Pathogenesis and diagnosis of human meningococcal disease using immunohistochemical and PCR assays

Jeannette Guarner1, Patricia W Greer, Anne Whitney

  • 1Infectious Disease Pathology Activity, Division of Viral Rickettsial Diseases, National Centers for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.

Insights

Fatal sepsis caused by Neisseria meningitidis can be diagnosed and serogrouped using immunohistochemical analysis and PCR on formalin-fixed tissues. These methods reveal meningococcal distribution and pathogenesis in fatal cases.

Area of Science:

  • Infectious Diseases
  • Pathology
  • Microbiology

Background:

  • Neisseria meningitidis is a primary cause of fatal sepsis.
  • Rapid diagnosis is challenging in fulminant cases where cultures are unavailable.

Purpose of the Study:

  • To evaluate immunohistochemical analysis and real-time PCR for diagnosing Neisseria meningitidis in formalin-fixed tissues.
  • To determine the distribution of N. meningitidis and its antigens in fatal and surviving cases.
  • To enable serogroup determination for improved understanding of meningococcal disease.

Main Methods:

  • Immunohistochemical assay applied to formalin-fixed tissue samples from 14 patients.
  • Histopathologic examination of tissues from fatal cases.
  • Real-time PCR for serogroup determination on formalin-fixed samples.

Main Results:

  • Histopathology revealed interstitial pneumonitis, hemorrhagic adrenal glands, myocarditis, meningitis, and thrombi in fatal cases.
  • Immunohistochemistry detected meningococci and antigens within immune cells and extracellularly.
  • PCR successfully serogrouped N. meningitidis in 11 of 14 cases (8 C, 2 Y, 1 B).

Conclusions:

  • Immunohistochemical analysis and PCR are effective for diagnosing and serogrouping N. meningitidis in formalin-fixed tissues.
  • These techniques provide insights into the tissue distribution and pathogenesis of meningococcal disease.
  • Diagnosis is feasible even when cultures are unobtainable in fulminant cases.

Related Concept Videos

Bacterial Meningitis II: Pathophysiology01:26

Bacterial Meningitis II: Pathophysiology

Bacterial meningitis typically begins when pathogens such as Neisseria meningitidis and Streptococcus pneumoniae colonize the nasopharynx and invade the bloodstream. This process is facilitated by bacterial virulence factors, such as polysaccharide capsules, which resist phagocytosis and complement-mediated killing. Less commonly, bacteria reach the central nervous system via contiguous spread from infections like otitis media or sinusitis, through congenital or acquired dural defects, or...
Viral Meningitis01:18

Viral Meningitis

Viral meningitis is the most common form of meningitis and is often referred to as aseptic meningitis to indicate the absence of bacterial involvement. It is generally milder than bacterial meningitis, with symptoms including fever, headache, stiff neck, drowsiness, nausea, photophobia, and vomiting. Rarely, more severe manifestations or death may occur. Common causative agents include enteroviruses, particularly coxsackie A and B viruses and echoviruses, all members of the Enterovirus genus...
Bacterial Meningitis01:24

Bacterial Meningitis

Bacterial meningitis is a severe infectious disease involving inflammation of the meninges, the protective membranes surrounding the brain and spinal cord. It occurs when pathogenic bacteria cross the blood–brain barrier and enter the cerebrospinal fluid. Common causative organisms include Neisseria meningitidis, Streptococcus pneumoniae, Haemophilus influenzae type b, Listeria monocytogenes, and Escherichia coli K1. The exact route of entry varies by pathogen and host condition.Routes of Entry...
Rapid Identification of Pathogens01:25

Rapid Identification of Pathogens

MALDI-TOF MS has transformed clinical microbiology by offering a rapid and reliable method for pathogen identification. The traditional approach to microbial identification typically involves time-consuming culture techniques and biochemical tests, which can delay the initiation of appropriate antimicrobial therapy. MALDI-TOF MS avoids these delays by using characteristic ribosomal protein mass patterns of microbial cells, enabling accurate species-level identification within minutes.Principle...
Bacterial Meningitis I: Introduction01:22

Bacterial Meningitis I: Introduction

Bacterial meningitis is a severe, life-threatening inflammation of the meninges, particularly the pia mater and arachnoid mater, affecting the subarachnoid space, ventricles, and cerebrospinal fluid (CSF). If untreated, it can lead to significant neurological complications or death.Causative AgentsCommon pathogens vary with age and immune status. In adults, major organisms include Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae. Streptococcus agalactiae (group B...