Fulminant Meningococcal Sepsis in a Woman With Previously Unknown Hyposplenism

Anita Shah, DO, CPT, MC, USA; Christopher J. Lettieri, MD, MAJ, MC, USA


Medscape J Med. 2008;10(2):36 

In This Article


N meningitidis is a Gram-negative encapsulated dipplococci that was first isolated in 1887. There are 13 serogroups of N meningitidis; however, groups A, B, C, W-135, and Y are the major pathogens involved in causing acute, life-threatening infections.[1] Meningococcal infection remains a leading cause of bacterial meningitis and sepsis in the United States and is a major cause of epidemics in sub-Saharan Africa.[2] Fortunately, this organism is uncommonly encountered, with an incidence of 0.5 to 1.1 cases per 100,000 population. Meningococcus occurs year-round, with a predominance in the winter and early spring. Humans are the only natural reservoir, with the nasopharynx as the site of carriage. N meningitidis colonizes 8% to 25% of healthy individuals. Colonization may be transient, intermittent, or long-term. The prevalence may increase with concomitant viral upper respiratory tract infection, for persons living in crowded living conditions (college students, military recruits, for persons of low socioeconomic status), and with both active and passive smoking.[3] Invasive meningococcal infection occurs most commonly in seronegative persons who have newly acquired N meningitidis.[4]

Risk factors for the development of severe infection include immunocompromised states, complement deficiencies, and asplenism. Absence of protective bactericidal antibodies is the most important predisposing factor for systemic disease. Underlying immune defects such as functional or anatomic asplenia, hyposplenia, deficiency of properdin, or deficiency of terminal complement components (C3 and C5 to C9) confer a predisposition to invasive meningococcal infection. The relative risk of fulminant infection in an asplenic patient is proposed to be 500 times that of persons with an intact spleen.[5] In patients with hyposplenia, the ability to produce antibodies against polysaccharides is diminished and may contribute to the increased risk of infection by encapsulated organisms.[6] However, the exact increase in risk is not well described. Fortunately, infections in such persons account for only a small proportion of N meningitidis cases.[7,8] Complement deficiencies occurring secondary to systemic diseases (systemic lupus erythematosus, multiple myeloma, liver disease, enteropathies, and nephrotic syndrome) can also predispose patients to meningococcal infection.[8]

Manifestations of infection may be abrupt and initially nonspecific. Meningitis secondary to hematogenous spread occurs in about 50% of patients and may present with sudden onset of headache, fever, and neck stiffness. These symptoms may be accompanied by nausea, emesis, and photophobia and may quickly progress to altered mental status.[9] Hallmark features of meningococcemia are fever and petechial rash. This rash develops in 50% to 80% of patients and can be widespread, purpuric, and ecchymotic. It can progress to purpura fulminans, which is often associated with hypotension, acute adrenal hemorrhage, and multiorgan failure.[9] Meningococcemia occurs in 5% to 20% of cases. The causative organism is isolated in more than 75% of these patients.

The clinical diagnosis of meningococcal meningitis relies on the recognition of fever, rash, meningeal signs, and altered mental status, and is confirmed by pleocytosis and Gram stain with or without culture of cerebrospinal fluid (CSF) or blood or skin lesions. Meningococcal meningitis causes a polymorphonuclear leukocytosis in the CSF, which can be evaluated using lumbar puncture.[10] Early diagnosis of meningococcemia can be challenging because the petechial rash may not be present initially.[1] In meningococcemia, Gram-stain results of the CSF are often negative. Blood cultures should be obtained before antibiotic therapy is started, if possible, to aid in the diagnosis.

The cornerstone of treatment in meningococcemia is early detection and rapid administration of antibiotics. Patients with fulminant meningococcemia will require intensive care unit support. Components of therapy include antibiotic therapy, ventilatory support, inotropic support, and intravenous fluids. Corticosteroids should be administered because adrenal hemorrhage and subsequent adrenal insufficiency are common in these patients. In addition, corticosteroids have potent anti-inflammatory effects and have been widely used in patients suspected to have bacterial meningitis.[11] Central venous access is often required and aids in the administration of volume expanders and inotropic drugs. In addition, central venous catheters allow for monitoring of central venous pressures to guide resuscitation. If DIC is present, fresh frozen plasma may be indicated. The use of activated protein C has been approved by the Food and Drug Administration in the treatment of severe sepsis. It is a regulator of coagulation, fibrinolysis, and inflammation and has been found to reduce 28-day all-cause mortality in severe sepsis. A retrospective review of 4360 patients with severe sepsis showed that patients displaying signs and symptoms of purpura fulminans, meningitis, or meningococcal disease who were treated with activated protein C had a similar spontaneous bleeding event rate, a lower observed 28-day mortality rate, and a higher observed rate of intracranial hemorrhage than patients treated with activated protein C who did not display the signs and symptoms of meningococcemia.[12] Treatment should be individualized depending on the severity of hemodynamic compromise. All meningococci in the CSF are killed within 3 to 4 hours, and serum concentrations of the endotoxin fall by 50% after 2 hours of an adequate dose of intravenous antibiotics.[1] Despite this the case fatality rate is approximately 10%. In patients with meningococcemia associated with DIC, the mortality rate is greater than 90%. Substantial sequelae occur in about 11% to 19% of survivors (because of neurologic damage and complications resulting from DIC).[13] Patients with adrenal hemorrhage (Waterhouse-Friderichsen syndrome) have a 55% to 60% mortality rate.[10]

Spread of meningococci occurs through close contact with respiratory secretions, which creates the potential for outbreaks and increases risks to medical staff. Early suspicion, with respiratory isolation for 24 hours after the start of treatment, is essential for protection of all staff.[14] This is paramount and should be done prior to confirmation of infection. Prophylactic antibiotics are recommended for all persons with greater than 8 hours of contact in close proximity (3 feet) of the patient or those who had direct exposure to the patient's oral secretions (face-to-face contact, mouth-to-mouth resuscitation, management of an endotracheal tube, or kissing) within 1 week before the onset of the patient's symptoms until 24 hours after appropriate antimicrobial therapy has been initiated. Chemoprophylaxis can be initiated with rifampin 600 mg twice daily for 2 days, 1 dose of oral ciprofloxacin 500 mg, or 1 intramuscular injection of ceftriaxone 250 mg. Chemoprophylaxis is intended to eradicate any potential colonization by N meningitidis.[3]

Hyposplenia increases a patient's susceptibility to and propensity for fulminant infections from encapsulated organisms such as Streptococcus pneumoniae, Haemophilus influenzae, and N meningitidis. In addition, these patients are susceptible to protozoal infections including malaria and babesiosis.[5] This patient's previously unknown hyposplenism likely contributed to the development of this infection because she was not properly vaccinated and did not have a heightened suspicion for serious illness. She likely had congenital hyposplenia secondary to an immune deficiency. Her only significant medical history was a diagnosis of inflammatory bowel disease. The relationship between inflammatory bowel disease and hyposplenism has been well recognized since 1974; however, the exact mechanism of hyposplenia is poorly understood. The increased level of immune complexes and low level of enteric lymphocytes are believed to contribute to hyposplenia.[15]