Neisseria meningitidis: Infectious substances pathogen safety data sheet

For more information on Neisseria Meningitidis, see the following:

• Invasive Meningococcal Disease - Canada.ca
• Meningococcal vaccines: Canadian Immunization Guide - Canada.ca

Section I – Infectious agent

Name

Neisseria meningitidis

Agent type

Bacteria

Taxonomy

Family

Neisseriaceae

Genus

Neisseria

Species

meningitidis

Synonym or cross-reference

Meningococci^{Footnote 1}, meningococcemia, meningococcal infection, meningococcal meningitis.

Characteristics

Brief description

Neisseria meningitidis belongs to the family Neisseriaceae^{Footnote 2}. It is a Gram-negative, non-spore forming, non-motile, encapsulated, and non acid-fast diplococci and appears in kidney bean shape under the microscope^{Footnote 1Footnote 3}. The 2.3 mbp N. meningitidis genome has a G+C content of 51.5% and contains 2158 open reading frames^{Footnote 4}. N. meningitidis requires an aerobic environment with 5% CO₂ and enriched media containing blood for growth^{Footnote 1}. Medium-sized, smooth, transparent, non-pigmented, non-hemolytic, and convex colonies are produced on blood agar after overnight incubation at 35-37°C^{Footnote 1}. There are at least 13 serogroups, with serogroups A, B, C, X, W135, and Y being the most commonly encountered from invasive disease cases^{Footnote 5}.

Properties

In humans, N. meningitidis colonizes the nasopharynx and is often non-pathogenic and commensal^{Footnote 6}. To cause serious disease and meningitis, the bacteria must survive in the bloodstream, pass through the blood-brain-barrier (BBB) to enter and infect the central nervous system (CNS). A number of virulence factors are involved such as the polysaccharide capsule, pili and adhesins that play a role in its survival in the bloodstream and travels through the BBB. Factor H-binding protein aids in evading the host immune system through its interaction with factor H. The polysaccharide capsule is the most important virulence factor as it also is involved in adhesion to and invasion of CNS tissues. Adherence is further aided by Opa and Opc proteins. These proteins, along with Neisseria adhesin A and focal adhesion kinase, also play a role in the invasion of host CNS^{Footnote 6}.

Section II – Hazard identification

Pathogenicity and toxicity

N. meningitidis has a wide range of clinical manifestations, ranging from transient mild sore throat to fatal meningitis or meningococcal septicemia^{Footnote 3}. Meningitis and septicemia are the most common presentations of the disease. The carrier state is the most common form of meningococcal infection, with colonization occurring in approximately 10% of healthy people^{Footnote 7Footnote 8}. Individuals may remain a carrier for up to 6 months after infection^{Footnote 5}. In some carriers, the bacteria enters the blood or meninges which results in invasive meningococcal disease. The onset of symptoms usually occur between 2 to 10 days after exposure^{Footnote 5}. Disease caused by N. meningitidis present in a number of ways.

Transient meningococcemia: Patients present with mild flu-like symptoms such as fever, joint pain, and occasionally rash. The illness lasts for a few days or weeks^{Footnote 3}.

Meningitis^{Footnote 1Footnote 2Footnote 3}: Most patients present with signs of meningeal irritation, including, neck stiffness, bulging fontanelle (in infants), irritability, lying on one side away from light, and inability to extend the knee when hip is flexed in supine position (positive Kernig's sign)^{Footnote 3}. Convulsions, declining level of consciousness, and coma may occur. The petechial rash of meningococcemia may also occur^{Footnote 1}.

Meningococcemia: Patients present with rapid onset of fever, vomiting, photophobia, convulsions, skin rash, lethargy, irritability, drowsiness, diarrhea, muscular pain, arthralgia, and rarely, acute abdominal pain^{Footnote 3}. The characteristic meningococcal rash is due to disseminated intravascular coagulation, caused by meningococcal bacteremia, and can result in loss of digits and limbs in some cases^{Footnote 1Footnote 3}. In severe cases, patients may present with septic shock, leading to respiratory failure, renal failure, coma, and even death within 24 hrs of onset of symptoms^{Footnote 3}.

Chronic meningococcal disease: Rare manifestation of N. meningitidis infection^{Footnote 3}. Patients present with chronic intermittent high fever, joint pain, and headache, with or without skin lesions.

