Mycoplasma pneumoniae: Infectious substances pathogen safety data sheet

For more information on Mycoplasma pneumoniae, see the following: Infection prevention and control guideline- Prevention of Healthcare-Associated Pneumonia

Section I – Infectious agent

Name

Mycoplasma pneumoniae

Agent type

Bacteria

Taxonomy

Family

Mycoplasmoidaceae

Genus

Mycoplasmoides

Species

Mycoplasmoides pneumoniae

Synonym or cross-reference

Eaton agent, walking pneumonia, primary atypical pneumonia, pleural atypical pneumonia^{Footnote 1Footnote 2}.

Characteristics

Brief description

Mycoplasmoides pneumoniae is a Gram-negative spindle shaped pleomorphic bacterium, measuring 1-2 μm long by 0.1-0.2 μm wide^{Footnote 1}. M. pneumoniae is motile, using gliding motility instead of pili or flagella. M. pneumoniae lacks a cell wall and has a three-layered membrane containing sterols which provide structural support. The cell membrane is also supported by a protein network which creates a cytoskeleton. M. pneumoniae colonies are up to 100 μm in diameter, primarily colonizing the respiratory tract, and a stereomicroscope is necessary to be able to observe them^{Footnote 2}. The circular genome of M. pneumoniae is 816 kbp long, consisting of 730 genes with an average GC content of 40%^{Footnote 3}.

Properties

M. pneumoniae is considered an atypical pathogen which metabolizes glucose^{Footnote 1}. It is the smallest self-replicating organism capable of cell-free existence^{Footnote 2}. The M. pneumoniae genome encodes for proteins that increase the virulence of the bacterium, such as adhesins that help attach to host respiratory epithelial cells, metabolites, and toxins that are released to induce cytotoxicity, oxidative damage, apoptosis, immune-pathological damage to host cells, and immune evasion abilities^{Footnote 4Footnote 5}. M. pneumoniae may persist in the respiratory tract for variable time periods even after clinical manifestations no longer appear^{Footnote 5}.

M. pneumoniae particularly adheres to respiratory epithelial cells^{Footnote 1Footnote 5}. Adherence to host cell surface receptors allows M. pneumoniae to obtain nutrition but induces metabolism and structural changes in the host cell^{Footnote 6}. After adherence, toxins, peroxide, and superoxide are released into host cells to produce cytotoxicity and directly damage the host cell. These components induce the activation of host inflammatory pathways through the upregulated release of pro-inflammatory cytokines which then produces inflammation damage. As M. pneumoniae invades host cells, mechanisms to evade host immune cells are activated. Mechanisms to evade host immunity include releasing nucleases and enzymes to degrade neutrophil extracellular traps and peroxides released by the host cell, intracellular invasion, DNA recombination allowing for greater antigenic variation, and releasing metabolites which damage lymphocytes. The severity of disease is related to the degree of response from the host immune system^{Footnote 7}.

Section II – Hazard identification

Pathogenicity and toxicity

The majority of M. pneumoniae infections in adults are asymptomatic, but M. pneumoniae is the cause of many upper respiratory tract infections (up to 50% of cases)^{Footnote 2}. Symptoms develop over several days and persist for weeks to months, with common symptoms including sore throat, hoarseness, fever, cough (may be purulent), headaches, coryza, earache, myalgias, chills, and general malaise^{Footnote 2Footnote 5}. There may also be dyspnea in the more severe cases and, in some cases, the cough may take on a pertussis-like character^{Footnote 2}.

Some children may develop inflammation of the throat, cervical adenopathy, conjunctivitis, and myringitis^{Footnote 2}. Progression to pneumonia is rare for children under five years of age, but common for those between 5 and 15 years old^{Footnote 2}. M. pneumoniae is responsible for up to 40% cases of community-acquired pneumonia in children over 5, including primary atypical pneumonia and tracheobronchitis^{Footnote 1}. Infections can be severe in the elderly or immunocompromised^{Footnote 2}.

