Yellow Fever (YF) vaccination is suggested to induce a large number of adverse events (AE) and suboptimal responses in patients with autoimmune diseases (AID); however, there have been no studies on 17DD-YF primary vaccination performance in patients with AID. This prospective non-interventional study conducted between March and July, 2017 assessed the safety and immunogenicity of planned 17DD-YF primary vaccination in patients with AID. Adult patients with AID (both sexes) were enrolled, along with healthy controls, at a single hospital (Vitória, Brazil). Included patients were referred for planned vaccination by a rheumatologist; in remission, or with low disease activity; and had low level immunosuppression or the attending physician advised interruption of immunosuppression for safety reasons. The occurrence of AE, neutralizing antibody kinetics, seropositivity rates, and 17DD-YF viremia were evaluated at various time points (day 0 (D0), D3, D4, D5, D6, D14, and D28). Individuals evaluated (n = 278), including Valim et al. Yellow Fever Vaccination-Autoimmune Diseases patients with rheumatoid arthritis (RA; 79), spondyloarthritis (SpA; 59), systemic sclerosis (8), systemic lupus erythematosus (SLE; 27), primary Sjögren's syndrome (SS; 54), and healthy controls (HC; 51). Only mild AE were reported. The frequency of local and systemic AE in patients with AID and HC did not differ significantly (8 vs. 10% and 21 vs. 32%; p = 1.00 and 0.18, respectively). Patients with AID presented late seroconversion profiles according to kinetic timelines of the plaque reduction neutralization test (PRNT). PRNT-determined virus titers (copies/mL) [181 (95% confidence interval (CI), 144-228) vs. 440 (95% CI, 291-665), p = 0.004] and seropositivity rate (78 vs. 96%, p = 0.01) were lower in patients with AID after 28 days, particularly those with SpA (73%) and SLE (73%), relative to HC. The YF viremia peak (RNAnemia) was 5-6 days after vaccination in all groups. In conclusion, consistent seroconversion rates were observed in patients with AID and our findings support that planned 17DD-YF primary vaccination is safe and immunogenic in patients with AID.

A osteonecrose é uma terminologia que se refere à morte celular de dois componentes do osso: a medula hematopoiética e os osteócitos. É mais freqüente em homens do que em mulheres (8:1) e a maioria dos casos acontece em pacientes abaixo dos 50 anos de idade. Pacientes infectados pelo vírus HIV encontram-se em maior risco de desenvolver osteonecrose, estando implicados como fatores predisponentes a terapêutica antiviral, ao uso de corticosteróides e outros fatores associados, comuns à população geral. Os autores fazem uma revisão dos aspectos etiológicos, clínicos, patogênicos e diagnóstico, além de aspectos relacionados a esta entidade nos enfermos infectados pelo HIV.

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Background:Alive vaccines should be used with caution in autoimmune diseases (AID).1 Objectives:To evaluate prospectively adverse events and efficacy of the Yellow Fever vaccine in patients with AID.Methods:Prospective study, including 190 individuals, 47 with Rheumatoid Arthritis (RA), 36 primary Sjögren’s Syndrome (SS), 48 Ankylosing Spondylitis (AS), 8 Systemic Sclerosis (SSc), 24 Systemic Lupus Erythematosous (SLE), and 29 Healthy Controls (HC). All individuals received 17DD (Biomanguinhos-FIOCRUZ) YF vaccine, for the first time during the 2017 Brazilian Campaign, aged > 18 years, had no or low disease activity, low immunossupression. Exclusion Criteria: previous vaccination for yellow fever or PRNT > 1:50 at baseline, primary or secondary immunodeficiency, under treatment with cyclophosphamide, chlorambucil, mycophenolate mofetil, calcineurin inhibitors, azathioprine> 2mg/kg/day, prednisone ≥20mg/day, methotrexate >20mg/week or any immunobiological drug. Viremia (CRP) and plaque reduction neutralization test (PRNT; GeoMean title) were measured before (D0) and D3, D4, D5, D6, D7, D14, D28 after vaccine. Adverse events (AE) were registered through patient report diary and medical interview at D7, D14 and D28.Results:Mean age was 52 years old for AID and 56 for HC. No serious adverse event was reported. However, mild local AE was more reported in AID as compared to HC (34.2% vs 3.4%, p=0.000). The frequency of AE was higher in AID compared to HC (34.1 vs. 3.4%). The Risk (Odds Ratio; 95%CI) for AE was 14.53 (1.9-109.7, p=0.000) and AID subgroups: RA=14.5 (1.8-116.2, p=0.0016), AS= 9.3 (1.1-76.2, p=0.0248), SS 25.1 (3.1-204.5, p<0.0001), SLE 9.3 (1.0-84.1, p=0.0377), SSc 56.0 (4.1-769.0, p=0.0014). The PRNT levels expressed in reverse of serum dilution was lower in AID 181 (144-228, p=0.04) as well in AS 112 (73-170, p<0.001), and in SLE 143 (61-332, p=0.01) as compared to HC 440 (291-665). The seropositivity rates were lower in AID after 28 days (78% vs. 96%, p=0.04) as well as in AS (73%, p=0.02) and SLE (73%, p=0.03) as compared to HC (Figure 1). Viremia peak was slightly late and low in AID (D6=5.8 x 103) compared to HC (D5= 8.3 x 103. Seropositivity was statistically lower at D14 in AID as compared HC (21% vs. 75%, p=0.04) and remained lower at D28 in AS and SLE subgroups.Conclusion:Efficacy was lower in AID, especially in SLE and AS, in spite of viremia peak at D5-D6 similar to HC. Taking together, results suggest that YF vaccine is safe in AID with low disease activity and under low immunossupression, but probably a booster dose should be necessary.References[1] Lopez A, Mariette X, Bachelez H, et al. Vaccination recommendations for the adult immunosuppressed patient: A systematic review and comprehensive field synopsis. Journal of Autoimmunity 2017;80:10-27Acknowledgement:SORES and FAPESDisclosure of Interests:None declared

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