Aggregatibacter actinomycetemcomitans: Infectious substances pathogen safety data sheet 

Section I - Infectious agent

Name

Aggregatibacter actinomycetemcomitans

Agent type

Bacteria

Taxonomy

Family

Pasteurellaceae

Genus

Aggregatibacter

Species

actinomycetemcomitans

Synonym or cross - reference

Formerly Actinobacillus actinomycetemcomitans, Haemophilus actinomycetemcomitans, Bacterium actinomycetemcomitans^{Footnote 1Footnote 2}.

Characteristics

Brief description

Aggregatibacter actinomycetemcomitans is a Gram-negative, catalase-positive, nonmotile coccobacillus measuring approximately 0.4 x 0.1 μm^{Footnote 1}. Fimbriae may occur in a peritrichous array, measuring more than 2 µm in diameter, and in bundles, forming colonies with a star-shaped interior (star-positive), or star-negative colonies in the case of nonfimbriated strains^{Footnote 1Footnote 3}. Seven serotypes (a-g) have been identified based on the surface polysaccharide located on the O-side chain^{Footnote 4}. The genome of model strain IDH781 is approximately 2.2 Mbp in size with a G+C content of 44.3%, consistent with other strains^{Footnote 5}.

Properties

A. actinomycetemcomitans is a fastidious facultative anaerobe that grows well in microaerophilic environments with 5-10% CO₂^{Footnote 6}. Mature colonies form on chocolate agar in 2-3 days^{Footnote 7}. A. actinomycetemcomitans are commensal bacteria of the human oral cavity; they inhabit dental plaque and oral biofilm. Adhesin proteins aid in binding to surfaces in the oral cavity^{Footnote 8}. Virulence factors produced by A. actinomycetemcomitans include leukotoxin (LtxA), epitheliotoxin, bacteriocin, collagenase, and a cytolethal distending toxin (Cdt)^{Footnote 9}. Virulence potential varies among strains; strain JP2 is highly leukotoxic^{Footnote 10}. Immunosuppressive proteins secreted by A. actinomycetemcomitans inhibits DNA, RNA, protein, IgG, and IgM synthesis in human lymphocytes and inhibits B and T cell responses to mitogens^{Footnote 4}.

Section II - Hazard identification

Pathogenicity and toxicity

A. actinomycetemcomitans is the major causative agent of localized aggressive periodontitis^{Footnote 11Footnote 12Footnote 13}. Development of periodontal disease is associated with presence of high numbers of A. actinomycetemcomitans; the estimated bacterial load threshold is 3.3 x 10⁴ A. actinomycetemcomitans cells^{Footnote 14}. Localized aggressive periodontitis is characterized by bone loss around the first molars and incisors, and bleeding at infection sites^{Footnote 15}.

A. actinomycetemcomitans is also involved in many non-oral conditions including endocarditis, endophthalmitis, brain abscess, skin infections, osteomyelitis, septic arthritis, urinary tract infections, pulmonary infections, and spondylitis^{Footnote 16Footnote 17Footnote 18Footnote 19Footnote 20Footnote 21}.

Infective endocarditis caused by A. actinomycetemcomitans can present symptoms including intermittent fever, chills, malaise, and weight loss^{Footnote 22}. Infection has a mean interval from onset of symptoms to diagnosis of 3 months. The overall mortality rate from A. actinomycetemcomitans- associated endocarditis is approximately 18%^{Footnote 14Footnote 17}.

Endophthalmitis caused by A. actinomycetemcomitans can present with mainly decreased visual acuity accompanied by fever and pain. Symptom duration ranges from 3 days to 3 months. Infection is usually effectively resolved using antibiotics and potential vitrectomy. No mortality has been reported^{Footnote 23}.

Osteomyelitis caused by A. actinomycetemcomitans can present symptoms including pain, swelling, pus discharge, and weakness in the affected area. Symptom duration ranges from 2 days to 7 months. Treatment with antibiotics and debridement is usually effective in resolving the infection^{Footnote 24}.

A. actinomycetemcomitans has recently shown significant association with development of coronary disease and atherosclerosis, potentially due to the activation of cross-reactive immune responses^{Footnote 25}.

A. actinomycetemcomitans has been found in non-human primate species and has been detected in domestic felines and canines with periodontal disease^{Footnote 18Footnote 26}.

Epidemiology

A. actinomycetemcomitans infections occur worldwide, present in 10% of normal children and approximately 25-30% of healthy individuals harbour the bacteria^{Footnote 2Footnote 27}.

A. actinomycetemcomitans is commonly associated with severe (chronic) and aggressive periodontitis^{Footnote 13}. Severe periodontitis affects 5-20% of adults globally, while prevalence of aggressive periodontitis is 0.1-5%^{Footnote 13Footnote 28Footnote 29Footnote 30}. Carriage rates of A. actinomycetemcomitans vary geographically and among different ethnic groups, which may be due to host genetics^{Footnote 13}. Presence of the highly leukotoxic JP2 strain is most prevalent in African populations and their descendants, while Asian populations are regularly colonized with A. actinomycetemcomitans serotype c^{Footnote 13Footnote 31Footnote 32}. Serotypes a, b, and c are most prevalent in the oral cavity^{Footnote 1}. The JP2 strain has been observed to infect younger populations under 35 years old, while serotype c infects older populations^{Footnote 33}.

Host range

Natural host(s)

Humans, non-human primates, and domestic felines and canines^{Footnote 26Footnote 27}.

Other host(s)

Rats and guinea pigs are experimentally infected hosts^{Footnote 34Footnote 35}.

