Neisseria Meningitidis: Complications of Infection Michael A. Apicella, M.D. Professor of Microbiology and Medicine The University of Iowa, Roy and Lucille J. Carver College of Medicine, Iowa City, IA

Neisseria meningitidis • Gram-negative encapsulated diplococcus • Exclusive human pathogen • Can be a component of the healthy nasopharyngeal microbial flora • Can cause epidemic and endemic infections • Disease occurs in two major age groups – Children below age four and teenagers • Disease in the developed world is primary endemic with rates of 0.5 – 1 case/ 100,000 population • Disease in the developing world is frequently epidemic with case rates as high as 1/1000 population

Neisseria meningitidis • N. meningitidis colonizes the nasopharynx of healthy individuals this is called the “carrier state”. • In non-epidemics (endemic) periods approximately 5% of the population “carries” the organism in the nasopharynx • During epidemics, the carrier rate rises to 30 to 60% • The incidence of meningococcal disease USA today 0.5 per 100,000 - ~fivefold higher in children below age 4 and teenagers Epidemics -1 per 10,000 in developed world -1 per 1000 to 1 per 100 in less-well developed world (all age groups at risk but primary children)

Relationship between age-adjusted case rate and prevalence of serum bactericidal antibody

25

100 90

20

80 70 Percent 60 with 50 bactericidal 40 antibody 30

15

Cases/100,0 00

10

5

20 10

0

1

Goldschneider, 1969, JEM, 129: 1307.

4

10

18

22

30

40

60

N. meningitidis infection • Rapid onset – patient well and six hours later desperately ill. • 40% of the time minimal localizing signs and at times difficult to diagnose. Rule: If suspect - TREAT • Early signs of cutaneous platelet deposition (petechie) require careful dermal and mucosal surface exams. • Evolving disease is complex to manage and patient needs to be in an intensive care unit • Evidence of compartment syndrome, acute renal failure, hemorrhagic diatheses, congestive heat failure, acute respiratory distress syndrome need to be looked for and treated vigorously.

Neisseria meningitidis Virulence factors • Pili (fimbria) - long range attachment fibrils • Opa proteins - short range attachment proteins • Lipopolysaccharide Lipid A - Induces inflammatory response Oligosaccharide - attachment ligand, mimic cell surface human antigens, ICAMs

• Peptidoglycan - Structural integrity and can induce inflammation • porin proteins - Membrane channels for nutrients - can translocate modify host cell membranes and cytoskeleton

and

• Iron uptake proteins - used to acquired iron from human iron binding proteins • Capsular polysaccharide - antiphagcytic factor

N. meningitidis serogroup B membrane Blebs (SEM)

N. meningitidis blebbing in Human Cerebrospinal fluid

Nemark, E et al, Lancet, 360:1741.2002

Meningococcal LPS distributes depending upon the Clinical Syndrome Syndrome

Site

LPS (range ng/L)

Median level ng/L

CSF