Complications may occur before, during, or after respiratory symptoms, and may also occur without respiratory syndrome^{Footnote 2}. The most common complications involve the central nervous system, which up to 10% is severe enough to require hospitalization^{Footnote 8}. The most common neurological complication in children is encephalitis^{Footnote 9}. Other reported complications include aseptic meningitis, cerebellitis, meningoencephalitis, acute disseminated encephalomyelitis, polyneuropathy, stroke/cerebral infarction, coma, optic neuritis, diplopia, mental confusion, acute psychosis, polyradiculitis, and cranial nerve palsy^{Footnote 2Footnote 8Footnote 10Footnote 11Footnote 12Footnote 13Footnote 14}.

Complications affecting the motor system include brachial plexus neuropathy, ataxia, chorioathetosis, and ascending paralysis (Guillain-Barré syndrome)^{Footnote 9}. Musculoskeletal complications such as nonspecific myalgias, arthralgias, and polyarthropathies occur in about 14% of patients^{Footnote 2}. Up to 25% of infections may lead to dermatological manifestations, including Stevens-Johnson syndrome, erythematous macropapular and vesicular rashes, mucositis, erythema multiforme, and toxic epidermal necrolysis^{Footnote 2Footnote 4}. Other reported complications include necrotizing pneumonitis, bladder incontinence, pericarditis, arthritis, atherosclerosis, nephritis, pancreatitis, and anemia^{Footnote 2Footnote 13Footnote 15Footnote 16Footnote 17Footnote 18}.

Epidemiology

M. pneumoniae occurs worldwide, but there are more cases in temperate climates^{Footnote 2Footnote 19}. There is a slight gender difference in certain age groups^{Footnote 2}. The most common age for symptomatic infection is 5-15 years of age, while outbreaks among elderly individuals and infants occur only occasionally^{Footnote 19}. Outbreaks tend to occur in late summer and early fall, and there are cyclic epidemics every 3-6 years in civilian and military populations^{Footnote 1Footnote 2Footnote 19}. Infection rates vary between 1.3% to 50% during epidemic periods^{Footnote 20}. Outbreaks commonly occur in closed or semi-closed communities such as hospitals, schools, military bases, and religious communities^{Footnote 1Footnote 2}. Infection is more severe in immunocompromised individuals and those with co-morbid conditions such as functional asplenia, sickle cell disease, and hypogammaglobulinemia^{Footnote 2Footnote 5Footnote 7}.

Host range

Natural host(s)

Humans are the only known natural host for M. pneumoniae^{Footnote 2}.

Other host(s)

Mice^{Footnote 21}, guinea pigs^{Footnote 22}, hamsters^{Footnote 23}, baboons^{Footnote 24}, and chimpanzees^{Footnote 25}.

Infectious dose

Less than 100 CFU^{Footnote 19}.

Incubation period

4 to over 23 days^{Footnote 2}.

Communicability

M. pneumoniae is principally transmitted by aerosol inhalation of droplets or contact of droplets with mucous membrane tissues of the respiratory tract, and may be transmitted by fomites to those in close contact with an infected person^{Footnote 2}. As a result, secondary cases among close contacts are frequent, but since the shedding period is long (ranging from 2 to 8 days before onset of symptoms and as long as 14 weeks after infection), contamination may take weeks^{Footnote 2Footnote 19}. A case of transplacental transmission of M. pneumoniae has been reported^{Footnote 26}.

Section III – Dissemination

Reservoir

Humans^{Footnote 2}.

Zoonosis

None.

Vectors

None.

Section IV – Stability and viability

Drug susceptibility/resistance

M. pneumoniae is susceptible to most common antibiotics such as macrolides (specifically erythromycin, clarithromycin, azithromycin, clindamycin, and moderately pristinamycin, josamycin, spiramycin, and midecamycin), ketolides (specifically telithromycin, cethromycin, and CEM-101), tetracyclines (including doxycycline), and fluoroquinolones (specifically gemifloxacin)^{Footnote 27}. M. pneumoniae shows weaker susceptibility to lincomycin, pefloxacin, chloramphenicol, and gentamicin. M. pneumoniae is resistant to nalidixic acid, cephalosporins, penicillins, rifampicin, sulfonamides, and trimethoprim^{Footnote 27Footnote 28}. M. pneumoniae lacks a cell wall and is therefore resistant to cell wall synthesis inhibitors (e.g. b-lactams, glycopeptides, and fosfomycin)^{Footnote 27}. Some strains of M. pneumoniae are becoming increasingly resistant to macrolides^{Footnote 27Footnote 29}.

