Meningococcemia

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Cafer Zorkun, M.D., Ph.D. [2]

Synonyms and related keywords: meningococcal infections, epidemic cerebrospinal fever, Waterhouse-Friderichsen syndrome, meningitis, meningococci, fulminant meningococcemia, acute meningococcemia, meningococcemia, meningococcal meningitis, bacterial meningitis, meningococcal disease, Neisseria meningitidis, N meningitidis, chronic meningococcemia

Overview

Meningococcemia is the presence of Neisseria meningitidis (also known as meningococcus), a severe bacterical infection, in the blood stream. It is demonstrated by blood culture. The disease is hard to identify as it can appear in several different forms, depending on which part of the body the bacteria invade. Neisseria meningitides is a gram-negative diplococcus. The bacteria is known to cause meningitis, septicaemia, pneumonia, and even rarely urethritis.

Most cases of meningococcal meningitis occur in children. Early recognition and treatment of anyone exposed to meningococcus is extremely important to prevent serious illness or death. In cases of serious infection, sufferers may have to have limbs amputated as infected flesh dies off and may otherwise spread gangrene.

Epidemiology and Demographics

• Case rate is 1-2 per 100,000 in the US in 1980. More recently, there are approximately 2,500 cases of meningococcal infections per year in the United States.
• Since the introduction of Haemophilus influenzae type b vaccine in 1990 for infants the majority of cases of bacterial meningitis have been in adults; historically 45-87% of cases have been in children.
• Second most common cause of community-acquired adult bacterial meningitis after pneumococcus.
• In West African countries during 1996-1997 there were 213,658 cases and 21,830 deaths due to menigococcal disease.

Risk Factors

• Episodic epidemic nature of meningococcal meningitis particularly among young children and military recruits was known since the 18th century.
• Epidemics occur generally among poorest groups where crowding and lack of sanitation are common.

Pathophysiology & Etiology

• Transmission through respiratory secretions from a nasopharyngeal carrier case-patient.
• Shock is due to lipooligosaccharide which is a potent toxin. This toxin initiates release of inflammatory cytokines, reactive oxygen radicals, prostaglandins, arachidonic acid, complement activated products, platelet aggregating factor, and perhaps nitric oxide.

Molecular Biology

• The polysaccharide capsule is the basis of the serogroup typing system.
• 13 Serotypes are described based on capsular polysaccharide: A, B, C, D, X, Y, Z, E, W-135, H, I, K, and L.
• Serogroup A usually with epidemics in less developed nations and an attack rate of as high as 500 cases per 100,000 population.
• Serogroup B usually in developed nations with attack rate of 50-100 cases per 100,000 population.
• Serogroup C usually in both developed and less developed populations and an attack rate of up to 500 per 100,000 population.

Natural History

• Before antibiotics the case fatality rate was over 50%, particularly dangerous in infants and elderly (84% and 72% respectively). Now it is often as low as 8% in major medical centers.

Diagnosis

One of Four Scenarios is Often Present

1. Bacteremia without sepsis. Admission for upper respiratory illness or viral exanthem. Positive blood cultures for Neisseria meningitides.
2. Meningococcemia without meningitis. Septic patient with leukocytosis, skin rashes, generalized malaise, weakness, headache, and hypotension on admission or shortly after.
3. Meningitis with or without meningococcemia. Patients with headache, fever, meningeal signs and cloudy spinal fluid. No pathologic reflexes.
4. Meningoencephalitic presentation. Profoundly obtunded with meningeal signs and septic spinal fluid. Altered reflexes (either absent or rarely hyperactive). Pathologic reflexes are often present.

General Symptoms

According to research, these are typical symptoms of infection. Not all of these symptoms will appear, and not necessarily in this order. Every child with purpuric rash and high fever should be treated as meningococcemia - until proven otherwise.

• Rash, pinpoint red spots (petechiae)
• High fever
• Severe headache
• Severe malaise
• Nausea and vomiting
• Stiff neck
• Sensitivity to light (photophobia)
• Mental status changes
• Headache, confusion, and stiff neck occurred as symptoms in less than half of 53 patient in one series by Carpenter and Petersdorf.
• Patient may complain of significant myalgias.