Other more rare manifestations of N. meningitidis infection include septic arthritis; upper or lower respiratory tract infections such as otitis media, pharyngitis, bronchitis, and pneumonia; pericarditis; myocarditis; endocarditis; and conjunctivitis^{Footnote 3}.

Epidemiology

The incidence of meningococcal disease is estimated at 1.2 million cases per year with about 135,000 deaths, with the highest incidence of disease in infants less than 1 year old (5.38 cases per 100,000) ^{Footnote 9}. Although there are at least 13 serogroups of N. meningitidis, 90% of meningococcal disease worldwide is caused by the serogroups A, B, C, W135, X and Y^{Footnote 5}.

The highest incidence, with large epidemic outbreaks, has been reported for the serogroup A, in the 'Meningitis Belt' region of sub-Saharan Africa, affecting approximately 1,000 per 100,000 population^{Footnote 10}. In the United States, serogroups B, C, and Y are responsible for disease in children and young adults^{Footnote 5Footnote 11}, with an incidence of 0.5–1.1 cases per 100,000 population, or approximately 1,400–2,800 cases per year, with the highest rates in infants, and a second peak in adolescence and early adulthood.

Between 2006 and 2011, an average of 196 cases were reported annually in Canada, with an average incidence of 0.58 cases per 100,000 population^{Footnote 12}. During this time period, incidence rates were highest among infants less than one year of age (average 7.35 cases per 100,000), followed by 1 to 4 year olds (1.89), and 15 to 19 year olds (1.17). In Canada, serogroups B, C, W135 and Y are the most commonly reported serogroups^{Footnote 12}. Between 2006 and 2011, incidence rates of serogroup B were highest (0.33 cases per 100,000) for all meningococcal isolates.

With the introduction of meningococcal C immunization programs, not unexpectedly, the incidence of serogroup C has decreased significantly from 0.13 in 2006 to 0.01 cases per 100,000 in 2011^{Footnote 12}.While the incidence of serogroup B remains predominant, diseases of serogroup W135 and Y have stabilized at relatively lower incidence rates of 0.03 (range: 0.02 to 0.04) and 0.10 (range: 0.08-0.11) cases per 100,000, respectively^{Footnote 12}.

An outbreak of disease due to N. meningitidis serogroup W135 occurred in 2000 and 2001 among pilgrims returning from the annual Islamic pilgrimage to Saudi Arabia (the Hajj) and their contacts. The first year, the attack rate of W135 disease was 25 cases per 100,000 pilgrims. In Singapore, after the introduction of a quadrivalent meningococcal vaccine for the Hajj in 2001, no pilgrim from this country developed W135 disease. However, as the estimated attack rates for household contacts of returning pilgrims increased from 18 cases to 28 cases per 100,000 contacts for the years 2000 and 2001, it is evident that carriage was still possible^{Footnote 13}.

Host range

Natural host(s)

Humans^{Footnote 1Footnote 5}.

Other host(s)

None

Infectious dose

Unknown

Incubation period

2-10 days (average 2-4 days)^{Footnote 3}; invasive infections occur within 14 days after initial infection.

Communicability

Highly contagious^{Footnote 1}. Person-to-person transmission occurs through droplets shed from the upper respiratory tract or direct contact with oropharyngeal secretions through sharing of drinks or intimate kissing; transfer via contaminated fomites has been postulated but is considered rare^{Footnote 5Footnote 13}. An individual remains infectious as long as meningococci are present in respiratory/oral secretions.

Section III – Dissemination

Reservoir

Humans^{Footnote 1}.

Zoonosis

None

Vectors

None

Section IV – Stability and viability

Drug susceptibility/resistance

Susceptible to rifampicin, penicillin G, sulfonamides, and broad spectrum cephalosporins such as ceftriaxone and cefotaxime^{Footnote 2}. Strains resistant to penicillin, sulfonamides, rifampicin, tetracyclines, and broad spectrum cephalosporins have been isolated^{Footnote 14}. Strains resistant to chloramphenicol have been reported in Vietnam and France^{Footnote 2}.

Susceptibility to disinfectants

N. meningitidis is highly susceptible to common disinfectants^{Footnote 15}. Common disinfectants used against vegetative bacteria include 1% sodium hypochlorite, 70% ethanol, phenolics, 2% glutaraldehyde, formaldehyde, and peracetic acid^{Footnote 16}.

