Shigella spp.: Infectious substances pathogen safety data sheet

Section I – Infectious agent

Name
Shigella spp.

Agent type
Bacteria

Taxonomy

Family
Enterobacteriaceae

Genus
Shigella

Synonym or cross-reference
Serogroup A: S. dysenteriae, serogroup B: S. flexneri, serogroup C: S. boydii, serogroup D: S. sonnei, shigellosis, and bacillary dysentery.

Characteristics

Brief description

Shigella spp., of the Enterobacteriaceae family, are gram-negative rod-shaped pathogenic bacteria^{Footnote 1}. They are non-motile, non-encapsulated, non-sporulating, facultative anaerobes that do not ferment lactose, or do so slowly^{Footnote 1Footnote 2}. There are currently four species (subgroups) within the genus Shigella, which are differentiated by their biochemical properties, phage or colicin susceptibility, and whether polyvalent antisera can detect specific polysaccharide antigens^{Footnote 2Footnote 3Footnote 4}. Each species is further subdivided into serotypes based on type specific antigens^{Footnote 2}. S. flexneri and S. sonnei are the most commonly isolated species while S. boydii and S. dysenteriae account for less than 5% of all shigellosis cases globally. The circular genome size varies between species, serotypes, and specific isolates. S. flexneri has a genome of approximately 4.5 Mbp^{Footnote 5}, S. sonnei has a 4.99 Mbp chromosome^{Footnote 6}, the genome of S. boydii has been reported to range from 4.1-4.7 Mbp with a GC content of 50.75%^{Footnote 7}, and S. dysenteriae also has a GC content of 50% with a total genome size of 4.3 Mbp^{Footnote 8}.

Properties

A large virulence plasmid is essential for the pathogenesis of Shigella spp. as it facilitates invasion and spread into macrophages and enterocytes^{Footnote 2}. Several other plasmids and pathogenicity islands (PAIs) have been acquired over the evolution of Shigella spp. that allow for effective invasion of host cells and protection against host immune responses. The plasmid pINV encodes a type III secretion system and several virulence factors, thus, it facilitates the intracellular lifestyle of Shigella spp.^{.Footnote 2}. Shigella spp. also secrete virulence factors that induce inflammation and effectors that down-regulate the host immune response^{Footnote 9}. Several plasmids, such as spA and pKSR100, confer antimicrobial resistance^{Footnote 2}. The largest PAI also gives resistance to antimicrobials, as well as enables iron sequestration and modification of the O antigen through the production of an enterotoxin^{Footnote 2}. The impact of bacteriophages on the evolution and virulence of Shigella spp. is substantial as they are commonly associated with PAIs. Insertion sequence elements are abundant within Shigella spp.^{Footnote 2} leading to genome rearrangements, in addition to gain and/or loss of gene function. There are pathogenic differences between the Shigella spp. S. dysenteriae is considered the most virulent and can produce a potent cytotoxin known as Shigatoxin^{Footnote 10}.

Section II – Hazard identification

Pathogenicity and toxicity

Ingested pathogens can survive gastric acidity and cause illness by infecting the colonic mucosa and multiplying in the colonic epithelial cells and spreading laterally to adjacent cells^{Footnote 11Footnote 12Footnote 13}. Clinical manifestations generally appear between 12 hours to 3 days after exposure^{Footnote 14}. Infection may be mild and asymptomatic, but it is most commonly characterized by acute intestinal infection upon ingestion, resulting in mild watery diarrhea to severe inflammatory bacillary dysentery or shigellosis, manifested by severe abdominal cramps, nausea and vomiting, fever, tenesmus, anorexia, and stool containing blood and mucus^{Footnote 1Footnote 3Footnote 15}. Further complications include Reiter's syndrome which has been associated with S. flexneri^{Footnote 16Footnote 17}, severe dehydration, intestinal perforation, toxic megacolon, bacteremia, toxaemia^{Footnote 18}, septicaemia, seizures, toxic encephalopathy with headache and alterations of consciousness, septic shock and convulsions (very rare)^{Footnote 10}, and haemolytic uremic syndrome, which has been linked to Shigatoxin (a potent cytotoxin produced by S. dysenteriae that can also cause other neurotoxic effects). Symptoms include fever, tachycardia, tachypnea, and hypotension^{Footnote 14}. Infections are usually self-limiting and resolve within 5 to 7 days after symptoms onset, but can become life-threatening in the very young, elderly, or immunocompromised patients or if not properly treated^{Footnote 3Footnote 14}. Severity of infection depends on the host, dose, and serotype^{Footnote 3}. Virulence of Shigella is temperature-regulated, as organisms are able to invade HeLa cells at 37°C and cannot do so in vitro at 30°C^{Footnote 19}. S. dysenteriae is the most pathogenic species, with a fatality rate up to 20%. S. sonnei usually causes mild forms of shigellosis^{Footnote 14}.

