Meningococcal disease (meningococcemia) facts

This photo depicts purple necrotic lesions on the legs of a person who has meningococcemia.

• Meningococcal disease (meningococcemia) is a bloodstream infection caused by the bacterium Neisseria meningitidis, also called meningococcus.
• N. meningitidis is a contagious bacterium that spreads from person to person via respiratory secretions.
• Initially, patients present with fever and general body aches. A rash is often present. Patients with meningococcemia are usually seriously ill.
• Complications include septic shock, failure of multiple organs, lack of circulation to the extremities (with loss of limbs), and death. Patients may also develop or present with bacterial meningitis.
• Intravenous antibiotics treat meningococcemia.
• Early treatment reduces the risk of complications and death.
• Four types (serogroups) of N. meningitidis cause most cases of meningococcal disease. A vaccine is available to help prevent four of the five serogroups. Medical professionals recommend that children get the vaccine at 11 years of age, with a booster dose at 16 years of age. People at high risk of getting the infection should also get the vaccination. People without a missing spleen or a specific type of defect in their immune system are called complement deficiency. Doctors should monitor people undergoing treatment with complement inhibitor drugs such as eculizumab (Soliris, an anti-C5 humanized monoclonal antibody) because they are at very high risk, even if vaccinated.
• People with HIV are also at increased risk for meningococcal disease and should be vaccinated.
• People who travel to areas where outbreaks are occurring should be vaccinated before travel.
• College students and military recruits who will be living in dormitories should be vaccinated if they were not vaccinated at an earlier age.
• People who have had close contact with an infected patient (for example, health professionals, household members with face-to-face contact, playmates, etc.) should receive “prophylactic” antibiotics (chemoprophylaxis) to reduce the risk of disease. This should begin as soon as possible but certainly within two weeks of exposure.

What is meningococcemia?

Meningococcal disease (meningococcemia) is a bacterial infection of the blood due to Neisseria meningitidis, also called meningococcal bacteremia or meningococcal sepsis. As the name suggests, this bacterium is best known for causing meningococcal meningitis, which occurs in up to 20% of those with meningococcemia. Up to 75% of those with meningococcal meningitis will also have bacteremia.

Many bacteria can cause bloodstream infections (septicemia), including staphylococci, Streptococcus B, or Streptococcus A. In addition, other bacteria can cause meningitis, including Streptococcus pneumoniae or leptospirosis. However, N. meningitidis is the commonest cause of bacterial meningitis in the U.S. It is more readily contagious from person to person than these other bacteria and causes rapidly progressive and severe disease (fulminant meningococcemia). Rates of infection are typically highest in older children and adolescents, although there are reports of meningococcemia in all age groups. People with a deficiency of the complement immune system and those taking complement inhibitors (eculizumab [Soliris]) are at high risk for severe meningococcal disease, even if they are vaccinated.

Other forms of meningococcal disease include pneumonia in up to 15% of cases and much less often bacterial (septic) arthritis, otitis media (middle ear infection), and other conditions.

The case-fatality rate of meningococcal disease is high,

• up to 15%, even with antibiotic treatment;
• it is up to 40% with bacteremia.
• Up to 20% who survive have disabilities like deafness, neurologic problems, or amputations.

What causes meningococcemia?

N. meningitidis, or meningococcus, is a gram-negative bacillus. Under the microscope, the bacteria usually appear in pairs (diplococcus), like two small kidney beans side by side. Meningococcemia is another term for widespread bloodstream infection.

Humans are the only known source (reservoir) for meningococcal infection. Some people can harbor the bacteria in their throats and not get sick (a “carrier” state), but others develop an infection. Either can transmit the bacteria.

• People usually acquire meningococcus by breathing in respiratory droplets or by direct contact with oral secretions by sharing eating utensils, kissing, etc.
• The presence of a capsule made of complex carbohydrates called polysaccharides increases the infectiousness, or virulence, of N. meningitidis. This capsule protects the bacteria from the initial immune defenses of the nose and throat.
• Once the bacteria colonize the nasopharynx and multiply, they may invade the tissues and enter the bloodstream to cause meningococcal septicemia. This may cause low blood pressure and septic shock.
• From the blood, they may penetrate between the cells that form the blood-brain barrier to infect the cerebrospinal fluid. This causes bacterial meningitis, or infection of the meninges (or meninx, one of the membranes surrounding the brain and spinal cord).

