Original Title: Guides et normes: prophylaxie post-exposition à une piqûre de tique par antibiotique pour prévenir la maladie de Lyme, rapport en soutien aux outils de transfert des connaissances, au protocole médical national et au modèle d’ordonnance collective

Authors' objectives: In Québec, asymptomatic individuals bitten by a tick in certain areas of the Eastern Townships, the Montérégie or Outaouais may receive single-dose doxycycline post-exposure prophylaxis (PEP) to prevent Lyme disease. However, several criteria, established by the Institut national de santé publique du Québec (INSPQ), must first be met. Children under 8 years of age and pregnant and nursing women are currently excluded from the PEP eligibility criteria because the use of doxycycline is generally not recommended in these populations. In 2018, to permit better access to this prophylaxis in the Eastern Townships and the Montérégie, collective prescriptions were put in place. However, people who meet the criteria but who seek medical attention outside these regions do not have this facilitated access. It was against this background that the Ministère de la Santé et des Services sociaux (MSSS) asked INESSS to review all the available scientific data on PEP and to develop a Québec’s national medical protocol, together with a collective prescription template. This task is part of the larger project on Lyme disease given to INESSS, which includes developing recommendations and knowledge transfer tools for diagnosing and treating patients with the localized or disseminated stage of this disease.

Authors' results and conclusions: RESULTS: INESSS's systematic reviews concerning antibiotic PEP for the prevention of Lyme disease following a recent tick bite showed that the use of single-dose doxycycline for this indication is based on data considered overall to be of a low level of evidence. Indeed, although the authors of a double-blind randomized controlled trial (RCT) reported single-dose doxycycline to have had a statistically significant effect in preventing the appearance of erythema migrans (EM) at the bite site relative to placebo in subjects aged 12 years and over, limitations that compromise the internal validity of this trial were noted. Furthermore, the generalizability of the results of this trial to the Québec context does not seem guaranteed. As well, given the uncertainties regarding the actual safety and efficacy of single-dose doxycycline PEP and the contradictory recommendations from North American learned societies concerning the use of this prophylaxis, INESSS's work shows that the decision whether to the use single-dose doxycycline to prevent Lyme disease following a tick bite should be made within the context of a shared decision-making process between the clinician and the patient or his/her family, as the case may be. The different management options should be presented (PEP + symptom monitoring vs. symptom monitoring alone), and the benefits and risks of each option should be discussed, together with information on the risk of Lyme disease transmission. In light of the results of the systematic review of the use of doxycycline in children under 8 years of age and the new recommendations from the American Academy of Pediatrics, it is proposed that single-dose doxycycline PEP be made available for this population when the PEP eligibility criteria are met. Indeed, the available data, although they are of a low level of evidence, are reassuring in terms of the risk of dental effects. However, the shared decision-making process seems even more important for this population, since there is no data on the efficacy and safety of single-dose doxycycline for the indication of PEP to prevent Lyme disease in under-8-year-olds. The use of single-dose doxycycline may also be considered in nursing women, since tetracyclines are found in low concentrations in breast milk and since the available data indicate that there is no detectable trace of drug in the serum of exposed infants. Furthermore, according to several specialized databases and reference publications, the short-term use of tetracyclines is compatible with breastfeeding. On the other hand, the available scientific data on the use of doxycycline during pregnancy are considered insufficient to freely recommend PEP in pregnant women who meet the eligibility criteria. Lastly, INESSS's work served to identify the absolute and relative contraindications that need to be taken into consideration before prescribing single-dose doxycycline. As well, this work proposes modifying the recommended dosage in children weighing less than 45 kg. To promote the optimal use of single-dose doxycycline PEP and to approach the experimental conditions in which this intervention was studied, our work has led us to propose two changes to the PEP eligibility criteria: 1) the specimen from the bite site should be documented as being a tick; and 2) the maximum of 72 hours should apply from tick removal, not from the medical visit, to the intended time that doxycycline is to be taken. CONCLUSION: The publication of the Québec’s national medical protocol, the collective prescription template and the knowledge transfer tools developed by INESSS for single-dose doxycycline PEP for the prevention of Lyme disease should help better equip Québec health professionals manage patients who present with a tick bite and establish the indication of PEP, while at the same time involving these patients in making the final decision. Furthermore, the regional public health departments will be able to decide on the relevance of instituting a collective prescription in their region based on the Québec’s national medical protocol and of identifying authorized professionals, which will promote access to PEP when it is indicated and in accordance with a practice harmonized across the province.

Authors' methods: To carry out the task concerning PEP, INESSS conducted systematic reviews of the scientific literature on 1) the efficacy and safety of the antibiotics studied for use as PEP for preventing Lyme disease; 2) the safety of doxycycline in children under 8 years of age and in pregnant and nursing women, regardless of the indication for use; and 3) the best practice recommendations concerning PEP from clinical practice guidelines (CPGs) on Lyme disease. The information obtained from these systematic reviews was enriched with experiential knowledge from clinicians, patients and patient association representatives, and with contextual data specific to Québec. The scientific data and the best clinical practice recommendations were found through a systematic search in several databases and a registry of ongoing clinical studies. Different specialized publications and databases on the use of medications during pregnancy and breast-feeding were consulted. A manual search was performed for (CPGs) or other relevant documents, specifically, by consulting the websites of health technology assessment agencies and those of recognized agencies, organizations, institutions and learned societies in the field of microbiology/infectious diseases or public health. The official product monographs for antibiotics approved by Health Canada or the Food and Drug Administration (FDA) were consulted as well. The bibliographies of the selected publications were examined for other relevant documents. With regard to contextual data, the Google search engine was used to find documents prepared by professional bodies and associations. The respective websites of the MSSS, the INSPQ and the regional public health departments in the Eastern Townships and the Montérégie were consulted. A search was conducted for collective prescriptions published in Québec in 2018. In addition, the stakeholders consulted were invited to share information or documents that would help answer the assessment questions. Lastly, a cross-sectional study was carried out to document the use of single-dose doxycycline for the indication of PEP for preventing Lyme disease in persons covered by Québec's public prescription drug insurance plan (PPDIP) from 2014 to 2018. To gather experiential knowledge, INESSS created an advisory committee consisting of clinicians, including specialists in different disciplines, an expert in parasitology and two patient partners who had been diagnosed with Lyme disease. In addition, an advisory subcommittee was formed to support INESSS in creating both a Québec’s national medical protocol and a collective prescription template for PEP. Consultations with representatives from the Association québécoise de la maladie de Lyme (AQML) and interviews with eight patients who had contracted or still had the disease rounded out the gathering of experiential knowledge.

Project Status: Completed

URL for project: https://www.inesss.qc.ca/publications/repertoire-des-publications/publication/prophylaxie-en-prevention-de-la-maladie-de-lyme.html

Year Published: 2019

URL for published report: https://www.inesss.qc.ca/publications/repertoire-des-publications/publication/prophylaxie-en-prevention-de-la-maladie-de-lyme.html

Requestor: Minister of Health

English language abstract: An English language summary is available

Publication Type: Other

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