Original Title: Avis: Modalités et trajectoire diagnostiques de la coqueluche

Authors' objectives: In Québec, a supraregional-level test performed at the Centre hospitalier universitaire Sainte-Justine is listed in the Répertoire québécois et systèmes de mesure des procédures de biologie médicale (hereafter the Répertoire). This is an "in-house" test (coded 45010) for detecting and differentiating four bacterial targets in patients who might have pertussis: Bordetella pertussis (B. pertussis), Bordetella parapertussis (B. parapertussis), Chlamydophila pneumoniae (C. pneumoniae) and Mycoplasma pneumoniae (M. pneumoniae). This test is available only through the service corridors of one of the four university health and social services networks (RUISs) in Québec’s health-care system, which leads to delays in communicating the results to the requesting physician. To remedy this situation, the institutions in the regions, in particular, the CIUSSS du Saguenay-Lac-Saint-Jean, are calling for a regional option for diagnosing pertussis. This new molecular test would target B. pertussis and B. parapertussis to establish or confirm a diagnosis of pertussis. It was in this context that INESSS assessed the relevance of including or not including in the Répertoire a molecular approach for detecting B. pertussis and B. parapertussis at the regional level, without focusing on any specific commercial kit.

Authors' results and conclusions: RESULTS: DIAGNOSTIC PERFORMANCE The 12 studies selected for the purpose of assessing the performance of NAAT in detecting and differentiating B. pertussis and B. parapertussis varied in terms of their patient inclusion criteria or when the specimens were collected, which was up to 7 to 21 days after symptom onset. In these studies, pertussis was primarily detected in children with clinical symptoms suggestive of the disease at a frequency ranging from 9% to 94%, depending on the study and clinical setting. The number of pertussis cases was generally low in patients with bronchiolitis or who presented only with a persistent cough lasting several days. In adult patients, the frequency of detection of pertussis was below 3%. In addition, an NAAT with two or more targets also detected infections caused by B. parapertussis and co-infections, where B. pertussis could be co-detected with another pathogen of bacterial or viral origin. It should be noted, however, that most of the experts consulted consider the sole detection of B. pertussis and B. parapertussis to be sufficient to establish or confirm a case of pertussis. TURNAROUND TIME In its standards for the surveillance of vaccine-preventable diseases, the WHO recommends, after the receipt of specimens, a two-day turnaround time for the result of a molecular test for establishing or confirming a diagnosis of pertussis. Also, treatment is generally not indicated when the patient has been sick for more than 21 days, hence the need to promptly diagnosis this disease. Furthermore, several studies have emphasized the speed of NAAT in testing for B. pertussis or other pathogens useful in the differential diagnosis of pertussis. According to the clinicians consulted across Québec and certain members of the advisory committee, delays in obtaining molecular test results can either discourage them from ordering a pertussis test or have a negative impact on patient management. ORGANIZATIONAL IMPACT The experts consulted endorsed the introduction of the NAAT to test for B. pertussis and B. parapertussis at the regional level. They feel that access to this test would permit prompt patient management. In addition, the resources previously assigned to transporting specimens to the supraregional laboratory would be available to be reassigned to other purposes. Moreover, the COVID-19 pandemic situation has contributed to the deployment of molecular testing equipment in the regional laboratories across the province. Some of this equipment could be used to perform molecular tests for detecting B. pertussis and B. parapertussis. CONCLUSIONS: The positions of the organizations of interest, the published data on the diagnostic performance of NAAT, the opinions of the experts consulted, and the information regarding the speed of NAAT support the finding that NAAT is the most appropriate laboratory test for establishing or confirming a diagnosis of pertussis. Implementing a molecular test at the regional level would help strengthen the appropriateness of clinical and preventive interventions in the fight against pertussis by permitting rapid isolation, optimizing treatment, and limiting the use of hospitalization. Implementing, at the regional level, a molecular test for confirming a case of pertussis offers several clinical advantages because of quicker access to the test results compared to the turnaround time for the currently available supraregional-level test, but at a higher cost. However, in the absence of an economic model, INESSS cannot rule on the efficiency of regional versus supraregional molecular testing. Given the significant clinical benefits identified in this assessment, INESSS recommends implementing and monitoring the new regional level test for establishing or confirming a diagnosis of pertussis. It also recommends monitoring certain indicators concerning the number of tests performed and their turnaround time, which should be defined in conjunction with the regional public health authorities.

Authors' methods: The strategy for identifying relevant publications was developed in collaboration with INESSS’s scientific information specialists. The initial search was conducted in March 2020, with updates in August 2020 and May 2021. The MEDLINE (PubMed), EMBASE, Evidence-Based Medicine Reviews (EBM), Cochrane, and International Network of Agencies for Health Technology Assessment (INAHTA) databases were queried. The information search was supplemented by consulting the websites of learned societies and professional and regulatory bodies in Canada, the United States, the United Kingdom, Australia, and certain European Union countries. The Google and Google Scholar search engines were used as well. A complementary selection process was used to identify articles on economic analyses of implementing the molecular detection of B. pertussis and B. parapertussis. The methodological quality of the selected publications was assessed using the AGREE II-GRS (Appraisal of Guidelines, for 2 Research, and Evaluation II) instrument. The aspects excluded from this review were primary prevention strategies (vaccination) and all the issues related to the treatment of pertussis. To obtain the perspectives of experts, INESSS created an advisory committee consisting of physicians specializing in medical microbiology, respirology, pediatrics and public health, and experts in laboratory tests and management. In addition, we conducted a consultation in the form of a questionnaire intended for clinicians and other health professionals in Québec who might order a molecular test to establish or confirm a diagnosis of pertussis. The methodology was deployed for five assessment questions: • What are the best practices recommended for establishing a diagnosis of pertussis: the population, signs and symptoms, tests, bacterial targets, and test result turnaround time? • What is, for pertussis, the diagnostic value of a multiplex nucleic acid amplification test (NAAT) with two or more targets? • To what extent does the turnaround time for B. pertussis and B. parapertussis tests for establishing a diagnosis of pertussis affect the patient’s clinical outcome? • What is the organizational impact of implementing, at the regional level, the molecular detection of B. pertussis and B. parapertussis for establishing a diagnosis of pertussis? • What is the budget impact of implementing, at the regional level, the molecular detection of B. pertussis and B. parapertussis for establishing a diagnosis of pertussis?

Project Status: Completed

URL for project: https://www.inesss.qc.ca/en/publications/publications/publication/modalites-et-trajectoire-diagnostiques-de-la-coqueluche.html

Year Published: 2021

URL for published report: https://www.inesss.qc.ca/en/publications/publications/publication/modalites-et-trajectoire-diagnostiques-de-la-coqueluche.html

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: Canada

Province: Quebec

Organisation Name: Institut national d'excellence en sante et en services sociaux

Contact Address: L'Institut national d'excellence en sante et en services sociaux (INESSS) , 2021, avenue Union, bureau 10.083, Montreal, Quebec, Canada, H3A 2S9;Tel: 1+514-873-2563, Fax: 1+514-873-1369

Contact Name: demande@inesss.qc.ca

Contact Email: demande@inesss.qc.ca

Copyright: Gouvernement du Québec