There are several different types (at least 12 serogroups) of N. meningitidis.

• Serogroups A, B, C, Y, and W cause most meningococcal diseases, especially outbreaks.
• In the U.S., Europe, and Australia, serogroups B, C, Y, and less often W cause most infections.
• Serogroup A causes most of the large epidemics, with A and W causing outbreaks in North Africa around the Hajj pilgrimage.
• Serotype C caused an outbreak among men who have sex with men in California in August 2016.
• Serotype B tends to cause more sporadic cases rather than epidemics.

What are risk factors for meningococcemia?

Children and adolescents 5 to 19 years of age are at the highest risk for meningococcemia. Newborns acquire antibodies from their mothers via the placenta, although these antibodies fade after a few weeks or months. Toddlers are not immune, and there have been several exposures in daycare settings. As children age, they gradually gain immunity to meningococcal strains by coming into contact with milder strains of the bacteria. However, because this immunity is imperfect, it is still possible for adults to get meningococcal disease. In the U.S., medical professionals routinely administer the meningococcal vaccine to children in the preteen and teen years.

HIV infection is a risk factor for invasive meningococcal infection. On Aug. 16, 2016, after 24 cases of meningitis arose in men who have sex with men (MSM), two of whom had HIV, California public health officials issued an advisory recommending meningococcal vaccination of all HIV-infected people and MSM who planned to travel to the area. This was the largest meningococcal outbreak in MSM in the U.S.

The complemented part of the immune system is critical in fighting off meningococcal disease. Patients who have a history of a specific genetic deficiency in the complement system, or who are taking an anti-complement drug for certain diseases, are at high risk for severe disease. The spleen is necessary for an effective immune response against encapsulated bacteria, so people are at higher risk for fulminant meningococcemia if they have had their spleens taken out (asplenia) or have spleens that function poorly (hyposplenism).

People who have been in close contact with an infected person for a long time are at increased risk to acquire the disease. People who live together in close quarters, such as military barracks or college dormitories, are at special risk for disease because one infected person can spread the disease to many others. One study showed that the attack rate in household contacts was 500 times greater than that of the general population.

In some parts of the world, outbreaks of meningococcal disease occur regularly. This is true of a group of countries in sub-Saharan Africa (the “meningitis belt”) where epidemics occur every five to 10 years, with an attack rate of up to 1,000 cases per 100,000 population (compared to up to three per 100,000 population in the rest of the world).

Outbreaks have occurred during the Islamic Hajj pilgrimage. Over 2 million Muslims from over 180 countries visit Saudi Arabia during the Hajj. The pilgrimage is long and arduous. Heat, throat irritation by dust, dense overcrowding, and inadequate hygiene contribute to infection. Saudi Arabia now requires proof of meningococcal (ACWY) vaccination on an International Certificate of Vaccination or Prophylaxis before admitting pilgrims. This has greatly reduced the occurrence of meningitis.

What are symptoms and signs of meningococcemia?

Infected patients initially experience

Once symptoms appear, the disease usually gets rapidly worse over several hours. In a minority of cases, symptoms continue at a low-grade level for several days.

If meningitis is present,

Common meningococcemia symptoms

• As the symptoms worsen, shaking chills and high fever occur.
• The rash is common and appears like small red dots (petechiae) or a bleed into the skin (purpura) associated with vasculitis, or inflammation of small blood vessels.

