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Since 2014, Brazil has experienced an unprecedented epidemic caused by chikungunya virus (CHIKV), with several waves of East-Central-South-African (ECSA) lineage transmission reported across the country. In 2018, Rio de Janeiro state, the third most populous state in Brazil, reported 41% of all chikungunya cases in the country. Here we use evolutionary and epidemiological analysis to estimate the timescale of CHIKV-ECSA-American lineage and its epidemiological patterns in Rio de Janeiro. We show that the CHIKV-ECSA outbreak in Rio de Janeiro derived from two distinct clades introduced from the Northeast region in mid-2015 (clade RJ1, n = 63/67 genomes from Rio de Janeiro) and mid-2017 (clade RJ2, n = 4/67). We detected evidence for positive selection in non-structural proteins linked with viral replication in the RJ1 clade (clade-defining: nsP4-A481D) and the RJ2 clade (nsP1-D531G). Finally, we estimate the CHIKV-ECSA's basic reproduction number (R0) to be between 1.2 to 1.6 and show that its instantaneous reproduction number (Rt) displays a strong seasonal pattern with peaks in transmission coinciding with periods of high Aedes aegypti transmission potential. Our results highlight the need for continued genomic and epidemiological surveillance of CHIKV in Brazil, particularly during periods of high ecological suitability, and show that selective pressures underline the emergence and evolution of the large urban CHIKV-ECSA outbreak in Rio de Janeiro., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Moreira et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: To evaluate the accuracy of the current World Health Organization' (WHO) Chikungunya fever (CHIKF) clinical-epidemiological case definition against the gold standard of laboratory diagnosis., Methods: This was a prospective study of patients seeking medical care at an Emergency Department in the metropolitan area of Rio de Janeiro, Brazil, from January to June 2018. Clinical features were recorded. Screening for CHIKF was performed using the RT-qPCR and ELISA-IgM antibody assay. Clinical features of CHIKF RT-qPCR/IgM positive cases were compared with those with other febrile illnesses., Results: 27,900 ED visits were recorded, of which 172 (0.61 %) patients were screened for arboviral illness. The prevalence of laboratory-confirmed CHIKF (Lab-CHIKF) was 110/172 [64 %]. Chikungunya virus RNA was detected in 92/172 (53.5 %) patients, while in 18/80 (10.5 %), only IgM was positive. Compared to CHIKV-negative subjects, patients with CHIKF presented much earlier after the onset of symptoms (2 [1-4] vs. 3.5 [2.5-5], p = 0.007), and more frequently reported arthritis (61.8 % vs. 33.9 %, p < 0.0001), arthralgia (96.4 % vs. 79 %, p < 0.0001), and conjunctivitis (35.5 % vs. 16.1 %, p = 0.007). After adjustments for other clinical predictors, arthritis/arthralgia [aOR: 6 (95 % CI 1.8-19.7)] and the presence of conjunctivitis [aOR: 2.85 (95 % CI 1.30-6.24] were positively associated with lab-CHIKF. The sensitivity, specificity, positive predictive value, and negative predictive value of the WHO CHIKF clinical case definition was 96.3 %, 20.9 %, 68.3 % and 76.4 %, respectively, and accuracy was 0.69 [AUC: 0.69 (95 % CI 0.61-0.75)]., Conclusion: The WHO case definition needs to be improved for better accuracy, especially in areas in epidemics in areas with co-circulation of arboviruses., (Copyright © 2020 Elsevier B.V. All rights reserved.)

HIV-1 infection is characterized by generalized deregulation of the immune system, resulting in increased chronic immune activation. However, some individuals called HIV controllers (HICs) present spontaneous control of viral replication and have a more preserved immune system. Among HICs, discordant results have been observed regarding immune activation and the frequency of different T cell subsets, including Treg and Th17 cells. We evaluated T cell immune activation, differentiation and regulatory profiles in two groups of HICs-elite controllers (ECs) and viremic controllers (VCs)-and compared them to those of cART-treated individuals (cART) and HIV-1-negative (HIV-neg) individuals. ECs demonstrated similar levels of activated CD4+ and CD8+ T cells in comparison to HIV-neg, while cART and VCs showed elevated T cell activation. CD4+ T cell subset analyses showed differences only for transitional memory T cell frequency between the EC and HIV-neg groups. However, VC individuals showed higher frequencies of terminally differentiated, naïve, and stem cell memory T cells and lower frequencies of transitional memory and central memory T cells compared to the HIV-neg group. Among CD8+ T cell subsets, ECs presented higher frequencies of stem cell memory T cells, while VCs presented higher frequencies of terminally differentiated T cells compared to the HIV-neg group. HICs showed lower frequencies of total Treg cells compared to the HIV-neg and cART groups. ECs also presented higher frequencies of activated and a lower frequency of resting Treg cells than the HIV-neg and cART groups. Furthermore, we observed a high frequency of Th17 cells in ECs and high Th17/Treg ratios in both HIC groups. Our data showed that ECs had low levels of activated T cells and a high frequency of activated Treg and Th17 cells, which could restrict chronic immune activation and be indicative of a preserved mucosal response in these individuals., Competing Interests: The authors have declared that no competing interests exist.

