Neisseria meningitides

Neisseria meningitides is an aerobic, non-spore-forming Gram-negative coccobacilli that resides in its natural habitat within the nasopharyngeal tract of humans . 5-15% of the human population carries the bacteria in its nonpathogenic form .(a major step in infection is its colonization in the nasophrynx of the human carrier )

Neisseria meningitidis, also simply known as meningococcus is best known for its role in meningitis (meningitis is an inflammation of the membranes that cover the brain and spinal cord). It only infects humans, there is no animal reservoir. It is the only form of bacterial meningitis to cause epidemics.

Strains

There are many strains of meningococcus, clinically the most important are A, B, C and W135:

• A - occurs most often in sub-sahara Africa and vaccination is recommended prior to travel

• B - is the most lethal form, comprising 40% of the cases. The changing nature of the B group has prevented formation of a general B vaccine in the UK..

• C - caused approximately 60% of the cases before the introduction of successful vaccination programme for infants.

• W135 - is particularly a problem for those undergoing annual pilgrimage to Mecca. It is a requirement of Saudi Arabia that all those intending to go on Hajj have a certificate of Men W135 vaccination.

Diseases

• Meningitis

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o Local cytokine release causes brain damage, and systemic cytokine release leads to shock and DIC. Without treatment, the mortality is 85%. In as many as 10-15% of survivors, there are persistent neurological defects, including hearing loss, loss of limbs, paralysis and mental retardation.

o The key feature of meningitis due to N. meningitidis is skin lesions (65%). They start as petechiae, become purpuric and eventually necrotic. The lesions occur as the LOS is shipped out of the cell.

• Meningococcemia alone o Meningococcemia is characterized by a low grade fever, skin lesions

and arthritis developing over a period of days to weeks. • Waterhouse-Friderichsen syndrome

o Waterhouse-Friderichsen syndrome is a syndrome characterized by the bilateral hemorrhagic destruction of the adrenal glands, fulminating DIC and shock.

• Pneumonia- uncommon

Virulence Factors

• The major toxin of N. meningitidis is its lipooligosaccharide,LOS, and its mechanism is endotoxic. The other important determinant of virulence of N. meningitidis is its antiphagocytic polysaccharide capsule.

• Attachment is mediated by fimbriae and possibly by other outer membrane components. Invasion of the mucosal cells occurs by a mechanism similar to that observed with gonococci.

• meningococcal LOS is highly toxic and is lethal for mice and causes a dermal Shwartzman phenomenon (a characteristic type of inflammatory reaction) in rabbits. Meningococcal LOS has been shown to suppress leukotriene B4 synthesis in human polymorphonuclear leukocytes. The loss of leukotriene B4 deprives the leukocytes of a strong chemokinetic and chemotactic factor.

Transmission and Invasion

Transmission is via nasal droplets from asymptomatic carriers. Asymptomatic carriage is found in the nasopharynx in 5-10%. Most of these strains are not pathogenic.

Signs and symptoms of meningococcal disease:

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The symptoms of meningococcal meningitis are high fever, headache and stiff neck; fever and rash are symptoms of meningococcemia. Meningococcemic rash is non-blanching, develops rapidly and usually appears on the armpits, groin, and ankles, and in areas where elastic pressure is applied (like underwear and socks). Other signs and symptoms include nausea, vomiting, weakness, low blood pressure, discomfort looking into bright lights, confusion, sleepiness and, in the extreme, delirium, seizures, and coma. These symptoms usually appear in a range of 2 to 10 days after exposure.

Diagnosis

• Gram stain of CSF • Culture of CSF, blood or skin lesions • N meningitidis is a gram-negative diplococcus that grows well on solid

media supplemented with blood and incubated in a moist atmosphere enriched with carbon dioxide.

• Oxidase and catalase are biochemical markers for preliminary identification of this organism. Sugar fermentations are required for final identification of the species. N meningitidis ferments glucose and maltose, not sucrose or lactose.

