CCL3, CCL5, IL-15, IL-1Ra and VEGF compose a reliable algorithm to discriminate classes of adverse events following 17DD-YF primary vaccination according to cause-specific definitions.

In the present study, a range of serum biomarkers were quantified in suspected cases of adverse events following YF immunization (YEL-AEFI) to propose a reliable laboratorial algorithm to discriminate confirmed YEL-AEFI ("A1" class) from cases with other illnesses ("C" class). Our findings demonstrated that increased levels of CXCL8, CCL2, CXCL10, IL-1ß, IL-6 and TNF-α were observed in YEL-AEFI ("A1" and "C" classes) as compared to primary vaccines without YEL-AEFI [PV(day 3-28)] and reference range (RR) controls. Notably, increased levels of CCL3, CCL4, CCL2, CCL5, IL-1ß, IL-15, IL-1Ra and G-CSF were found in "A1" as compared to "C" class. Venn diagrams analysis allowed the pre-selection of biomarkers for further analysis of performance indices. Data demonstrated that CCL3, CCL5, IL-15 and IL-1Ra presented high global accuracy (AUC = 1.00) to discriminate "A1" from "C". Decision tree was proposed with a reliable algorithm to discriminate YEL-AEFI cases according to cause-specific definitions with outstanding overall accuracy (91%). CCL3, CCL5, IL-15 and IL-1Ra appears as root attributes to identify "A1" followed by VEGF as branch nodes to discriminate Wild Type YFV infection ("C(WT-YFV)") from cases with other illnesses ("C*"). Together, these results demonstrated the applicability of serum biomarker measurements as putative parameters towards the establishment of accurate laboratorial tools for complementary differential diagnosis of YEL-AEFI cases.

Late-Relapsing Hepatitis after Yellow Fever.

One patient presented hyporexia, asthenia, adynamia, and jaundice two months after acute yellow fever (YF) onset; plus laboratory tests indicating hepatic cytolysis and a rebound of alanine and aspartate transaminases, and total and direct bilirubin levels. Laboratory tests discarded autoimmune hepatitis, inflammatory or metabolic liver disease, and new infections caused by hepatotropic agents. Anti-YFV IgM, IgG and neutralizing antibodies were detected in different times, but no viremia. A liver biopsy was collected three months after YF onset and tested positive for YFV antigens and wild-type YFV-RNA (364 RNA-copies/gram/liver). Transaminases and bilirubin levels remained elevated for five months, and the arresting of symptoms persisted for six months after the acute YF onset. Several serum chemokines, cytokines, and growth factors were measured. A similar immune response profile was observed in the earlier phases of the disease, followed by more pronounced changes in the later stages, when transaminases levels returned to normal. The results indicated viral persistence in the liver and continual liver cell damage three months after YF onset and reinforced the need for extended follow-ups of YF patients. Further studies to investigate the role of possible viral persistence and the immune response causing relapsing hepatitis following YF are also necessary.

Molecular surveillance of dengue in Minas Gerais provides insights on dengue virus 1 and 4 circulation in Brazil.

Dengue, caused by any of the four types of Dengue virus (DENV) is the most important arbovirus in the world. In this study we performed a molecular surveillance of dengue during the greatest dengue outbreak that took place in Divinópolis, Minas Gerais state, Southeast Brazil, in 2013. Samples from 100 patients with clinical symptoms of dengue were studied and 26 were positive. The capsid/premembrane (CprM) and envelope gene sequences of some samples were amplified and sequenced. Molecular analyses demonstrated that two DENV-1 lineages, belonging to genotype V were introduced and co-circulated in Divinópolis. When compared to each other, those lineages presented high genetic diversity and showed unique amino acids substitutions in the envelope protein, including in domains I, II, and III. DENV-4 strains from Divinópolis clustered within genotype IIb and the most recent common ancestor was probably introduced into the city three years before the 2013 epidemic. Here we demonstrated for the first time the circulation of DENV-4 and the co-circulation of two DENV-1 lineages in Midwest region of Minas Gerais, Brazil. Moreover our analysis indicated the introduction of five DENV-1 lineages, genotype V into Brazil, in different times. J. Med. Virol. 89:966-973, 2017. © 2016 Wiley Periodicals, Inc.