Streptococcus pneumoniae: Infectious substances pathogen safety data sheet

For more information on Streptococcus pneumoniae, see the following:

• Infection Control Guideline for the prevention of HCA pneumonia
• Invasive Pneumococcal Disease - Canada.ca

Section I – Infectious agent

Name

Streptococcus pneumoniae

Agent type

Bacteria

Taxonomy

Family

Streptococcaceae

Genus

Streptococcus

Species

pneumoniae

Synonym or cross-reference

Streptococcus pneumoniae^{Footnote 1} is commonly known as the disease it causes, invasive pneumococcal disease (IPD)^{Footnote 2}. It has also be referred to as Micrococcus pneumoniae^{Footnote 3}, or Diplococcus pneumoniae^{Footnote 3} as well as pneumococcus^{Footnote 4Footnote 5}.

Characteristics

Brief description

S. pneumoniae is a gram-positive lancet-shaped bacterium, that is often observed in pairs (diplococci) but can appear as singular or short chains^{Footnote 5}. Most pneumococci are encapsulated with their surfaces being composed of polysaccharides^{Footnote 5}. As pairs, they range from 0.5 to 1.25 µm in length^{Footnote 6}. In addition, pili are also present on the surface of pneumococci^{Footnote 7}. The S. pneumoniae genome is a double-stranded circular genome, and has an average GC content of 39.6% and a median size of 2085 kb^{Footnote 8}.

Properties

S. pneumoniae are non-motile, non-spore forming, facultative anaerobes that are gram positive and catalase negative^{Footnote 5Footnote 6}. Streptococci are classified on the basis of colony morphology, hemolysis, biochemical reactions, and serologic specificity^{Footnote 6}. They are divided into three groups based on the type of hemolysis on blood agar: β-hemolytic (clear, complete lysis of red cells), α-hemolytic (incomplete, green hemolysis), and γ-hemolytic (no hemolysis). S. pneumoniae, is α hemolytic cocci or diplococci^{Footnote 6}.

S. pneumoniae produces a range of virulence factors, including a polysaccharide capsule, surface proteins and enzymes, and a toxin, pneumolysin (PLY)^{Footnote 7}. The capsule of the bacterium is the most important virulence factor. One of its roles in virulence stems from its antiphagocytic activity which is achieved by blocking the deposition of immunoglobulins (Ig) and complement on the pneumococcal cell surface^{Footnote 9}. The capsule is also crucial for colonization, preventing mechanical removal by mucus, as well as restricting autolysis and reducing exposure to antibiotics^{Footnote 7}. PLY is a cholesterol-dependent pore-forming toxin^{Footnote 8}. PLY was shown to be essential for the survival of S. pneumoniae in the respiratory tract, to be involved bacterial dissemination from the lungs to other organs via the bloodstream and to have a pro-inflammatory action^{Footnote 8}. The pili on pneumococci are also virulence factors, as they mediate the binding of the bacterium to cells^{Footnote 7}.

Section II – Hazard identification

Pathogenicity and toxicity

S. pneumoniae is part of the normal flora of the respiratory tract^{Footnote 6}, and it may be isolated from the nasopharynx of up to 90% of healthy persons^{Footnote 5}.

The clinical spectrum of pneumococcal infections ranges from invasive disease (infection of normally sterile sites including osteomyelitis, bacteremia without focus of infection, pneumonia with bacteremia, septic arthritis, and meningitis) to non-invasive infections such as pneumonia without bacteremia, otitis media, and sinusitis^{Footnote 5}. The major clinical syndromes of IPD are pneumonia, bacteremia, and meningitis. In adults, pneumococcal pneumonia is the most common clinical presentation, while bacteremia without a known site of infection is most common for children age 2 years or younger.

For pneumococcal pneumonia, symptoms generally include an abrupt onset of fever and chills or a single rigor^{Footnote 5}. Other common symptoms include pleuritic chest pain, cough productive of mucopurulent, rusty sputum, dyspnea, tachypnea, hypoxia, tachycardia, malaise, weakness, nausea, vomiting, and headaches. Complications of pneumococcal pneumonia include bacteremia, empyema (infection of pleural space), pericarditis, and endobronchial obstruction, with atelectasis (partial collapse of lung tissue) and lung abscess formation. S. pneumoniae is the most common cause of community-acquired pneumonia (CAP) in children and adults^{Footnote 2}.

