Meningococcemia can cause a wide range of clinical diseases, of which neisserial meningitis is the most severe and life-threatening. The bacteria, Neisseria meningitidis, is capable of causing septicemia, pneumonia, and meningitis. These are all relentless diseases that are universally fatal if not promptly treated. The bacteria has been known to cause severe disseminated intravascular coagulation (DIC) and the Waterhouse-Friderichsen syndrome. The latter syndrome, also known as acute adrenocortical insufficiency, is directly caused by hemorrhagic destruction of both adrenal glands. This syndrome can result from a wide range of conditions, including infections, and N. meningitidis is one of the more frequent infectious causes.
Clinical Findings: Children younger than 1 year of age are those most likely to develop disease from N. meningitidis infection. Boys are more apt to develop this infection than girls, and there is no race predilection. One risk factor appears to be the presence of a smoker in the household. It is theorized that the secondhand smoke damages the child’s respiratory epithelium just enough to allow the bacteria to penetrate the mucous membranes and enter the bloodstream. Other risk factors include a deficiency of the complement components C5, C6, C7, and C8. Asplenia also increases one’s risk, because the spleen is extremely important in removing encapsulated bacteria from the bloodstream. Chronic immunosuppression increases the risk, as does living in crowded conditions. This is why military barracks and college dormitories are often sources of outbreaks.
ACUTE ADRENAL INSUFFICIENCY (WATERHOUSE-FRIDERICHSEN SYNDROME)
Patients who develop meningitis have fever, head- ache, vomiting, stiff neck, and meningeal physical signs, including Kernig’s sign and Brudzinski’s sign. Kernig’s sign is positive when placing a patient’s hips and knees in 90-degree flexion and extending the knee joint elicits pain. Brudzinski’s sign is more sensitive for meningitis and is positive when flexing of the patient’s neck causes flexion of the hips and knees. These signs have long been used to help diagnosis meningitis clinically. As the disease progresses, seizures or coma may occur.
Cutaneous findings include palpable purpura, ecchymosis, widespread macular purpura, and necrosis of the skin with secondary vesiculopustules. The purpura can be angulated with an irregular border. Centrally within the purpuric region, there is often a dusky gray discoloration of the skin. Patients often complain of skin pain. Necrosis may progress to cause gangrene of the digits or distal extremities. In severe cases, entire limbs can become gangrenous. If DIC sets in, the clinical skin findings of DIC may be seen on top of the initial skin findings. The presence of DIC is a poor prognostic indicator.
Fulminant meningococcal septicemia may lead to hemorrhagic necrosis of the adrenal glands; this is termed the Waterhouse-Friderichsen syndrome. It leads ultimately to acute adrenal dysfunction. This syndrome is seen in fewer than 5% of patients with
N. meningitidis septicemia, but it occurs in more than 50% of the fatal cases. Patients present with skin findings of widespread purpura and cyanosis. They have signs and symptoms of hemodynamic collapse, hypotension, acute renal failure, and a biphasic fever. The skin findings are caused by small-vessel embolization or endothelial destruction from the septicemia. Blood extravasates through the damaged endothelial walls and produces massive purpura. The more extensive the cutaneous purpura in meningococcal septicemia, the higher the incidence of Waterhouse-Friderichsen syndrome.
Laboratory testing can be used to diagnosis the disease, but one should not wait for the results to begin therapy if there is a high clinical suspicion of N. meningitidis infection. Culture of N. meningitidis from blood, cerebral spinal fluid (CSF), or tissue is diagnostic. The gram-negative diplococcal bacteria grows on the chocolate agar plate and appears as small, round, moist, gray colonies. Gram staining of CSF shows intracellular gram-negative diplococcal bacteria. This bacteria also grows well on the Thayer-Martin agar plate. The bacteria is oxidase positive and is able to acidify certain sugars. These laboratory data can be used to help differentiate N. meningitidis from other bacteria. CSF samples can be used for polymerase chain reaction (PCR) testing for the bacteria, but this is not routinely done in these cases. All cases of N. meningitidis infection should be reported to state and national health organizations.
Pathogenesis: Meningococcal infections, including septicemia and meningitis, are caused by the gram- negative bacteria, N. meningitidis. This is a diplococcal bacterium that requires an iron source for survival. Because of this unique metabolic requirement, humans are the only known host. The meningococcus bacteria can be found as a transient colonizer in the oropharynx of up to 10% of sampled individuals. These carriers express no sequelae but serve as a potential reservoir for meningococcal disease. The organisms are spread by close contact and sharing of saliva. If the bacteria is able to reproduce to such an extent as to cause bacteremia, it then becomes a potential pathogen. Bacteremia can quickly lead to septicemia (meningococcemia). This is a severe, life-threatening disease that can kill quickly. Meningeal involvement leads to neisserial meningitis. The bacteria exhibit a neurotrophic behavior and attack the lining of the central nervous system.
At least 13 serotypes of N. meningitidis are known, 9 of which have been conclusively shown to cause human disease. Currently, a vaccine is available that protects against the serotypes that most frequently cause disease: serotypes A, C, Y, and W-135. The remaining five serotypes can affect any individual regardless of vaccination status. The bacteria expresses a toxin (lipooligosaccharide) on its surface that causes many of the systemic symptoms of disease. N. meningitidis is an encapsulated bacteria, and this helps protect it from the host’s immune system.
Histology: Most skin biopsy specimens show evidence of vasculitis with neutrophils, fibrinoid necrosis, and extravasated red blood cells. Organisms can be appreciated on tissue Gram stains. Embolism of capillaries and small venules is often seen, and necrosis and ulceration can be secondary findings.
Treatment: Treatment requires prompt recognition of symptoms and immediate intravenous antibiotic therapy. Any close contacts of the patient should be screened for evidence of disease and given prophylactic oral therapy to decrease the potential of an epidemic. The main intravenous antibiotic of choice is ceftriaxone, followed by penicillin or by chloramphenicol in penicillin-allergic patients. Patients with Waterhouse-Friderichsen syndrome need adrenal gland replacement therapy.
Contacts should be treated with ciprofloxacin, rifampin, or ceftriaxone. This prophylactic therapy, as well as intravenous therapy, should be started immediately if clinical suspicion is high enough; delaying therapy for even a few hours to wait for laboratory confirmation can be the difference between life and death.
Immunization is helping to keep the disease incidence low, and guidelines have been established for which high-risk groups should get the vaccine and when. Although the vaccine protects against only 4 of the 13 serotypes of N. meningitidis, it has the potential to decrease the incidence of this disease and save many lives.