Physical inactivation

N. meningitidis is readily inactivated by low temperatures^{Footnote 10}. It can also be inactivated by exposure to 65°C for 5 minutes or 80°C for 2 minutes, or drying for a few hours at 20°C. Most vegetative bacteria can also be inactivated by moist heat (121°C for 15 minutes- 30 minutes) and dry heat (160-170°C for 1-2 hours)^{Footnote 17}.

Survival outside host

N. meningitidis has been reported to survive on glass and plastic and cloth at ambient temperatures for hours to days (up to 8 days)^{Footnote 18Footnote 19}.

Section V – First aid/medical

Surveillance

Monitor for symptoms. Culture of clinical specimens from a sterile site on blood agar with stain test can be used for diagnosis. Other methods include polymerase chain reaction (PCR), antigen detection and enzyme-linked immunosorbent assay (ELISA)^{Footnote 1Footnote 2Footnote 3}. Serotyping and multi-locus sequencing typing can be done through multi-plex PCR and genomic sequencing^{Footnote 5Footnote 10}.

Note: The specific recommendations for surveillance in the laboratory should come from the medical surveillance program, which is based on a local risk assessment of the pathogens and activities being undertaken, as well as an overarching risk assessment of the biosafety program as a whole. More information on medical surveillance is available in the Canadian Biosafety Handbook.

First aid/treatment

As meningococcal meningitis can present similarly to other bacterial meningitides, treatment with antibiotics should be initiated as soon as possible^{Footnote 10}. Treatment with a 7 day course of intravenous or intramuscular with a third-generation cephalosporin such as ceftriaxone or cefotaxime is recommended^{Footnote 3Footnote 5}. If the organism is found to be susceptible to penicillin treatment may be switched to penicillin-G^{Footnote 8}. Other antibiotics used for treatment of meningococcal diseases include chloramphenicol, fluoroquinolones, and meropenem.

Note: The specific recommendations for first aid/treatment in the laboratory should come from the post-exposure response plan, which is developed as part of the medical surveillance program. More information on the post-exposure response plan can be found in the Canadian Biosafety Handbook.

Immunization

Monovalent conjugate meningococcal vaccines (Men-C-C) and Quadrivalent conjugate meningococcal vaccines (Men-C-ACYW), have been developed and are available for use in Canada^{Footnote 20}.

For high risk individuals such as those with underlying medical conditions and those who are at increased risk of exposure to meningococcal disease, Men-C-ACYW are recommended. However, depending on the specific underlying condition or risk of exposure, recommended vaccination may vary and the Canadian Immunization Guide should be followed^{Footnote 14}.

Serogroup B vaccines (Trumenba^® and BEXSERO) and quadrivalent conjugate vaccines Men-C-ACYW-TT (NIMENRIX^® and MenQuadfi™) for meningococcal disease are currently under review by the National Advisory Committee on Immunization (NACI)^{Footnote 14}.

Note: More information on the medical surveillance program can be found in the Canadian Biosafety Handbook, and by consulting the Canadian Immunization Guide.

Prophylaxis

Chemoprophylaxis is recommended for close contacts of patients with meningococcal disease, such as individuals exposed to an infected household member, daycare, or nursery school contact or anyone exposed to oral secretions from infected person^{Footnote 3}. Chemoprophylaxis should be given within 24 hours of diagnosis of the disease. Antibiotics used for chemoprophylaxis include oral rifampicin, oral ciprofloxacin, and intramuscular ceftriaxone^{Footnote 5Footnote 8Footnote 21}.

Note: More information on prophylaxis as part of the medical surveillance program can be found in the Canadian Biosafety Handbook.

Section VI – Laboratory hazard

Laboratory-acquired infections

At least 8 incidents of infection among laboratory workers with at least one death have been reported previous to 1974^{Footnote 22Footnote 23Footnote 24}. Two fatal cases were reported in 1988^{Footnote 25} and a more recent case was reported in 2012, resulting in death to the development of serogroup B meningococcal disease^{Footnote 26}.

Note: Please consult the Canadian Biosafety Standard (CBS) and Canadian Biosafety Handbook for additional details on requirements for reporting exposure incidents.

Sources/specimens

Pharyngeal exudates, cerebrospinal fluid, blood, nasopharyngeal and oropharyngeal swabs, bronchoalveolar lavage, biopsy specimens, and saliva^{Footnote 2Footnote 3}.

Primary hazards

Accidental parenteral inoculation, exposure of mucous membranes to infectious droplet, nuclei or aerosols, and ingestion^{Footnote 2Footnote 3}.

