Meningococcal Disease (Meningococcemia)

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

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.

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.

Infected patients initially experience

• fatigue,
• fever,
• nausea,
• headache, and
• body aches, similar to those experienced by people with influenza, including swine flu or bird flu.

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,

• headache,
• stiffness or resistance to bending the neck forward, and
• difficulty tolerating light (photophobia) are prominent features.

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.

• 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.

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.

• 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.

• 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.

There are several ways to prevent meningococcemia.

• Infected people are contagious, and health care providers will place them in private isolation rooms in the hospital.
• Health care workers will wear masks and gloves when entering the room to administer care.
• Isolation duration varies but usually lasts at least 24 hours after the start of intravenous antibiotics.
• People who have come in contact with an infected patient should strongly consider taking antibiotics to reduce the risk of disease, a process called prophylactic treatment or chemoprophylaxis.
• Physicians may have patients take prophylactic antibiotics such as rifampin (Rifadin) or ciprofloxacin (Cipro) in pill form.
• Sometimes they will administer a shot of ceftriaxone.
• The choice of antibiotic is based on the age of the patient, resistance patterns in the community, and whether the person is pregnant or not.
• Close contact usually means household contacts, daycare or child care contacts, or those exposed to potentially infected saliva in the week before the patient got sick.
• Routine patient care does not warrant prophylaxis in health care workers, unless the worker has had very close contact with respiratory secretions, such as when giving mouth-to-mouth resuscitation or inserting a breathing tube.
• People should begin prophylaxis as soon as possible after the exposure but certainly within two weeks of the event. The antibiotics help eliminate the carriage of the bacteria and physicians may also use them in the final step of treatment for infected patients.
• Doctors should monitor people exposed to N. meningitidis for 10 to 14 days to make sure they do not develop symptoms.
• Caretakers and health care workers should wash their hands frequently to minimize the transfer of infected secretions to the mouth or nose.

Meningococcal disease is vaccine-preventable.

• There are very effective and safe vaccines available for all five serogroups, but no single vaccine covers all five.
• A quadrivalent conjugate vaccine covers four major disease-causing serogroups (A, C, Y, W-135).
• There are two types of vaccines available in the United States in this category (Menactra, Menveo).
• Two other vaccines cover serogroup B (Bexsero, Trumenba).
• The choice of the vaccine depends on the age of the patient and specific risk factors.
• Vaccine side effects are usually mild, consisting of a sore arm.
• Allergic reactions may occur but are very rare.
• Physicians recommend the ACWY-135 conjugate vaccine as routine for all children starting at 11 years of age in the U.S. Children should get a booster dose at 16 years of age when the incidence of meningococcal disease is highest.
• Teens who are 16 years of age or older and have never been vaccinated against meningococcal disease need only a single dose.

In people ages 2 months to 10 years old, physicians recommend the conjugate vaccine for

• those with absent spleen or dysfunction,
• those living with HIV,
• those with immune deficiencies of complement (terminal complement or C5-9 deficiency, properdin deficiency, factor H or factor D deficiency), and
• those traveling to areas where the disease is common.

In adults, the recommendations for conjugate ACWY-135 are as below:

• military recruits,
• first-year college students living in dormitories (if not received less than 5 years before starting),
• individuals with absent spleen or dysfunction,
• people living with HIV,
• people with immune deficiencies of complement (terminal complement or C5-9 deficiency, properdin deficiency, factor H or factor D deficiency),
• people taking a complement inhibitor (eculizumab [Soliris]),
• travelers to areas where the disease is common,
• researchers, microbiologists, or laboratory staff who may work with N. meningitidis, or
• people living in a serogroup ACWY outbreak area.

In some situations where an individual remains at high risk, doctors perform revaccination after five years. Doctors may also consider serogroup B vaccine at age 16-18, however, serogroup B vaccine is recommended in teens age 16-23 and adults as below:

• individuals with absent spleen or dysfunction,
• people with immune deficiencies of complement (terminal complement or C5-9 deficiency, properdin deficiency, factor H or factor D deficiency),
• people taking a complement inhibitor (eculizumab, [Soliris]), and
• people living in a serogroup B outbreak area.

Health care providers will take special care in giving serogroup B vaccine to infants and children with poor spleen function or who live with HIV. Those ages 2-23 months should receive the Menveo brand of serogroup B vaccine or wait until age 2 to receive Menactra. At that time, they should receive the conjugate pneumococcal vaccine (PCV-13) first, followed by Menactra. This is because the latter may interfere with the development of pneumococcal antibodies.

People taking eculizumab (Soliris) remain at high risk for invasive meningococcal disease, and physicians will monitor them for symptoms even if vaccinated.

Outbreaks of meningococcemia or meningococcal disease occur sporadically around the world but occur more predictably in sub-Saharan Africa. Health care providers should administer the ACWY conjugate vaccine to travelers visiting these areas. Those with special risk factors above should get the serogroup B vaccine. As mentioned above, Saudi Arabia requires proof of vaccination for travelers during the Hajj.

In addition to vaccination, respiratory etiquette (cover coughs and sneezes with the elbow or disposable tissue) and hand hygiene (frequent washing with soap and water or ethanol-based hand sanitizer) are very helpful in preventing infections in general.