Bacteremia can occur with or without pneumonia, and can lead to arthritis, meningitis, and endocarditis^{Footnote 5}. While the majority of pneumococcal pneumonia cases are non-bacteremic (60-80%), bacteremic pneumonia is more severe^{Footnote 2}. The case fatality rate for pneumonia with bacteremia is approximately 10%^{Footnote 5}.

The clinical symptoms, cerebrospinal fluid profile, and neurologic complications of pneumococcal meningitis are similar to other forms of purulent bacterial meningitis^{Footnote 5}. Symptoms may include headache, lethargy, vomiting, irritability, fever, nuchal rigidity, cranial nerve signs, seizures, and coma. The case fatality rate of pneumococcal meningitis is approximately 14% among adults, with neurologic sequelae common among survivors^{Footnote 5}.

Bacteremia without a known site of infection and bacteremic pneumonia account for 40% and 25-30% of IPD in children, respectively^{Footnote 5}. S. pneumoniae has become the leading cause of bacterial meningitis among those younger than age 5 years in the United States.

S. pneumoniae is the most common pathogen causing acute otitis media, and it is estimated that 80-90% of children have at least one acute otitis infection before the age of three^{Footnote 10}. The infection is characterized by inflammation and accumulation of purulent fluid, fever, and discomfort/pain.

Uncommon clinical manifestations of S. pneumoniae include gastrointestinal, cardiovascular, genitourinary, bone, pulmonary, ophthalmologic, skin and soft tissue infections^{Footnote 11}.

There are currently 100 recognized serotypes^{Footnote 12}, each being associated with specific clinical manifestations and mortality rates^{Footnote 13}.

Epidemiology

Pneumococcal disease occurs throughout the world (not geographically restricted)^{Footnote 5}, however, serotype distribution varies geographically^{Footnote 2Footnote 14}.

S. pneumoniae is endemic globally; however, in 2015, morbidity rates in children were highest in Southeast Asia (2509 per 100,000), followed by Africa (1603 per 100,000) and Eastern Mediterranean (1261 per 100,000)^{Footnote 15}. In 2016, global incidence in all ages was 26.7 per 1000 people, but the incidence was 70.7 per 1000 for children under 5 years of age and 72.8 per 1000 for elderly adults over 70 years of age^{Footnote 15}. In Canada, the annual incidence rate for all ages between 2009-2019 has remained at a range of 9.0-10.9 cases per 100,000^{Footnote 16}. The incidence for patients under 5 years of age has decreased from 20.8 to 11.5 cases per 100,000, while the incidence for patients over 60 years of age has remained stable at around 19.9 to 23.4 cases per 100,000^{Footnote 16}. In Europe and the United States, the annual incidence of IPD ranges from 10 to 100 cases per 100,000 people^{Footnote 13}. Pneumococcal meningitis in adults accounts for 50% of all bacterial meningitis cases in the US, at 3000-6000 cases per year^{Footnote 13}. It is estimated that pneumococcal meningitis causes 60,000 deaths and long-term sequelae worldwide annually in children <5 years of age^{Footnote 2}.

In a systematic review on S. pneumoniae outbreaks published from 1977-2017, 94 unique outbreaks were reported^{Footnote 17}. The median attack rate was 7.0%, and the median case-fatality rate was 12.9%. 60.3% of outbreaks were reported in older adults and the majority of reported outbreaks were in crowded indoor places, such as hospitals, community spaces, and military spaces^{Footnote 17}.

Pneumococcal infections are most common during the winter and early spring months^{Footnote 5Footnote 6Footnote 18}. While S. pneumoniae infections can occur in all populations, it is more common in patients older than 65 years and younger than 2 years of age^{Footnote 6Footnote 18}. For both children and adults, having certain medical conditions like immunosuppressive conditions^{Footnote 5Footnote 13}, functional or anatomic asplenia, chronic heart disease, renal disease, diabetes^{Footnote 13}, lung disease (including asthma)^{Footnote 5}, liver disease, and having a cerebrospinal fluid (CSF) leak, may cause a higher risk of IPD. In particular, immunosuppressed conditions that lead to higher risk include HIV infection^{Footnote 13}, solid organ or hematopoietic cells transplantations, and sickle cell disease^{Footnote 5Footnote 13}. Other factors of higher risk for IPD include smoking cigarettes, alcoholism, and having a cochlear implant^{Footnote 5Footnote 13}. Rates of IPD are also increased among children of certain racial and ethnic groups, including Alaska Natives, African Americans, and certain Indigenous groups^{Footnote 5}. During seasonal and pandemic influenza, S. pneumoniae secondary bacterial infection is a key contributor to death^{Footnote 19}.