Epidemiology

Shigella spp. have a worldwide distribution. S. flexneri is the leading cause of shigellosis in developing countries, causing two-thirds of infections and which mostly affects children^{Footnote 2Footnote 20}. S. sonnei is the most common Shigella species in developed countries. S. boydii and S. dysenteriae cause less than 5% of all cases globally^{Footnote 2}. However, S. dysenteriae serotype 1 is the primary cause of outbreaks in populations experiencing upheaval, resulting in high case fatality due to its production of an exotoxin that is responsible for cytotoxicity and vascular lesions in the colon and other organs^{Footnote 14Footnote 20}. An outbreak of S. dysenteriae in Japan in 1897 had a mortality rate of 25% which resulted in the death of over 22 000 people^{Footnote 21}. In 1969, a multiantibiotic resistant strain of S. dysenteriae caused over 10 000 deaths from dysentery^{Footnote 21}. Since then, there have been four outbreaks caused by S. dysenteriae, thought to be related to population movement and crowding, that occurred in central America (1968-72), south Asia (1980s), central Africa (1980s), and east Africa (1990s)^{Footnote 21}. In 2022, an outbreak of drug resistant S. sonnei has been reported in Tunisia with 96 cases, 6 hospitalizations of children, and 1 fatality in an 8-year-old girl^{Footnote 22Footnote 23}. At the same time, in the Canadian province of Alberta, there was a shigellosis outbreak with S. flexneri among Edmonton's inner-city residents^{Footnote 24}. A total of 115 patients with Shigella infection needed hospitalization over the course of three months, beginning in mid-August 2022. Following a spike of infections in 2022-2023, the Center for Disease Control (CDC) of the United States issued an official health advisory on an extensively drug-resistant shigellosis^{Footnote 25}.

Drug resistant S. sonnei has also emerged in Europe, resulting in a 5-fold increase in cases of gastrointestinal infections among Men who have Sex with Men (MSM)^{Footnote 26}. Due to the dissemination of this bacterium in Europe, the WHO Regional Office for Europe released an alert in March of 2022^{Footnote 26}. Shigellosis outbreaks have been reported in daycare centers and residential institutions in developed areas, as well as in MSM^{Footnote 14}. Outbreaks are also commonly caused by contaminated food or water; however, in developed countries, the likelihood of shigellosis outbreaks due to contaminated water are low^{Footnote 21}. Poor sanitation and hygiene increase the probability of transmission^{Footnote 14Footnote 20}. Globally, the overall incidence of shigellosis is approximately 188 million cases globally per year, resulting in 1 million deaths^{Footnote 14}. Populations that are more likely to develop the disease, or experience more severe disease, include the elderly, very young individuals, and immunocompromised individuals^{Footnote 14}. Increasing age is associated with decreasing prevalence and severity^{Footnote 27}. Persons living in developing countries, international travellers, migrant workers, custodial service workers, children in daycare centers, certain First Nation reserves, MSM, and HIV-infected patients are also considered high-risk groups^{Footnote 12Footnote 14}.

Host range

Natural host(s)

Humans and higher primates^{Footnote 3}.

Other host(s)

Shigella has experimentally infected mice, guinea pigs, domestic pigs, and rabbits^{Footnote 28Footnote 29Footnote 30}. Shigella spp. have also been detected in the fecal samples of goats^{Footnote 31}.