Infectious dose

Unknown.

Incubation period

Unknown.

Communicability

Person-to-person transmission can occur via saliva^{Footnote 12Footnote 36}; however the transfer of bacteria does not necessarily result in colonization of the host^{Footnote 37}. Vertical and horizontal transmission of A. actinomycetemcomitans has been reported, although horizontal transmission is more rare than parent-child transmission^{Footnote 38Footnote 39Footnote 40}. Shared toothbrushes, eating utensils, and contact with damaged skin or mucous membranes are possible vehicles of transmission^{Footnote 41Footnote 42Footnote 43}.

Section III - Dissemination

Reservoir

Humans.

Zoonosis

None.

Vectors

None.

Section IV - Stability and viability

Drug susceptibility/resistance

Generally susceptible to carbapenems^{Footnote 6Footnote 44}, mezlocillin^{Footnote 6}, aminoglycosides^{Footnote 6Footnote 45Footnote 46}, fluoroquinolones^{Footnote 6Footnote 44Footnote 46}, cephalosporins^{Footnote 45}, amoxicillin^{Footnote 47Footnote 48}, azithromycin^{Footnote 47}, doxycycline^{Footnote 49}, metronidazole^{Footnote 50}, cotrimoxazole^{Footnote 6}, rifampicin^{Footnote 6}, chloramphenicol^{Footnote 6Footnote 44}, clarithromycin^{Footnote 6}, and azithromycin^{Footnote 6}. Synergistic effects have been observed against A. actinomycetemcomitans when metronidazole and some beta-lactam antibiotics (e.g., amoxicillin, cefixime) are used in combination^{Footnote 51}.

Generally resistant to vancomycin^{Footnote 6}, erythromycin^{Footnote 6Footnote 44}, clindamycin^{Footnote 6}, methicillin^{Footnote 6}, and tetracycline^{Footnote 46}.

Susceptibility to disinfectants

Use of 0.2% chlorhexidine has been demonstrated to have antibacterial effects against A. actinomycetemcomitans isolated from biofilm and cultured on agar^{Footnote 52}. Sodium hypochlorite and hydrogen peroxide are effective against gram-negative biofilm bacteria^{Footnote 53Footnote 54}. Other chemical disinfectants used against closely-related bacteria include chloramine-T^{Footnote 54}, quaternary ammonium compound formulations^{Footnote 54}, 60-90% ethanol and isopropanol^{Footnote 54}, 2.5% glutaraldehyde^{Footnote 55}, 6% formaldehyde^{Footnote 55}, and 6.8% glyoxal^{Footnote 55}.

Physical inactivation

A. actinomycetemcomitans cells can be inactivated by irradiation with blue diode laser (Blue DL) and blue light-emitting diode (Blue LED) or Red DL and Red LED at wavelengths of 450, 430-460, 635, and 630 nm, respectively, and applied energy density of 60J/cm² for 60 seconds^{Footnote 56Footnote 57}. Application of heat at temperatures from 60 to 90^oC for 30 minutes are effective at inactivating strains of A. actinomycetemcomitans^{Footnote 58}.

Survival outside host

A. actinomycetemcomitans have been recovered from blood cultures incubated for more than 14 days^{Footnote 6}.

Section V - First aid/medical

Surveillance

Diagnosis is accomplished through the monitoring of clinical symptoms. A. actinomycetemcomitans can be identified by bacterial isolation on enriched growth media (e.g., chocolate agar) followed by confirmation testing using 16S rRNA sequencing or matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry^{Footnote 59}.

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

Infection can be treated with appropriate antibiotics. Amoxicillin in combination with metronidazole is commonly used to treat A. actinomycetemcomitans infection^{Footnote 50}.

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

No vaccine currently available. However, a novel strategy using outer membrane vesicles as post-exposure vaccination in mice has shown bacterial clearance effects when compared to a control, non-vaccinated group^{Footnote 60}.

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

Prophylaxis

None.

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

None reported to date.

Note: Please consult the Canadian Biosafety Standard and Canadian Biosafety Handbook for additional details on requirements for reporting exposure incidents. A Canadian biosafety guideline describing notification and reporting procedures is also available.

Sources/specimens

Biological samples that may contain A. actinomycetemcomitans include dental plaque, saliva^{Footnote 61Footnote 62}, cardiac tissue^{Footnote 62Footnote 63}, and human blood^{Footnote 6}.

Primary hazards

Exposure of mucous membranes/skin to infectious material and autoinoculation with infectious material are the primary hazards associated with exposure to A. actinomycetemcomitans^{Footnote 18Footnote 63}.

Special hazards

None.

Section VII - Exposure controls/personal protection

Risk group classification

A. actinomycetemcomitans is a Risk Group 2 Human Pathogen and a Risk Group 1 Animal Pathogen^{Footnote 64}.

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 labcoat 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, PM 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

A biological safety cabinet (BSC) or other primary containment devices to be used for activities with open vessels, based on the risks associated with the inherent characteristics of the regulated material, the potential to produce infectious aerosols or aerosolized toxins, the handling of high concentrations of regulated materials, or the handling of large volumes of regulated materials.

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 A. actinomycetemcomitans, 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 before clean up (Canadian Biosafety Handbook).

Disposal

All materials/substances that have come in contact with the regulated materials should 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 A. actinomycetemcomitans require a Human Pathogens and Toxins licence issued by the Public Health Agency of Canada.

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

• Human Pathogen and Toxins Act and Human Pathogens and Toxins Regulations
• Transportation of Dangerous Goods Regulations

Last file update

September, 2023

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, 2023, Canada

References