including altered mental status and photophobia (sensitivity of the eyes to light). Kernig's sign and Brudziński's sign can confirm meningitis, but each have low sensitivities and cannot exclude illness. The classic "triad" of meningitis symptoms consists of fever, neck stiffness, and altered mental status; however, all three symptoms are present in less than half of meningitis cases. Infants may present with different symptoms, including inactivity, irritability, poor feeding, and abnormal reflexes. There may also be a bulge in the anterior fontanelle at the top of the head. Meningococcal septicemia, also known as meningococcemia, also causes flu-like symptoms that are difficult to differentiate from other illnesses. Initial symptoms of sepsis include fever, chills, diarrhea, nausea, vomiting, fatigue, and muscle and joint pain. Other common signs include hypotension (low blood pressure) and tachycardia (high heart rate).
Another hallmark sign of meningococcal disease is bleeding under the skin, causing purple bruising known as petechiae (less than 3 mm in diameter) or purpura (3–10 mm). Bleeding under the skin can be confirmed if rolling a glass over the skin does not cause the rash to fade.
Complications Meningococcal disease is a rapidly progressive disease, and without treatment can quickly lead to extensive complications. Even with treatment, one in five survivors experience long-term complications. Like other gram-negative infections, N. meningitidis releases endotoxin, causing disseminated intravascular coagulation (DIC), a condition in which blood clots block small blood vessels. As available clotting factors are used up, bleeding occurs throughout the body and blood vessels are damaged. Sepsis eventually leads to tissue death (necrosis) and organ failure throughout the body. Tissue death is most common in the limbs, which may require amputation after treatment. If hemorrhaging affects the adrenal glands, Waterhouse–Friderichsen syndrome can occur, causing deadly adrenal insufficiency. Meningitis may cause irreversible brain damage, blindness, deafness, and other neurological problems.
Atypical presentations of meningococcal disease While meningitis and sepsis are the two most common complications of meningococcal disease, in rarer cases, N. meningitidis can infect and cause complications in other parts of the body. In about 15% of cases, meningococcal disease presents as bacterial pneumonia; this is the most common presentation in adults over 65. This is a multi-lobar, rapidly evolving pneumonia, sometimes associated with septic shock. With prompt treatment, the prognosis is excellent.
Meningococcal disease can also cause septic arthritis, in which N. meningitidis infects joints, causing inflammation. Septic arthritis presents with joint pain, redness, warmth, and restricted joint movement. It most commonly affects the knee and is usually confined to one joint. Meningococcal disease can cause gastrointestinal symptoms in some cases, including nausea, vomiting, and abdominal pain, which can result in misdiagnosis. In rare cases, meningococcal disease can affect the pericardium, the sac surrounding the heart, causing pericarditis.
Although not considered within the definition of meningococcal disease, N. meningitidis has been found to cause urethritis in men, causing urethral discharge and pain or discomfort during urination.
Cause and transmission
Meningococcal disease is caused by infection by the bacterium Neisseria meningitidis. Also known as the meningococcus, N. meningitidis is a gram-negative diplococcus that colonizes the nasopharynx of around 5–10% of the population as a commensal organism. Meningococcal disease develops in rare cases when N. meningitidis enters the bloodstream, rapidly leading to systemic infection. While there are 13 identified serotypes of N. meningitidis, almost all cases of meningococcal disease are caused by one of six serotypes with polysaccharide capsules: A, B, C, W, X, and Y.
Meningococcal disease is transmitted by respiratory droplets or saliva from an individual who carries N. meningitidis in their respiratory tract. Therefore, it can be spread both by asymptomatic carriers and people with meningococcal disease. However, it is generally not very contagious, and close contact is usually required for transmission.
Pathogenesis Meningococcal disease causes life-threatening meningitis and sepsis conditions. In the case of meningitis, bacteria attack the lining between the brain and skull called the meninges. Infected fluid from the meninges then passes into the spinal cord, causing symptoms including stiff neck, fever, and rashes. The meninges (and sometimes the brain itself) begin to swell, which affects the central nervous system.
Even with antibiotics, approximately 1 in 10 people who suffer from meningococcal meningitis will die; however, a similar proportion of survivors are affected by limb loss, hearing impairment, or permanent brain damage.Centers for Disease Control and Prevention. Meningococcal disease among college students: ACIP modifies recommendations for meningitis vaccination. Press release. 1999 Oct 20 The sepsis type of infection is much more deadly, and results in a severe blood poisoning called meningococcal sepsis that affects the entire body. In this case, bacterial toxins rupture blood vessels and can rapidly shut down vital organs. Within hours, patients' health can change from seemingly good to mortally ill.
The N. meningitidis bacterium is surrounded by a slimy outer coat that contains disease-causing endotoxin. While many bacteria produce endotoxin, the levels produced by meningococcal bacteria are 100 to 1,000 times greater (and accordingly more lethal) than normal. As the bacteria multiply and move through the bloodstream, it sheds concentrated amounts of toxin. The endotoxin directly affects the heart, reducing its ability to circulate blood, and also causes pressure on blood vessels throughout the body. As some blood vessels start to hemorrhage, major organs like the lungs and kidneys are damaged.
Patients with meningococcal disease are treated with a large dose of antibiotic, like penicillin or cephalosporins. The systemic antibiotic in the bloodstream rapidly kills the bacteria, with some harmful bacterial mass and endotoxin being released in the process of lysis. There is a lack of evidence that this phenomenon is clinically significant, with studies pointing to an overall decrease in endotoxin release with antibiotic treatment in comparison to leaving it untreated. It may take several days for the toxin to be neutralized by the body through continuous liquid treatment and antibiotic therapy due to inflammatory responses and the initial amount of bacteria.
Diagnosis
Diagnosing meningococcal disease is vital, as death can occur in a person within 6–12 hours of initial signs and symptoms. Therefore, if diagnosis can be suspected based on symptoms, treatment should begin even before the diagnosis is confirmed. The gold standard for diagnosis of meningococcal disease is the isolation of Neisseria meningitidis from sterile body fluids, usually the cerebrospinal fluid by lumbar puncture or the blood. Testing of the synovial fluid in the joints or pleural fluid in the lungs can confirm septic arthritis or pneumonia, respectively, caused by N. meningitidis.
If a patient presents with evidence of elevated intracranial pressure, such as altered mental status or focal neurological deficits, a lumbar puncture should be avoided because of the risk of brain herniation In these cases, a computer tomography (CT) scan can assist diagnosis.
Prevention