Objectives: To investigate the impact of early combined antiretroviral therapy (cART) on inflammation biomarkers and immune activation during acute and early chronic HIV-1 infection., Methods: We included 12 acute (AHI), 11 early chronic (EcHI), and 18 late chronic HIV-1-infected (LcHI) individuals who were treated with cART and 18 HIV-1-uninfected (HIV-neg) individuals. Plasmatic levels of inflammation biomarkers, CD8 + CD38 + HLA-DR + T cell frequencies, CD4 T cell counts, CD4/CD8 ratio, total HIV-1 DNA and plasmatic viral load were evaluated. Mann-Whitney test, Pearson and Spearman correlation, and linear regression models were used for statistical analyses., Results: IP-10, IL-18, and sCD163 were significantly elevated at pre-ART in the AHI and EcHI groups, showing a significant reduction after 6 months of cART in the AHI group, achieving similar levels to the HIV-neg group. For the EcHI group, the IP-10 and sCD163 levels were also significantly reduced on M6-ART; however, IP-10 levels remained higher than in the HIV-neg group, and no significant reduction of IL-18 levels was observed. The CD8 + T cell activation levels were elevated in the AHI and EcHI groups at pre-ART and showed a significant reduction on M6-ART, but they were similar to levels seen for HIV-neg only after 12 months of cART. At pre-ART, IP-10 levels but not IL-18 levels were positively correlated with HIV-1 viral load in the AHI group., Conclusions: Early initiation of cART in HIV infection can reduce systemic inflammation, but the earlier normalization of the inflammation markers was only observed when cART was initiated in the acute phase of infection. A slower dynamic of reduction was observed for CD8 + T cell activation.

Elite controllers (ECs) are rare individuals able to naturally control HIV-1 replication below the detection limit of viral load (VL) commercial assays. It is unclear, however, whether ECs might be considered a natural model of a functional cure because some studies have noted CD4 + T cell depletion and disease progression associated with abnormally high levels of immune activation and/or inflammation in this group. Here, we propose the use of immunological parameters to identify HIV-1 ECs that could represent the best model of a functional cure. We compared plasma levels of six inflammatory biomarkers (IP-10, IL-18, sCD163, sCD14, CRP, and IL-6) and percentages of activated CD8 + T cells (CD38 + HLA-DR + ) between 15 ECs [8 with persistent undetectable viremia (persistent elite controllers) and 7 with occasional viral blips (ebbing elite controllers)], 13 viremic controllers (VCs-plasma VL between 51 and 2,000 RNA copies/mL), and 18 HIV-1 infected patients in combined antiretroviral therapy, with suppressed viremia, and 18 HIV-uninfected controls (HIV-neg). The two groups of ECs presented inflammation and activation profiles similar to HIV-neg individuals, and there was no evidence of CD4 + T cell decline over time. VCs, by contrast, had higher levels of IL-18, IP-10, and CRP and a lower CD4/CD8 ratio than that of HIV-neg ( P  < 0.05). Plasma levels of IL-18 and IP-10 correlated positively with CD8 + T cell activation and negatively with both CD4/CD8 and CD4% in HIV-1 controllers. These results suggest that most ECs, defined using stringent criteria in relation to the cutoff level of viremia (≤50 copies/mL) and a minimum follow-up time of >5 years, show no evidence of persistent inflammation or immune activation. This study further suggests that plasmatic levels of IL-18/IP-10 combined with the frequency of CD8 + CD38 + HLA-DR + T cells can be important biomarkers to identify models of a functional cure among HIV-1 ECs.