Special hazards

None

Section VII – Exposure controls/personal protection

Risk group classification

Neisseria meningitidis is a Risk Group 2 Human Pathogen^{Footnote 27}.

Containment requirements

Containment Level 2 facilities, equipment, and operational practices outlined in the Canadian Biosafety Standard for work involving infectious or potentially infectious materials, animals, or cultures.

Protective clothing

The applicable Containment Level 2 requirements for personal protective equipment and clothing outlined in the Canadian Biosafety Standard are to be followed. The personal protective equipment could include the use of a lab coat and dedicated footwear (e.g., boots, shoes) or additional protective footwear (e.g., boot or shoe covers) where floors may be contaminated (e.g., animal cubicles, post mortem rooms), gloves when direct skin contact with infected materials or animals is unavoidable, and eye protection where there is a known or potential risk of exposure to splashes.

Note: A local risk assessment will identify the appropriate hand, foot, head, body, eye/face, and respiratory protection, and the personal protective equipment requirements for the containment zone and work activities must be documented.

Other precautions

The transmissibility (by direct contact with infectious respiratory droplets or oral secretions) of N. meningitidis justifies the use of a BSC or other primary containment devices for activities with open vessel; centrifugation to be carried out in sealed safety cups or rotors that are unloaded using a mechanism that prevents their release. Respiratory protection to be considered when BSC or other primary containment devices cannot be used; inward airflow is required for work involving large animals or large scale activities.

Use of needles and syringes are to be strictly limited. Bending, shearing, re-capping, or removing needles from syringes to be avoided, and if necessary, performed only as specified in standard operating procedures (SOPs). Additional precautions are required with work involving animals or large-scale activities.

For diagnostic laboratories handling primary specimens that may contain Neisseria meningitidis, the following resources may be consulted:

• Human Diagnostic Activities Biosafety Guideline
• Local Risk Assessment Biosafety Guideline

Section VIII – Handling and storage

Spills

Allow aerosols to settle. Wearing personal protective equipment, gently cover the spill with absorbent paper towel and apply suitable disinfectant, starting at the perimeter and working towards the centre. Allow sufficient contact time with the disinfectant before clean up (Canadian Biosafety Handbook).

Disposal

All materials/substances that have come in contact with the regulated materials to be completely decontaminated before they are removed from the containment zone or standard operating procedures (SOPs) to be in place to safely and securely move or transport waste out of the containment zone to a designated decontamination area / third party. This can be achieved by using decontamination technologies and processes that have been demonstrated to be effective against the regulated material, such as chemical disinfectants, autoclaving, irradiation, incineration, an effluent treatment system, or gaseous decontamination (Canadian Biosafety Handbook).

Storage

The applicable Containment Level 2 requirements for storage outlined in the Canadian Biosafety Standard are to be followed. Primary containers of regulated materials removed from the containment zone to be labelled, leakproof, impact resistant, and kept either in locked storage equipment or within an area with limited access.

Section IX – Regulatory and other information

Canadian regulatory information

Controlled activities with Neisseria Meningitidis require a Pathogen and Toxin licence issued by the Public Health Agency of Canada.

The following is a non-exhaustive list of applicable designations, regulations, or legislations:

• Human Pathogens and Toxins Act and Human Pathogens and Toxins Regulations
• Quarantine Act
• National notifiable disease

Last file update

April, 2024

Prepared by

Centre for Biosecurity, Public Health Agency of Canada.

Disclaimer

The scientific information, opinions, and recommendations contained in this Pathogen Safety Data Sheet have been developed based on or compiled from trusted sources available at the time of publication. Newly discovered hazards are frequent and this information may not be completely up to date. The Government of Canada accepts no responsibility for the accuracy, sufficiency, or reliability or for any loss or injury resulting from the use of the information.

Persons in Canada are responsible for complying with the relevant laws, including regulations, guidelines and standards applicable to the import, transport, and use of pathogens in Canada set by relevant regulatory authorities, including the Public Health Agency of Canada, Health Canada, Canadian Food Inspection Agency, Environment and Climate Change Canada, and Transport Canada. The risk classification and related regulatory requirements referenced in this Pathogen Safety Data Sheet, such as those found in the Canadian Biosafety Standard, may be incomplete and are specific to the Canadian context. Other jurisdictions will have their own requirements.

Copyright ^© Public Health Agency of Canada, 2024, Canada