Host range

Natural host(s)

The natural host for S. pneumoniae is humans^{Footnote 6}. S. pneumoniae has also been found in wild chimpanzees^{Footnote 20}.

Other host(s)

In experimental and captivity settings, other hosts include chimpanzees^{Footnote 20}, rodents (mice and rats)^{Footnote 21Footnote 22}, dogs, horses, cats^{Footnote 22}, dolphins, guinea pigs, gorillas, and baboons^{Footnote 22Footnote 23}.

Infectious dose

The infectious dose for S. pneumoniae is unknown. However, in experimental settings, through injection and inhalation, concentrations of 10⁶-10⁹ colony forming units (CFU) have been shown to cause varying amounts of disease in baboons, rats, and mice^{Footnote 23Footnote 24Footnote 25Footnote 26}.

Incubation period

The incubation period for pneumococcal pneumonia has been reported to be as short as 1-3 days^{Footnote 5}.

Communicability

The most common mode of transmission for S. pneumoniae is via respiratory secretions and droplets being inhaled or coming into contact with mucous membranes^{Footnote 4Footnote 5}. Transmission involves either direct person-to-person contact or indirect contact through contaminated surfaces^{Footnote 4}. The direct contact can be either casual or intimate. Autoinoculation is also a possible mode of transmission in experimental settings^{Footnote 23Footnote 24Footnote 26Footnote 27}.

Section III – Dissemination

Reservoir

S. pneumoniae is a common agent that colonizes asymptomatically within the human respiratory tract^{Footnote 5Footnote 6Footnote 12}.

Zoonosis

Although there has not been any cases of S. pneumoniae infection arising from exposure to affected animals, cases of reverse zoonosis in which animal infections with pathogens originating from humans have been reported in wild and domestic animals^{Footnote 20Footnote 21}.

Vectors

None.

Section IV – Stability and viability

Drug susceptibility/resistance

S. pneumoniae is susceptible to beta-lactams^{Footnote 28}, macrolides, fluoroquinolones (specifically moxifloxacin and levofloxacin), doxycycline, clindamycin^{Footnote 29}, telithromycin, linezolid, and vancomycin. Specific beta-lactams used include penicillins such as amoxycillin, penicillin G, and penicillin V^{Footnote 28}; cephalosporins such as cefotaxime, ceftriaxone, cefpodoxime, and cefuroxime; and carbapenems^{Footnote 29}. In addition, the macrolides that could be used include azithromycin, clarithromycin, and erythromycin^{Footnote 28}.

Resistance to antibiotics has been becoming increasingly common^{Footnote 5}. Resistance has been reported for beta-lactams such as penicillin^{Footnote 2Footnote 5Footnote 30}, cephalosporins including cefuroxime^{Footnote 2}, and fluoroquinolones including levofloxacin^{Footnote 28Footnote 30}; macrolides such as erythromycin^{Footnote 2Footnote 28Footnote 30}; tetracycline^{Footnote 2}; clindamycin; trimethoprim-sulfamethoxazole (TMP-SMX) which is also known as cotrimoxazole^{Footnote 28}; and chloramphenicol. The prevalence rate of penicillin resistance is between 13.8-41.8%^{Footnote 31}. Out of all the available antibiotics, resistance to fluoroquinolones remains low with reported resistance rates being 1.0% in the US, 0-1.4% in Canada, 2.6% in China, and 0.5-5.6% in Spain^{Footnote 29}.

Susceptibility to disinfectants

S. pneumoniae is susceptible to 70% isopropyl alcohol (scrub for 30 seconds)^{Footnote 32}, 0.55% ortho-phthalaldehyde solution (immersion for 5 minutes), 70% ethanol^{Footnote 33}, 1% sodium hypochlorite, formaldehyde, hydrogen peroxide, phenolic disinfectants, 0.5% glutaraldehyde^{Footnote 34}, and povidone iodine (PVP-1)^{Footnote 35}.

Physical inactivation

S. pneumoniae can be inactivated by moist heat (121°C for at least 15 minutes), dry heat (160-170°C for at least 1 hour), and heat suspension in a water bath at 56°C for 30 minutes^{Footnote 33}.

