—  SPECIALTY CONFERENCE  —

Infectious Disease Pathology

Case 2 - Meningococcemia

Jeannette Guarner
Center for Disease Control
Atlanta, Georgia


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Clinical History:
A 21 year-old woman presented to the emergency room with sudden onset of fever, chills, and abdominal pain. The patient died shortly after arriving. The person accompanying the patient commented that she had had diarrhea the day before. The patient had been living in Oklahoma but had immigrated from Mexico 6 months earlier. During the autopsy, no macroscopic abnormalities were observed except for fine petechia in the conjunctiva. Microscopic exam of the heart showed focal areas of inflammation and the pathologist sent the case to CDC for Chagas' disease testing.

Diagnosis: Meningococcemia


Case 2 - Figure A
Case 2 - Figure B

Histologic findings
H&E: Small, scattered, interstitial hemorrhages were noted in the myocardium. Focally, myocytes were surrounded by inflammatory cells, and small capillaries showed extravasation of neutrophils accompanied by what appeared to be bacteria.

Additional testing
Tissue Gram stain: Clusters of Gram-negative cocci were noted inside blood vessels.

Immunohistochemistry for Neisseria meningitidis: Positive staining of cocci inside inflammatory cells and extracellularly in blood vessels. Granular antigens were observed inside phagocytic cells.

Discussion

Myocarditis
Postmortem studies have shown that myocarditis is a major cause of sudden, unexpected death in children and adults less than 40 years of age.

The current definition of myocarditis is based on histopathologic criteria known as the Dallas criteria. Diagnosis of active myocarditis includes infiltrating lymphocytes and myocytolysis.

The Dallas criteria were developed to help establish diagnosis of myocarditis in endomyocardial biopsies. By using the Dallas criteria myocarditis can be classified into:

  1. definitive,
  2. borderline,
  3. persistent (ongoing), and
  4. healing (resolving) myocarditis.

Diagnostic problems when using the Dallas criteria occur because of interobserver variability when interpreting histopathologic features in biopsy samples, potential discordance between clinical and histologic diagnosis, and the focal nature of myocarditis.

A number of systemic diseases can be accompanied by myocardial inflammation. There are also infectious and toxic agents that have particular tropism for heart muscle and cause myocarditis. According to Feldman and McNamara the most frequent causes of myocardial inflammation include: infections (coxsackievirus and HIV), immune-mediated autoantigens (Chagas' disease, sarcoidosis, scleroderma, and systemic lupus erythematosis), and toxic (anthracyclines and ethanol).

Detection of infectious agents in heart tissue specimens of patients with myocarditis has not been consistent. Causes:

  1. The specimen is obtained after the infection has been cleared.
  2. The myocarditis may be due to an immune-mediated phenomenon where the inflammatory infiltrate appeared after the infectious agent or another pathologic phenomenon uncovered autoantigens (examples: sarcoidosis and Chagas' disease).
  3. Detection level of assays used is not sensitive enough to identify small numbers of microorganisms.
The most common infectious agent causing myocarditis worldwide is T. cruzi. Chagasic myocarditis occurs years or even decades after the acute infection has taken place. Chronic Chagas' disease can be diagnosed serologically (complement fixation, hemagglutination, indirect fluorescence and ELISA). Patients with Chagas' myocarditis can present with a variety of heart symptoms including chest pain, congestive heart failure, syncope, and sudden death. Pathologically, there is cardiomegaly and an apical heart wall aneurysm can be observed. Microscopically there is patchy myocarditis accompanied by various degrees of fibrosis. Pseudocysts of T. cruzi amastigotes can be difficult or impossible to find. Chagasic myocarditis has been attributed to an autoimmune phenomenon; however, on a previous study we demonstrated that inflammation was associated with persistent T. cruzi antigens.

Bacterial causes of myocarditis include: brucella, Corynebacterium diphtheriae, gonococcus, Haemphilus influenzae, meningococcus, mycobacterium, Mycoplasma pneumoniae, pneumococcus, salmonella, Serratia marcescens, staphylococcus, Streptococcus pyogenes, Treponema pallidum, Tropheryma whippelii, Vibrio cholerae, borrelia, leptospira, Coxiella burnetii, Rickettsia rickettsii, Rickettsia tsutsugamushi.

Meningococcal disease
Worldwide, Neisseria meningitidis remains the leading cause of bacterial meningitis and fatal sepsis. The severity of symptoms and rapid clinical deterioration of individuals with meningococcal disease requires immediate empirical therapy based on clinical suspicion and epidemiological information. Definitive diagnosis of N. meningitidis on the index case is important for prophylaxis of household and other contacts.

Classic laboratory diagnosis has relied on culture of N. meningitidis from a sterile site (blood and/or cerebrospinal fluid). However, sensitivity of culture may be low, especially if it is performed after initiation of antibiotics, thus alternative diagnostic methods using a variety of tissues and techniques such as antigen detection (latex agglutination), and polymerase chain reaction (PCR) have been developed.

N. meningitidis colonizes the naso-oropharygeal mucosa in up to 37% of young adults (15 to 24 years old) and rarely causes disease. Bacteremic meningococcal disease, septicemia with shock and meningitis occur only when the bacteria can attach and invade the respiratory epithelium, and enter the circulation evading bactericidal activity.

In-vitro studies have shown that different membrane components of N. meningitidis induce monocytes and neutrophils to produce proinflammatory cytokines (tumor necrosis factor-alpha, IL-1, IL-6, interferon-gamma, and others). In-vivo, these cytokines play an important role in causing shock, inducing an inflammatory response, and causing disseminated intravascular coagulation (DIC).

Pathology attributed to DIC in meningococcemia:

  • hemorrhage of adrenal glands (Waterhouse-Friderichsen syndrome),
  • thrombi in glomeruli, and
  • skin purpuric lesions.
Pathology attributed to host inflammatory reaction in meningococcal disease:
  • acute suppurative leptomeningitis,
  • myocarditis,
  • pneumonitis/ pneumonia,
  • skin with vasculitis,
  • splenitis, and
  • non-specific hepatitis.
Some authors have demonstrated that patients with meningococcal meningitis have higher concentrations of endotoxins and cytokines in the CSF compared to those found in the blood. They have also shown positive cultures from the CSF but rarely from the blood.

Incidence of meningococcemia is highest in school children, adolescents, and young adults. Transmission is by direct contact with contaminated respiratory secretions or airborne droplets. Laboratory acquisition of meningococcal disease has been documented.

Prevention of spread is based on vaccination and chemoprophylaxis of close contacts. Treatment of patients is with intravenous penicillin has decreased mortality dramatically.

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