• Agglutination reactions with immune serum subdivide the species into serogroups A, B, C, W135, X, Y, and Z, depending on a group-specific capsular polysaccharide antigen.

Immunity and Vaccines

• There is a quadrivalent polysaccharide vaccine that provides protection

against serogroups A, C, Y, and W-135. Currently, it is only required in high risk populations (i.e., military recruits, travelers to Sub-Saharan Africa etc.) The vaccination of college students would be a good idea, although not cost effective for society as a whole.

Treatment

• Treat with a high IV dose of penicillin (PCN) or a cephalosporin if meningococcemia or meningitis.

• Prophylaxis of carriers or those with close exposure with rifampin. (PCN cannot be used because it cannot get into the surface of the uninflammed nasopharyngeal mucosa.)

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Over view of Neisseria and a comparison between pathogenic N. gonorrhoeae and N. meningitidis

Group Characteristics of Neisseria

Neisseria are kidney bean shaped, Gram negative diplococci. Neisseria are oxidase positive. They have cytochrome c oxidase in the electron transport chain, which will oxidize phenylethylene diamine dye to black.

There are 8 species of neisseria, two of which are pathogenic.

Characteristics of the Pathogenic Members (Neisseria gonorrhoeae and Neisseria meningitidis)

Pathogenic Neisseria are obligate human pathogens.

They are fastidious organisms requiring:

• 4-8% CO2 to enhance growth. • Incubation temp. of 30-37oC. Other Neisseria species will grow at 22oC.

They are highly susceptible to heat, cold and drying. They are highly autolytic at stationary phase. They cannot tolerate free fatty acids in media. Media used to culture them include:

o Chocolate agar, which is blood agar that has been heated. The freed hemoglobin binds up the free fatty acids.

o Thayer Martin media, which is chocolate agar plus the following antibiotics, vancomycin (to kill GM+), colistin (to kill other GM-), trimethoprim (a broad spectrum antibiotic), and nystatin (to kill yeasts).

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Comparison between both pathogenic members of Neisseria:

1)Sugar Utilization:

• Patterns of acid production from sugars, such as glucose, maltose, lactose, and sucrose, are used to identify Neisseria and related species. In contrast to most bacteria that produce acid using fermentation, Neisseria spp. produce acid by an oxidative pathway.

2)Mechanism for Invasion of Epithelial Cells: (Deduced from Fallopian Tube Cell Culture with GC)

1. Neisseria stick to mucous secreting but not ciliated cells by their pili and opa proteins. They cause ciliostasis in ciliated cells with LOS and PDG. The endocytosis is directed by porins.

2. The Neisseria are transported through the cells.

3. They are egested into the basement membrane leading to massive inflammation.

4. Ciliated and non-ciliated host cells are destroyed

5. Organisms resist killing by antibody and complement in inflammatory fluids and blood.

6. Attachment to endothelial cells follows.

7. Dissemination of the organisms into the bloodstream (if bacteremia occurs).

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3) Virulence Factors of N. meningitidis (MC) and N. gonorrhoeae (GC)

Iron Binding

• All organisms require an exogenous source of iron. (Review Bacterial Physiology for more information.)

Capsule

Major surface proteins: Pili

Major surface proteins: Porins.

• Porins are very wide channels that allow in a lot of hydrophilic solutes. (Remember Bacterial Structure?)

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Major surface proteins: Target of Blocking Antibody

Major surface proteins: Adherence

Major surface proteins: LOS

• The lipopolysaccharide of Neisseria has a short side chain, and is called lipooligosaccharide or LOS. It is a very potent endotoxin.

Major surface proteins: IgA protease

• An IgA protease can be a handy virulence factor. It cleaves IgA into Fab and Fc fragments. Remember that both S. pneumoniae and H. influenzae had one.

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4) Diagnosis

Epidemiology of Neisseria meningitidis

A

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