Survival outside host

S. pneumoniae has been reported to be able to survive for 7 days in sputum, 1-11 days on glass, and 2-15 on gauze^{Footnote 33}.

Section V – First aid/medical

Surveillance

The most prevalent method to identifying S. pneumoniae by isolating it^{Footnote 5Footnote 6}. Reported characterization can be based on bile solubility^{Footnote 6Footnote 22}, optochin susceptibility^{Footnote 6Footnote 20Footnote 22}, Gram staining^{Footnote 6Footnote 22}, the quellung (capsular swelling) reaction (also known as the Neufeld test)^{Footnote 6Footnote 12}, morphology^{Footnote 20}, and α-hemolysis. Antigen tests based on an immunochromatographic membrane technique to detect the C-polysaccharide antigen of the bacteria is commercially available (and approved by the Food and Drug Administration [FDA])^{Footnote 5}. Additionally, other tests can be used to identify S. pneumoniae along with determining serotypes include polymerase chain reaction (PCR)^{Footnote 12Footnote 20}, multi locus sequence typing (MLST), real time PCR (rt-PCR), and pulsed-field gel electrophoresis (PFGE)^{Footnote 12}.

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

Treatment of infections typically relies on antibiotics^{Footnote 12Footnote 28}. Penicillin has been the standard drug for over 50 years. Due to antibiotic resistance strains and antibiotic allergies, antibiotics aren't always effective therapies^{Footnote 28}. For penicillin resistant strains, third-generation cephalosporins, such as cefotaxime or ceftriaxone are recommended^{Footnote 28}. Macrolides, doxycycline, or fluoroquinolones can be use for previously healthy patients and beta-lactams in combination with macrolides for patients with comorbidities or resistant strains. Fluoroquinolones have been used for patients with an allergy to penicillin or beta-lactams with a combination with other antibiotics in hospitalized cases^{Footnote 29}.

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

Two types of vaccines have been approved for use against S. pneumoniae, pneumococcal polysaccharide vaccines (PPSVs) or pneumococcal conjugate vaccines (PCVs)^{Footnote 5Footnote 13Footnote 36}. In Canada conjugate vaccines approved for use include Pneu-C-10, Pneu-C-13, Pneu-C-15, Pneu-C-20 and Pneu-C-21 while Pneu-P-23 is the only approved polysaccharide vaccine^{Footnote 37}.

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

Prophylaxis

Pre-exposure prophylaxis relies on the administration of one of the two available kinds of vaccines^{Footnote 13Footnote 36}. Post-exposure prophylaxis includes the usage of antibiotics^{Footnote 28Footnote 29}.

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

78 laboratory-acquired cases were reported prior to 2000^{Footnote 33}.

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

Sources/specimens

S. pneumoniae can be isolated from cerebrospinal fluid (CSF)^{Footnote 5Footnote 6Footnote 35Footnote 38}, blood, sputum^{Footnote 6}, middle ear fluid/aspriates^{Footnote 5}, joint fluid, urine, peritoneal fluid^{Footnote 5Footnote 36Footnote 38}, pleural, synovial fluid, and abscess aspirates^{Footnote 38}.

Primary hazards

Inhalation of airborne or aerosolized infectious material as well as exposure to mucous membranes are the primary hazards associated with S. pneumoniae exposure^{Footnote 4Footnote 5}.

Special hazards

Work with experimentally or naturally infected organisms with S. pneumoniae infection can present a special hazard^{Footnote 20Footnote 21}.

Section VII – Exposure controls/personal protection

Risk group classification

Streptococcus pneumoniae is a Risk Group 2 human pathogen and a Risk Group 2 animal pathogen^{Footnote 3}.

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, 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 transmission via inhalation of aerosols containing bacterial cells of Streptococcus pneumoniae justifies the use of a biological safety cabinet (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 are 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 Streptococcus 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 with 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 Streptococcus pneumoniae require a Pathogen and Toxin licence issued by the Public Health Agency of Canada. S. pneumoniae is a terrestrial animal pathogen in Canada; therefore, importation of S. pneumoniae requires an import permit under the authority of the Health of Animals Regulations (HAR). The PHAC issues a Pathogen and Toxin Licence which includes a Human Pathogen and Toxin Licence and an HAR importation permit.

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

• Human Pathogens and Toxins Act and Human Pathogens and Toxins Regulations
• Health of Animals Act and Health of Animals Regulations
• National notifiable disease (human)

Last file update

August, 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