Yellow Fever Vaccine in Patients With Rheumatic Diseases

Study Overview
=================
Brief Summary
-----------------
According to World Health Organization (WHO), since December 2016, Brazil is showing a significant increase in cases of yellow fever in humans. In view of this, vaccination is suitable for residents and travelers to the risk area. However, for immunosuppressed patients there is a formal recommendation not to vaccinate with live virus vaccine. On the other hand, the safety and efficacy of the vaccine has been demonstrated in patients with HIV, and safety and seroconversion have also been demonstrated in patients with rheumatic disease who were inadvertently revaccinated for yellow fever. Faced with the impossibility of leaving the high-risk area for some patients the vaccination could be released to only those who have low level of immunosuppression as suggested by some recommendations of medical societies. The availability of a fractional vaccine in the State of São Paulo, which has proved its efficacy, opens the possibility of exposure to a lower number of copies of the virus in the first exposure of immunosuppressed patients, allowing, if necessary, a safer revaccination, after 28 days to obtain of a more effective immunogenic response. The objectives of the study are to evaluate the immune response of the immunization with fractional yellow fever vaccine (neutralizing antibodies) in patients with systemic autoimmune rheumatic diseases residing in a high-risk area. Secondarily, evaluate the possible association between immunogenicity and vaccination with: demographic data, clinical and laboratory activity of the disease in patients with chronic rheumatic diseases, evaluate the curve of viremia and report adverse events. Patients and healthy controls will be vaccinated for yellow fever in the Immunization Center of Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP). The patients' screening for exclusion and inclusion criteria will be done at the rheumatology outpatient clinic after medical evaluation. For the controls will be the routine screening of the Immunization Center. The vaccination protocol will be a fractional dose of the yellow fever vaccine on day D0 for both groups. Patients will be evaluated on day D0, D5, D10, D30-4 and D365 and controls only on days D0, D10, D30-45 and D365 for aspartate aminotransferase (AST), alanine aminotransferase (ALT), platelets, urea and creatinine, immunoglobulin M (IgM) by immunofluorescence for Yellow Fever, viremia, autoantibodies.

Official Title
-----------------
Evaluation of Yellow Fever Vaccine in Patients With Rheumatic Diseases Under Low Immunosuppression Level and Residing in a Risk Area

Conditions
-----------------
Systemic Lupus, Rheumatoid Arthritis, Spondyloarthritis, Inflammatory Myopathy, Systemic Sclerosis, Mixed Connective Tissue Disease, Takayasu Arteritis, Granulomatosis With Polyangiitis, Sjogren's Syndrome, Juvenile Idiopathic Arthritis, Juvenile Dermatomyositis

Intervention / Treatment
-----------------
* Biological: Yellow Fever vaccine (17D)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Rheumatic disease under low immunosuppression (hydroxychloroquine, sulfasalazine or methotrexate plus prednisone up to 7,5mg/day or leflunomide plus prednisone up to 7,5mg/day), Resident in high risk área for Yellow Fever Exclusion Criteria: Active disease Primary immunodeficiency History of anaphylactic response to vaccine components or egg allergy Living outside the risk area Do not meet criteria for low immunosuppression History of previous immunization with the yellow fever vaccine History of live virus vaccine up to 4 weeks before Individuals who do not agree to participate in the study and/or whose parents do not agree to participate in the study

Ages Eligible for Study
-----------------
Minimum Age: 2 Years
Maximum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Rheumatic diseases patients<br>Vaccination against Yellow Fever, fractional dose (0,1mL) of 17D vaccine | Biological: Yellow Fever vaccine (17D)<br>* Vaccination against Yellow Fever, fractional dose (0,1mL) of 17D vaccine<br>|
| Active Comparator: Healthy controls<br>Vaccination against Yellow Fever, fractional dose (0,1mL) of 17D vaccine | Biological: Yellow Fever vaccine (17D)<br>* Vaccination against Yellow Fever, fractional dose (0,1mL) of 17D vaccine<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with severe adverse events to the fractional dose of Yellow Fever vaccine | Comparison of adverse events rates (based on the Brighton Collaboration diagnostic criteria) between rheumatic disease patients and healthy controls after Yellow Fever vaccine | 10 days | 
| Number of participants with protective levels of antibodies against Yellow Fever vaccine | Comparison of protective antibodies rates (measured by indirect immunofluorescence) against Yellow Fever virus between rheumatic disease patients and healthy controls after Yellow Fever vaccine | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Association of number of patients with protective antibodies levels and disease activity in patients with chronic rheumatic diseases | Association of number of patients with protective antibodies levels against yellow fever and disease activity in patients with chronic rheumatic diseases (measured by systemic lupus erythematosus disease activity index-SLEDAI for systemic lupus erythematosus patients, disease activity score-DAS28 for rheumatoid arthritis patients, manual muscle testing-MMT and disease activity score-DAS for inflammatory myopathies patients, Birmingham Vasculitis Activity Score-BVAS for primary vasculitis patients, juvenile arthritis disease activity score-JADAS for juvenile idiopathic arthritis patients) | 30 days | 
| Number of participants with persistent protective levels of antibodies against Yellow Fever | Comparison of protective antibodies rates (measured by indirect immunofluorescence) against Yellow Fever virus between rheumatic disease patients and healthy controls after Yellow Fever vaccine | 1 year | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
vaccine, Yellow Fever, Rheumatic disease