HUSSEIN AND SHAFRAN CANADIAN REVIEW OF BACTERIAL MENINGITIS

Fever >= 37.7 degrees Celsius	97%
Nucal Rigidity	87%
Headache	66%
Denied Headache	16%
Nausea/Vomiting	55%
Confusion	56%
Decreased Consciousness	51%
Focal Neurologic Deficits	23%
Seizure	29%

Physical Examination

• Fever
• Not infrequently hypotension and shock

Skin

• Petechial rash manifesting as discrete lesions 1-2 mm in diameter frequently on the trunk and lower portions of the body.
• Petechial regions can coalesce and form larger lesions that appear ecchymotic.
• A rash may appear that mimics a viral exanthem, particularly rubella. Not purpuric and non-pruritis and is transient, generally not lasting more than 2 days and is frequently gone hours after first observation.

Eyes

• Palpebral and ocular conjunctival petechia.

Heart

• Congestive heart failure, myocarditis, pericarditis may be present

Lungs

Rales may be present, consolidation may be present if pneumonia is present

Neurologic

Nuchal rigidity and seizures may be present

Laboratory Findings

Electrolyte and Biomarker Studies

• Blood cultures were positive in 41.4% of 400 cultures in one series of patients with meningococcal disease.
• Cerebrospinal fluid (CSF) culture and gram stain were positive in 94% of patients in the same series.
• The ability to culture the meningococcus from CSF will not be substantially reduced if the cultures are obtained within one hour of antibiotic administration.
• One series revealed a median leukocyte count of approximately 1200 in CSF (range 10 to 65,000/mm). Approximately 75% had a CSF glucose level less than 40 mg/100 mL. CSF protein ranged from 25 to over 800 mg/100 mL with a median value of 150 mg/100 mL.
• Polymerase chain reaction (PCR) has been shown in a study with 54 samples to be 91% sensitive and specific, particularly useful when cultures may be negative due to prior antibiotic administration.
• Latex agglutination can detect A, B, C, Y, and W-135 though the sensitivity of detecting serogroup B is low.

HUSSEIN AND SHAFRAN CANADIAN REVIEW OF BACTERIAL MENINGITIS

Cloudy CSF	78%
CSF >= 1000 WBC/mm3	56%
CSF >= 10,000 WBC/mm3	14%
CSF Neutrophil predominance	90%
CSF Glucose =< 50 mg/deL	70%
CSF Protein > 200 mg/dL	66%
Gram Stain without bacteria	53%
Gram Stain Neg --> Culture Pos	47%

Treatment

Acute Pharmacotherapies

• Cephalosporin CSF penetration: cefuroxime 11-14 %; ceftriaxone 1.5-7%, cefotaxime 4-54%, and ceftazidime 14%.
• Ceftriaxone CSF half life approximately 5 hours.
• Potential antibiotics include cephalosporins, penicillin, and chloramphenicol.
• Therapy may be as brief as 10 to 14 days in fully sensitive organisms.
• Steroid use particularly in purpura fulminans and adrenal hemorrhage (Waterhouse-Friderichsen syndrome) is controversial.

Prophylaxis

• Rifampin 600 mg PO q12h x 4 doses total or alternatively ciprofloxacin 500 mg PO x 1 in patients over 18 who cannot tolerate rifampin

Risk Stratification and Prognosis

• Current vaccines have polysaccharides of groups A, C, Y, and W-135. No vaccine available presently for group B disease since the polysaccharide is not sufficiently immunogenic to produce a reliable antibody response in humans to be effective.
• Rates of meningococcus in US college students as a whole 0.7 per 100,000.
• Rates of meningococcus in US persons aged 18-23 not in college 1.5 per 100,000.
• Rates of freshmen living in dormitories 4.6 per 100,000.
• Rates for college students in UK 13.2 per 100,000 versus those not in college of 5.5 per 100,000.

Prevention

The most important form of prevention is a vaccine against Neisseria meningitidis. Different countries have different strains of the bacteria and therefore use different vaccines. Five serogroups, A, B, C, Y and W135 are responsible for virtually all cases of the disease in humans. Vaccines are currently available against four of the five strains, and a vaccine against the B strain is in development. Menactra and Menomune are two commonly used vaccines. Unfortunately, there is currently no evidence that any of the current vaccines offer significant protection beyond three years.

Additionally, basic hygiene measures, such as hand washing and not sharing drinking cups, can reduce the incidence of infection by limiting exposure.

When a case is confirmed, all close contacts with the infected person can be offered antibiotics to reduce the likelihood of the infection spreading to other people.

Related chapters

• Endocarditis
• Meningitis
• Waterhouse-Friderichsen syndrome

Resources

• Template:FPnotebook
• Template:DermAtlas
• www.meningococcal.com.au
• Medline Plus

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