Meningococcemia may be preceded by an infection of the upper respiratory tract. Septicemia itself manifests in form of chills, fever, headache, nausea, vomiting and generalized skin rash that develop within a very short time . Additionally, petechiae, purpura and ecchymoses may become visible . These dermatological symptoms are usually considered the earliest pathognomonic sign for septicemia. In some cases, areas of skin may become gangrenous. Diarrhea has been observed.
Peracute onset of symptoms resembles Waterhouse Friderichsen syndrome. The latter describes a fulminant form of septicemia and may be triggered by meningococci, pneumococci and other bacterial species. Progression is extremely rapid, high fever is developed and skin rash affects the whole body within hours. Often, severe hypotension is already detected during first examination, fever may subsequently turn into hypothermia and patients are at great risk of septic shock and multi organ failure .
Of note, chronic meningococcemia has been described. It is marked by periods of remission and exacerbation that may occur over the course of months. Fever, overall weakness, headache and skin rash come and go.
Patients suffering from meningococcemia may also present meningococcal meningitis. Typical symptoms for meningitis are fever, headache, photophobia, nausea, vomiting and a stiff neck. Due to inflammation of the meninges, movements of the cervical spine may be painful and the corresponding muscles are usually tensed. This symptom complex is also known as meningismus and is not pathognomonic for meningococcal meningitis.
Because N. meningitidis is a facultative pathogen that causes severe meningococcal disease primarily in immunodeficient patients, other symptoms may be present that result from underlying diseases and immunosuppression itself. For instance, infections of the respiratory tract are not necessarily cured when meningococcemia occurs.
Anamnesis and clinical examination may prompt a suspicion of meningococcemia, especially if patients also present with signs of meningitis. However, they do not allow for a definitive diagnosis. The latter requires obtaining samples of blood and cerebrospinal fluid and establishing bacterial cultures. By no means, initiation of treatment should be delayed until the results of laboratory analyses are available. This may take several days. Rapid latex agglutination tests and other biochemical methods may serve to obtain preliminary results.
Aiming at immediate identification of the causative pathogen, skin biopsies have been used for microscopic examination. N. meningitidis are diplococci and detection of microorganisms organized in such a way strongly supports diagnosis of meningococcal disease. However, false negative results are common .
Skin biopsies may nevertheless be they key to an improved diagnosis of meningococcal disease: Newer research focuses on developing molecular biological methods to provide information about the etiologic agent in much shorter periods of time. Polymerase chain reactions may be conducted with nucleic acids isolated from such tissue samples and so far, results are highly promising . The challenge is to design primers that allow amplification of gene sequences carried by as many serotypes as possible. Otherwise, specific tests would have to be carried out for each serotype that differs . Also, molecular biological methods may not be universally available.
Meningococcemia is generally treated with beta-lactam antibiotics like penicillin. While penicillin is usually not effective against gram-negative bacteria, it does kill gram-negative cocci such as Neisseria. This antibiotic drug is not only effective, but also rather inexpensive and easily available even in underdeveloped countries. In case of penicillin allergy, cephalosporins may be applied .
In case of survival of severe meningococcemia, long-term sequelae due to persistent vascular problems may require additional medical attention . Ischemia may be irreversible and cause gangrenous alterations. In such cases, an amputation may be indicated. Orthopedic sequelae are not uncommon either and should be treated accordingly.
Prognosis is good if an adequate treatment is provided in a timely manner. Any delay regarding the initiation of therapy considerably worsens the outcome. Septic shock is associated with a doubtful prognosis and mortality rates in shock patients amount up to 50% . Shock may lead to disseminated intravascular coagulation and multi organ failure, which are very unfavorable prognostic parameters that are associated with mortality rates of up to 90%.
Causative agent of meningococcemia is N. meningitidis, a gram-negative, facultatively anaerobic diplococci that replicates intracellularly . There are different serogroups of N. meningitidis, the most important ones being A, B, C, W135 and Y. These serotypes account for more than 90% of all infections.
N. meningitidis demand special media for bacterial culture, e.g., blood agar plates. They are also rather slow growing, which is why confirmation of infection with Neisseria and identification of the serotype takes several days. Nevertheless, bacterial culture is still considered the gold standard for diagnosis of meningococcemia. Although latex agglutination tests may also be carried out, they are less specific. Samples of blood, cerebrospinal fluid and even scrapings of skin lesions are suitable for such testing.
N. meningitidis may colonize mucous membranes of the upper respiratory tract without triggering any symptoms. While such carriers, mainly immunocompetent individuals, may never develop meningococcemia, they are of great epidemiological importance since they usually don't receive any treatment but pass pathogens to other people. They may remain infectious for months. Close contact with carriers or patients bears a high risk of infection since N. meningitidis is spread by means of airborne droplets. Although few cases are known where health care givers contracted the disease from patients they were working with, this possibility should not be underestimated and adequate preventive measures are highly recommended. This also applies to laboratory personnel.
Infections with N. meningitidis may cause meningococcemia, meningitis or both of these conditions. While some sources state that less than 10% of affected individuals present with sole meningococcemia, others have published this share of patients to amount to 50%. Fulminant meningococcemia, also termed Waterhouse Friderichsen syndrome, is not a rare occurrence.
N. meningitidis may cause epidemics as well as sporadic disease. There seems to be a relation between the likelihood for epidemics and the respective serotype of the bacterium. In fact, most epidemics are caused by serotype A which is distributed throughout Africa and Asia. African countries located between 20° of northern latitude and 10° of southern latitude, approximately, have been designated the "African meningitis belt" due to particularly high incidence rates of meningitis. Risks are particularly high for children and meningococcal disease is associated with a high mortality in pediatric patients .
