National case definition: Cholera

Date of last revision/review: December 2023.

National notification

Only confirmed cases of disease should be notified.

Type of surveillance

Routine case-by-case notification to the federal level.

Case classification

Confirmed case

Laboratory confirmation of infection with or without clinical illness, through isolation of cholera toxin producing Vibrio cholerae serotype O1, O139, or other toxigenic serogroups from an appropriate clinical specimen (e.g., stool, rectal swab, vomit, blood).

Note: Illnesses caused by strains of V. cholerae other than toxigenic V. cholerae should not be reported as cases of cholera. Note that cholera refers to toxigenic V. cholerae while vibriosis refers to both non-toxigenic V. cholerae and other Vibrio spp.

Probable case

Clinical illness in a person who is epidemiologically linked to a confirmed case;

or

Detection of Vibrio cholerae nucleic acid by the ctx or toxR gene with or without clinical illness, in an appropriate clinical specimen (dependent on the test used), using a nucleic acid test (NAT), such as a polymerase chain reaction (PCR).

Note: Culture is required for public health and clinical management. Thus, culture must be performed on NAT-positive (NAT+) specimens to enable molecular typing (e.g., whole genome sequencing) for surveillance, outbreak detection and response, as per Canadian Public Health Laboratory Network (CPHLN) guidance. An isolate may also be required for antimicrobial susceptibility testing (AST) and/or antimicrobial resistance (AMR) predictions to guide clinical treatment and/or for AMR surveillance.

Note: NAT positive specimens should be submitted for culture of V. cholerae and confirmatory testing of the cholera toxin.

Note: NAT-positive (NAT+) and culture-negative (culture–) results would still be considered a probable case.

Laboratory comments

Further strain characterization, including antibiotic susceptibility testing and whole genome sequencing (WGS), is required for epidemiologic, public health, and clinical management.

Although the toxR gene is specific for V. cholerae, it can be present in both toxigenic (ctx+) and non-toxigenic (ctx-) strains. Thus, a proportion of specimens positive for the toxR gene may not cause cholera.

If more than one target is positive on the gastrointestinal NAT panel, it may be indicative of a cross-reaction, co-infection and/or a single organism harbouring these genes. Reflex culture should be performed to confirm all suspect bacterial NAT signals and to meet requirements for epidemiologic, public health, and clinical management of that organism.

Clinical evidence

Clinical illness may be characterized by the following signs or symptoms: Acute and/or profuse watery diarrhea (sometimes described as "rice-water stools"), nausea, leg cramps, myalgias, and/or vomiting. The severity of illness may vary. While not considered clinical illness, asymptomatic infections may also occur.

ICD code(s)

ICD-11 code(s)

ICD-10 code(s)

Type of international reporting

Under Article 6 of the International Health Regulations (IHR) (2005), each State Party shall notify the World Health Organization (WHO) by way of the IHR National Focal PointFootnote 1, and within 24 hours of assessment of public health information, of all events which may constitute a public health emergency of international concern within its territory in accordance with the decision instrument (Annex 2 of the IHRFootnote 2), as well as any health measure implemented in response to those events.

An event involving cholera shall always lead to the utilization of the algorithm in Annex 2 of the IHR, because it has demonstrated the ability to cause serious public health impact and to spread rapidly internationally. The need to notify such events to the WHO will depend upon the outcome of the assessment using the Annex 2 decision instrument.

Note: If the event does not meet the criteria for notification under Article 6 of the IHR, then other IHR-related reporting requirements may still apply with WHO and/or other States Parties, including those under Art. 7 (information-sharing during unexpected or unusual public health events), Art. 8 (consultation with WHO on public health events), Art. 9 (any public health risk that may cause international disease spread), Art. 10 (requests for verification from WHO), and Art. 44 (collaboration and assistance).

Comments

Illnesses caused by strains of V. cholerae other than toxigenic V. cholerae should not be reported as cases of Cholera. Note that cholera refers to toxigenic V. cholerae while vibriosis refers to both non-toxigenic V. cholerae and other Vibrio spp.

Probable case definitions are provided as guidelines to assist with case finding and public health management, and are not for national notification purposes.

Vibrio species (including V. cholerae) are included in several multiplex culture independent diagnostic test (CIDT) panels, so it is possible that more laboratories will routinely test for Vibrio in stool specimens and more laboratory-diagnosed cases will be reported to public health authorities.

Common CIDTs include antigen-based tests and molecular nucleic acid tests (NATs). Although the term CIDT is used by other reporting bodies, Canada has used the terms NAT and PCR in their case definitions to exclude antigen-based CIDTs, which currently are not readily used or available for most enteric bacterial pathogens. In addition, there are concerns regarding the accuracy of antigen-based CIDTs for most bacterial enteric pathogens; thus, the specification of NAT/PCR ensures that an antigen test on the clinical specimen is not interpreted as part of a case count. Note: Some reporting bodies may choose to report NAT and PCR results under the term "CIDT", as they are a form of CIDT when directly performed on the clinical specimen.

NAT-positive specimens for cholera in the probable case definition are specific to the detection of the ctx and/or toxR genes from the NAT. Note: Although the toxR gene is specific for V. cholerae, it can be present in both toxigenic (ctx+) and non-toxigenic (ctx-) strains. Thus, a proportion of specimens positive for the toxR gene may not cause Cholera. In addition, NAT-positive specimens for cholera should be submitted for confirmatory testing of the cholera toxin.

Specific performance characteristics such as sensitivity, specificity, positive predictive value, and negative predictive value of these assays likely depend on the method used. It is therefore useful to collect information on the type(s) of testing performed for reported cases. However, due to the variable performance characteristics of NAT methods and the potential for clinical sample degradation during transit, discordant results may occur between testing methods and laboratories. It is best practise to culture the NAT positive specimen as soon as possible, such as performing culture in the laboratory that generated the NAT positive signal. When a specimen is positive using a NAT, it is strongly advised to collect and document information on all culture results for the specimen (i.e., NAT+/culture+ versus NAT+/culture– versus NAT+/culture not done); this information is helpful to inform the development and implementation of CIDT and associated case definitions at the provincial, territorial and national levels.

Culture is required for public health and clinical management. Thus, culture must be performed on NAT+ specimens to enable molecular typing (e.g., WGS) that are required for surveillance, outbreak detection and response. An isolate may also be required for AST and/or AMR predictions to guide clinical treatment and/or for AMR surveillance.

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