Infectious dose

Infection can result from ingestion of 10 – 200 organisms^{Footnote 14Footnote 32}.

Incubation period

The average incubation period is 1-4 days but can be up to 8 days in the case of S. dysenteriae type 1^{Footnote 20}. Clinical manifestations may present within 12 hours to 3 days^{Footnote 14}. Bacteria begin to be shed in feces 4 weeks after infection, and it is communicable as long as the organisms are present in excrement^{Footnote 12}. Although rare, asymptomatic carriers can also spread the infection for some months^{Footnote 33}.

Communicability

Organisms are spread through the fecal-oral route, and transmission is typically through one of three mechanisms: ingestion of contaminated foods (washed with fecally contaminated water, or handled with poor hygiene, commonly in tossed salads, chicken, and shellfish)^{Footnote 3Footnote 14}; drinking contaminated water (or in swimming pools); or by person-to-person contact by anal sexual contact^{Footnote 12Footnote 14}. Spread of infection linked to flies has also been recorded^{Footnote 12}.

Section III – Dissemination

Reservoir

Humans are the most common reservoir; infections have also been observed in non-human primates^{Footnote 3}. Shigella spp. have also been detected in the fecal samples of goats^{Footnote 31}.

Zoonosis

There are cases of zoonotic transmission of shigellosis between humans and non-human primates^{Footnote 34Footnote 35}. These instances are rare and occur during occupational contact in which an infected non-human primate transmits the bacteria to a human.

Vectors

Flies act as a mechanical vector and disseminate Shigella spp.^{Footnote 3Footnote 20}.

Section IV – Stability and viability

Drug susceptibility/resistance

Susceptible to zinc, ampicillin, trimethoprim, sulfamethoxazole, naldixic acid, ofloxacin, chloramphenicol, fluoroquinolones, cephalosporins, azithromycin, cefixime, ceftibuten, pivmecillinam, ceftriaxone, and ciprofloxacin^{Footnote 12Footnote 14Footnote 20Footnote 36Footnote 37}.

Multidrug-resistant strains are emerging, including those against trimethoprim-sulfamethoxazole (TMP-SMX), ampicillin, and chloramphenicol^{Footnote 36Footnote 38}. Resistance has also been seen for ciprofloxacin, azithromycin, ceftriaxone, and cephalosporins^{Footnote 20}, as well as nalidixic acid, tetracycline, cotrimoxazole, gentamicin, and chloramphenicol^{Footnote 39}. Shigella spp. tend to develop resistance to new antibiotics within 10 years of their release^{Footnote 20}. Antibiotic susceptibility testing is recommended as drug resistance varies regionally and between variants^{Footnote 14}.

Susceptibility to disinfectants

Susceptible to 1% sodium hypochlorite, 70% ethanol, 2% glutaraldehyde, iodines, phenolics, and formaldehyde^{Footnote 40}. The use of antibacterial hand hygiene products containing 0.46% triclosan, 4% chlorhexidine gluconate, or 62% ethyl alcohol, results in a 3 to 4 log reduction in S. flexneri concentration on hands^{Footnote 41}.

Physical inactivation

Organisms can be heat-killed by steam using an autoclave for 1 hour at 100°C under normal atmospheric pressure^{Footnote 42}. S. sonnei was inactivated at 180 J/cm² of 405 nm light inactivated by 5-log₁₀ cfu/mL in liquid suspension and has a 2.10 log₁₀ CFU/plate reduction at 192 J/cm² on agar surface^{Footnote 43}. S. flexneri can be inactivated via exposure to 405 nm light emitting-diode (LED) illumination at 4°C after 120 minutes in PBS (phosphate-buffered saline) and RIF (reconstituted infant formula), and 360 minutes on carrot slices and stainless steel^{Footnote 44}. Acoustic energy density at 1.43 W/mL for 12.75 minutes resulted in a 5-log₁₀ reduction in S. boydii population^{Footnote 45}. Treatments with ozone (1.6 and 2.2 ppm) for 1 minute decreased S. sonnei population in water by 3.7 and 5.6 log₁₀ cfu/mL, respectively^{Footnote 46}.