Severe meningococcemia symptoms

• With severe meningococcal disease, vasculitis may be extensive and severe enough to cause death or necrosis of the skin (purpura fulminans).
• The petechial or purpuric rash may appear anywhere on the body, even on the palms or soles or inside the mouth. It may be limited to a small section of the body or cover extensive areas. Thus, a careful physical examination of the skin and mucosal surfaces is important.
• Petechiae do not disappear or blanche when compressed; one way to diagnose them is to press a clear glass against the skin to see if they disappear.
• Petechial rash in a person with fever should raise concern for life-threatening meningococcal disease and the need for prompt antibiotics.
• In addition to the petechial rash, physical examination reveals a fast heart rate and often low blood pressure, and other signs of septic shock.
• Laboratory examination usually shows increases in white blood cell counts and may show low platelet counts (thrombocytopenia).
• The bacteria may spread to the heart, causing myocarditis, or inflammation of the heart muscle. In severe cases, multiple organ systems may fail, including the kidneys, lungs and airways, liver, or heart.
• Fulminant meningococcemia is a rapidly progressive and life-threatening disease.
• Uncommonly, the bacteria may cause a low-grade bloodstream infection (chronic meningococcemia) with fever, joint pain, and rash that lasts one to three weeks.
• Severe low blood pressure and vasculitis may cause necrosis of the hands and feet, requiring amputation.

Although meningococcemia refers to an infection of the bloodstream.

• It is important to note that up to 15% will develop meningococcal meningitis.
• Meningococcal sepsis poses a higher risk of shock and death than meningococcal meningitis alone.
• Although defined differently and having different prognoses, there is a significant overlap between meningococcemia and meningococcal meningitis.

How do health care professionals diagnose meningococcemia?

A patient’s history and physical exam may suggest a diagnosis of meningococcemia, although a definitive diagnosis requires laboratory testing. Because the disease can progress rapidly, patients should start treatment promptly without waiting for laboratory test results. Health care professionals diagnose meningococcal infection by culturing N. meningitidis from blood cultures. The bacteria grow in one to two days in most cases, and medical professionals use biochemical methods to identify them as N. meningitidis. Samples of the growth can also be stained and examined under the microscope to detect the characteristic double kidney bean (diplococcus) appearance of the bacteria, although additional biochemical tests are performed to confirm the identification of the organism. Once the organism is growing on a culture medium, medical professionals perform tests to determine which antibiotics are likely to kill the bacteria (susceptibility testing) because increased resistance to several antibiotics has been documented.

In some instances, skin biopsies from the rash can reveal the organisms under the microscope, but this is difficult and a negative result is not a reliable means of ruling out meningococcemia. Investigators have used a PCR (polymerase chain reaction) laboratory test to detect N. meningitidis in the blood, although they developed the test for spinal fluid. The drawbacks of PCR are that it cannot determine how susceptible the bacteria are too specific antibiotics and that the test is not available in all hospital laboratories.

What is the treatment for meningococcemia?

• Meningococcal disease is a very severe bacterial infection often requiring intensive care monitoring.
• The most important treatment for meningococcemia is early intravenous antibiotic therapy. Start antibiotics as soon as meningococcemia is suspected.
• A third-generation cephalosporin (ceftriaxone [Rocephin], cefotaxime [Claforan]) is the initial treatment of choice.
• Once investigators have identified cultures with susceptibilities to antibiotics, the antibiotic regimen may be adjusted.
• In addition to intravenous antibiotics, patients in the intensive care unit will likely require intravenous fluids and sometimes medications (vasopressors) to help maintain and support adequate blood pressure.
• Some patients may require ventilator support if they develop respiratory distress.
• Those with kidney failure may need hemodialysis.

What types of doctors treat meningococcemia or meningococcal disease?

• Primary care health professionals such as internists, family practice specialists, pediatricians, and emergency room specialists may be the first clinicians to evaluate and suspect meningococcemia.
• Critical care specialists, infectious disease specialists, and nephrologists (kidney or renal specialists) may treat people who are seriously ill or have meningitis or have immune suppression in the hospital or intensive care unit.

What is the prognosis of meningococcemia?

• Despite antibiotic therapy and intensive care monitoring, meningococcemia still has overall case fatality rates of 40% in the United States.
• Up to 19% have long-term complications from the meningococcal infection.

These complications could include

• amputation of limbs due to ischemia or low blood pressure,
• adrenal insufficiency from adrenal hemorrhage (Waterhouse-Friderichsen syndrome),
• neurological disabilities such as deafness, bacterial arthritis, need for skin grafting, and other problems.