N. meningitidis serotype B is mainly found in Europe and America, while serotype C is distributed worldwide. Of note, travelers may contract the disease in foreign countries, turn home without having developed any symptoms and infect their fellows  .
Septicemia due to N. meningitidis dissemination is primarily associated with endothelial damage, consecutively increased vascular permeability and activation of the coagulation cascade.
Endothelial lesions are primarily mediated by endotoxins, i.e., by lipopolysaccharides that form the cell membrane of gram-negative bacteria such as Neisseria . Meningococcemia also induces an intravascular immune response, activation of immune cells and release of pro-inflammatory cytokines as well as reactive oxygen species . These further contribute to vascular damage and may additionally mediate vasodilation.
Vascular permeability rises due to injury of the vessel's inner layer. The subsequent shift of fluids from intravascular to extravascular compartments results in hypotension and this condition is further aggravated by generalized vasodilation.
On the other hand, endothelial damage triggers adhesion and aggregation of thrombocytes and deposition of fibrin. The latter requires a plethora of coagulation factors to interact. Because of excess consumption of thrombocytes and coagulation factors due to generalized activation of coagulation, patients finally develop a disseminated intravascular coagulopathy.
The aforementioned pathophysiological events may lead to septic shock that manifests in form of fever, reduced cardiac output and diminished myocardial contractility, severe hypotension due to vasodilation and increased vascular permeability, disseminated intravascular coagulation and ultimately multi organ failure and death.
Of note, meningococcemia also allows bacteria to reach the meninges, establish an intracranial infection, meningitis and an increase of intracranial pressure. And while meningococcal meningitis is not the topic of this article, it is a direct consequence of meningococcemia and has major clinical relevance.
As has been mentioned above, most cases are caused by serotypes A, B, C, W135 and Y. Quadrivalent vaccines able to confer protection against serogroups A, C, W135 and Y are available as well as formulations that include certain serotypes of N. meningitidis and other pathogens . There are approved products for infants, children, adolescents, adults and the elderly.
Recommendations regarding general vaccination differ with geographical regions and predominating serotypes. In several countries, it is recommended to firstly vaccinate children aged 12 years and to maintain protection during adulthood. Earlier and later vaccination should be considered for patients with higher risks of contracting the causative pathogen and developing meningococcal disease. Risk groups are:
Temporal restrictions may not allow for an effective vaccination of first aiders and emergency staff who assist in epidemic regions. Similarly, non-vaccinated individuals pertaining to any of the aforementioned risk groups may suddenly find themselves in an epidemic area without an opportunity to protect themselves by vaccination. Family members of patients suffering from meningococcemia are also at risk. In these cases, antibiotic prophylaxis is recommended. Cephalosporins, fluoroquinolones and other compounds may be used to this end.
Neisseria meningitidis (N. meningitidis) is a gram-negative diplococcus that replicates intracellularly. It is often considered facultatively pathogenic since colonization of the upper respiratory tract does not necessarily induce any disease. N. meningitidis is contracted via droplet infection and people who carry these bacteria in their nasopharynx may easily spread it.
Infection may lead to upper respiratory infection and subsequent septicemia, whereby the latter is called meningococcemia in this particular case. During septicemia, N. meningitidis disseminates by means of the vascular system, may reach the meninges and provoke meningococcal meningitis. However, meningitis is not an exclusion criterion for meningococcemia or vice versa . Patients may present with either of the two conditions or a combination of both. Data regarding the share of patients pertaining to any of these three subgroups varies largely.
Therapy strongly depends on the presence of either pathogenic feature and has to be initiated as soon as possible since both meningococcemia and meningitis are associated with high rates of mortality. In detail, meningococcemia may lead to disseminated intravascular coagulopathy, severe hypotension and septic shock within hours after symptom onset. In this context, generalized skin rash may be the earliest and thus most important sign of septicemia. Fever, nausea and vomiting are less specific. Treatment consists of systemic antibiotic therapy and supportive measures.
Neisseria meningitidis is a bacterium that lives in nose and throat of possibly asymptomatic carries. It is passed to other individuals by droplet infection, i.e., close contact with a carrier or a person suffering from meningococcal disease increases the risk of contracting the pathogen.
Patients with a weakened immune system are particularly at risk to develop the aforementioned disease. Here, bacteria spread throughout the body and may reach the meninges. Bacterial spread is referred to as meningococcemia; infection of the meninges results in meningococcal meningitis.
Acute onset of fever, headache, nausea, vomiting and skin rash are characteristic for meningococcemia. Dermatological symptoms may manifest first on arms and legs and subsequently spread over the whole body. In severe forms of meningococcemia, this may occur within hours.
Presence of bacteria in the blood stream may trigger a potentially life-threatening cascade of events leading to septic shock. This condition is marked by increased vascular permeability, generalized coagulation and consecutive bleeding tendency, severe hypotension and multi organ failure. In order to avoid these pathophysiological events, therapy should be initiated as soon as possible.
Medical history and clinical examination only allow for a tentative diagnosis. In order to confirm meningococcemia, the causative agent has to be isolated from blood samples or other affected tissues and needs to be grown in bacterial cultures. This procedure takes several days and will be done, but treatment needs to be started much earlier.
Treatment consists in antimicrobial therapy and supportive measures. Several antibiotics are effective against Neisseria meningitidis and although penicillin is most frequently used, there are alternatives for patients presenting with penicillin allergy.