Survival outside host

Shigella spp. can survive up to months on dry surfaces^{Footnote 47}, up to 10 days in citric juices and carbonated soft drinks, several days on contaminated vegetables^{Footnote 3}, over 3 hours on fingers, 2 – 28 days on metal utensils at 15°C or 0 – 13 days at 37°C, in feces for 12 days at 25°C^{Footnote 48}, and water for under 3 days^{Footnote 49}. Growth is possible at 25°C – 37°C and bacteria can survive at 5°C on MacConkey agar. Flies can carry Shigella for up to 20 – 24 days^{Footnote 50}.

Section V – First aid/medical

Surveillance

Infection from Shigella spp. can be identified by monitoring for symptoms. Serological testing of stool isolates can distinguish and confirm serogroups^{Footnote 12}. Nucleic acid based diagnostic assays are common for the detections of enteric pathogens^{Footnote 20}.

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

Shigella spp. infection can be treated through the administration of appropriate drug therapy. Oral rehydration or electrolyte replacement in dehydrated patients can lead to recovery within days^{Footnote 1Footnote 20}. Antimicrobials may reduce duration of infection, carriage state of the patient, and mortality^{Footnote 3}. Post-exposure administration of antibiotic varies based on demographics and regional resistance^{Footnote 14}. Adults with no risk factors for resistance can be prescribed fluoroquinolone, third-generation cephalosporin is recommended for high-risk patients, and second-generation cephalosporin, ampicillin, and trimethoprim-sulfamethoxazole can be administered if susceptibility is discovered. In infants and young children, azithromycin, cefixime, ceftibuten, and pivmecillinam can be used to treat Shigella spp. infection. Ciprofloxacin and ceftriaxone have also been recommended as first-line treatments^{Footnote 20}. Antibiotic susceptibility testing is highly recommended^{Footnote 14}.

Other treatments aids for severe cases include mechanical ventilation, intravenous fluids, anticonvelsants, and inotropics^{Footnote 10Footnote 20}. Captive infected primates have been treated with antibiotics^{Footnote 34}.

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 vaccines are currently available; however, live and subunit parental vaccine candidates are under review^{Footnote 20Footnote 51}.

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

Prophylaxis

There are no pre-exposure prophylaxis available.

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

Shigella species have been identified to be the most frequently identified agent of laboratory-acquired infections because of their high virulence and low infectious dose^{Footnote 52}. A study from 2001-2004 found 15 cases of laboratory acquired infection^{Footnote 53}. In January 1996 at a university affiliated microbiology lab 6 of 19 medical technologists were infected with S. sonnei as a result of laboratory exposure^{Footnote 54}.

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

Sources/specimens

Organisms can be found in stool samples, rectal swabs, and rarely in blood samples^{Footnote 10Footnote 55}.

Primary hazards

The primary hazard associated with Shigella spp. infection is ingestion, although infection also occurs through person-to-person contact, mechanical vectors, and accidental parenteral inoculation^{Footnote 10Footnote 14}.

Special hazards

Experimentally infected guinea pigs and other rodents have been previously reported to transmit infection to laboratory personnel, although rare^{Footnote 56}.

Section VII – Exposure controls/personal protection

Risk group classification

S. dysenteriae, S. flexneri, S. boydii, and S. sonnei, are Risk Group 2 Human Pathogens and Risk Group 2 Animal Pathogens^{Footnote 57}.

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 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 Shigella spp. 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 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 Shigella spp. require a Pathogen and Toxin licence issued by the Public Health Agency of Canada. Shigella spp. are terrestrial animal pathogens in Canada; therefore, importation of Shigella spp. 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, regulation, or legislation:

• Human Pathogens and Toxins Act and Human Pathogens and Toxins Regulations
• Health of Animals Act and Health of Animals Regulations
• Transportation of Dangerous Goods Act and Transportation of Dangerous Goods Regulations
• National Notifiable Diseases (human)

Last file update

November, 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