Yellow Fever Vaccination Under Low Dose Methotrexate Therapy

Brief Summary: Travelers (n = 30, 15 taking low-dose methotrexate (MTX), 15 healthy controls (HC), seeking travel advice in one of the following Swiss Travel Centers (Aarau, Basel, Bern, Geneva, Lausanne, Zurich) and who have an indication for yellow fever (YF) vaccination according to the Swiss Federal Office of Public Health's vaccination recommendations are invited to participate in this study. After signing the consent form (i) YF viremia and (ii) anti-YF antibody production in patients taking low-dose MTX and HC will be compared after YF vaccination. It will be analyzed whether the percentage of people with protective antibodies differs between the two groups and (iii) vaccine side effects will be compared between the groups.

Detailed Description: The study will be conducted in the form of a multi-center open-label prospective observational controlled pilot study. 15 patients under low dose methotrexate treatment and 15 healthy controls with an indication for yellow fever vaccination will be included. The study duration will be 28 days for each subject and will consist of 6 clinical visits on days 0, 3, 7, 10, 14 and 28.

YF antibodies will be measured on days 0, 7, 10, 14 and 28; viremia will be measured on days 3, 7, 10, 14 and 28.

Recruitment & Eligibility

Inclusion Criteria

Exclusion Criteria

Contraindications on ethical grounds
Women who are pregnant or breast feeding
Contraindication against yellow fever vaccination (e.g. hypersensitivity against vaccine ingredient)
Current treatment with other immunosuppressive agent apart from low dose methotrexate
Alemtuzumab or rituximab in the last year
TNF-blocking therapy in past three months
Immunocompromising condition in healthy control
Other immunocompromising condition than MTX treatment itself and the underlying disease in patients under MTX
Previous yellow fever vaccination
No indication for yellow fever vaccination according to Swiss travel vaccination recommendations
Known or suspected non-compliance, drug or alcohol abuse
Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant

Arm && Interventions

Group	Intervention	Description
Patients under low dose methotrexate therapy	Yellow Fever Vaccination	Patients with various underlying conditions (e.g. rheumatic diseases, dermatologic diseases) who have an indication for yellow fever vaccination
Healthy controls	Yellow Fever Vaccination	Healthy travelers who have an indication for yellow fever vaccination

Primary Outcome Measures

Name	Time	Method
Quantitative viremia in blood in travelers under low dose methotrexate (≤20mg/week) and healthy travelers	days 3, 7, 10 and 14 and 28	Serum samples will be collected for PCR
Quantitative yellow fever specific neutralizing antibodies in blood of travelers under low dose methotrexate therapy (≤20mg/week) and healthy travelers	days 0, 7, 10, 14 and 28	Serum samples will be collected for measurement of neutralizing antibodies

Secondary Outcome Measures

Name	Time	Method
Determination of the percentage of travelers with an antibody level of >0.7 LNI (>0.5 IU/ml) in both groups	days 0, 7, 10, 14, 28
Assessment of safety by determining the severity and quantity of adverse vaccine reactions such as local and systemic reactions in both study groups	Throughout day 28 after vaccination	Local and systemic vaccine reactions will be collected in a diray card filled out by the participant

Locations (6): Kantonsspital Aarau
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Aarau, Aargau, Switzerland
Médecine Tropicale et Humanitaire Hôpitaux Universitaires de Genève
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Geneva, Switzerland
PMU | Policlinique médicale universitaire CHUV | Service des maladies infectieuses, Département de médecine
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Lausanne, Switzerland
Universitätsklinik für Infektiologie Inselspital
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Bern, Switzerland
University of Zurich, Epidemiology, Biostatistics and Prevention Institute
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Zurich, Switzerland
Swiss Tropical and Public Health Institute
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Basel, Basel Stadt, Switzerland