Susceptibility to disinfectants

70% ethanol after 5 minutes of exposure, alkaline detergents at 0.8%, and vaporized hydrogen peroxide (180-1200 ppm) are effective against M. pneumoniae^{Footnote 30}. Other Mycoplasma are inactivated by Triton X-100 and sodium deoxycholate (0.25% or higher for 30-60 minutes), cetyltrimethylammonium bromide (0.08% or higher for less than 30 minutes), formaldehyde (0.1-0.2%), and incubation with 0.1% beta-propiolactone (for 1-24 hours)^{Footnote 31}.

Physical inactivation

M. pneumoniae is inactivated by heating at 60 ^oC for 30 minutes^{Footnote 32}, gamma radiation at 25-40 kGy^{Footnote 33}, and UV-radiation at 220 µmw/cm² for 7.5 seconds^{Footnote 34}.

Survival outside host

If protected from evaporation, M. pneumoniae can survive for one hour in liquid, at least 4 hours in air, and 4 hours on stainless steel at room temperature^{Footnote 30Footnote 35Footnote 36}. Airborne survival time is generally higher when relative humidity (RH) is lower. 50% of the sample survives for 4 hours at 10% RH, 35% at 25% RH, 20% at 90 % RH and less than 10% at 60% and 80% RH^{Footnote 36}.

Section V – First aid/medical

Surveillance

Monitor for symptoms. Diagnosis can be done through the complement fixation test which measures early IgM response, however this test has low sensitivity and specificity^{Footnote 1}. Serologic tests can also be used, however, results can only be available weeks after the illness, and results vary according to reinfection and immunosuppressive conditions. Culture with immunofluorescent antibody (IFA) test, other particle agglutination antibody assays, and enzyme immunoassays (EIA) can also be used, with higher sensitivity. PCR has been used with the advantages of quick turnaround time and high sensitivity. The current recommendation is a combination of PCR and serologic tests.

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 (CBH).

First aid/treatment

Macrolides are the first-line treatment for M. pneumoniae infection, specifically erythromycin (25-50 mg/kg/day for 14 days), clarithromycin (10-15 mg/kg/day for 10 days), and azithromycin (10 mg/kg/day for 3 days)^{Footnote 37}. For suspected macrolide-resistant infections, tetracyclines are recommended, such as doxycycline (4 mg/kg/day for 7-14 days)^{Footnote 37Footnote 38}. However, tetracyclines are contraindicated in young children. Fluoroquinolones are another alternative, but are contraindicated in children as well.

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 CBH.

Immunization

No vaccine is currently available in Canada; however, various vaccines have been developed without much effectiveness for protecting against infection^{Footnote 4Footnote 39}.

Note: More information on the medical surveillance program can be found in the CBH, 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 CBH.

Section VI – Laboratory hazard

Laboratory-acquired infections

None reported so far.

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

Sources/specimens

M. pneumoniae may be found in any type of clinical specimen, but more commonly in respiratory tract specimens^{Footnote 2}.

Primary hazards

Exposure of mucous membranes to infectious material and inhalation of airborne infectious material are primary hazards associated with exposure to M. pneumoniae^{Footnote 2}.

Special hazards

None.

Section VII – Exposure controls/personal protection

Risk group classification

Mycoplasmoides pneumoniae is a Risk Group 2 Human Pathogen and Risk Group 1 Animal Pathogen^{Footnote 40Footnote 41}.

Containment requirements

Containment Level 2 facilities, equipment, and operational practices outlined in the CBS 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 CBS 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

The high likelihood of infection or disease arising from airborne transmission of M. pneumoniae 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 M. pneumoniae, 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 (CBH).

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 (CBH).

Storage

The applicable Containment Level 2 requirements for storage outlined in the CBS 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 M. pneumoniae 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
• Transportation of Dangerous Goods Act and Transportation of Dangerous Goods Regulations

Last file update

December, 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, 2024, Canada

References