Clinical trial NCT03938597: Investigation of Serious Adverse Events Following Vaccination Against Yellow Fever: Emphasis on Genetic Basis and Biological Markers
Official title: Investigation of Serious Adverse Events Following Vaccination Against Yellow Fever: Emphasis on Genetic Basis and Biological Markers
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Drug-Related Side Effects and Adverse Reactions
Keywords: yellow fever vaccine
genetic factors
viscerotropic disease
neurological disease
Lead sponsor: The Immunobiological Technology Institute (Bio-Manguinhos) / Oswaldo Cruz Foundation (Fiocruz)
Sponsor class: OTHER
Collaborators: name: Rockefeller University
First posted: 2019-05-06
Enrollment: 10
Sex: ALL
Minimum age (years): 9
Maximum age (years): 59
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Observational model: OTHER
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: This study will recruit cases of severe adverse event after yellow fever vaccine.

Brief summary: It concerns an investigation aiming to investigate genetic biological(s) marker(s) which allow to identify individuals who have risk of serious adverse events to the yellow fever vaccine. This testing is free of hypothesis, because these markers are still unknown. There is no intervention, and it is not possible to establish primary and secondary outcomes.

Detailed description: The rational for the immunological study by LATIM is the observation made by the group that individuals vaccinated with the 17DD yellow fever vaccine show significant alterations on the levels of expression of genes such as CLEC5A, IFNG, IL6, RNASEL, IRF7, IRF9, STAT2 e OAS1 (8). The study which will be conducted by the Rockefeller University will be focused in the qualitative analysis of the genome and exome of volunteers. The study in LATIM will be focused in the quantitative analysis of mRNA, which, together with the results of sequencing, may help in the search for biomarkers. As the expression of mRNA is restricted to the acute phase of the adverse event, it will be done only during the first 30 days after the beginning of the adverse event.

Eligibility criteria: Inclusion criteria:

* Evidence of a systemic reaction in two or more organs within one month of vaccination with yellow fever vaccine;
* Laboratory evidence of yellow fever vaccine virus (at least one):

Positive culture for more than 7 days after vaccination; RT-PCR ≥ 3 log10 PFU/mL at any day after vaccination; Positive RT-PCR more than 14 days after vaccination; Presence of vaccine virus in tissue by culture, RT-PCR or immunohistochemistry.

* Laboratory exclusion of relevant differential diagnosis such as leptospirosis, viral hepatitis and arboviruses.
* Cases not obeying these strict criteria but that could be plausibly YEL-AVD or YEL-AND may be included, if approved by the investigator or co-investigators.

Exclusion Criteria:

* Cases with adverse event after yellow fever vaccine not severe.

Primary outcomes:
measure: Genetic markers
timeFrame: Time frame: 5 years
Secondary outcomes:
Other outcomes:
Locations:
city: Rio De Janeiro
country: Brazil
facility: Assessoria Clinica / Bio-Manguinhos / Fiocruz
state: RJ
Study officials:
References: