Synergism between chikungunya virus infection and rheumatoid arthritis on cytokine levels: Clinical implications?

Post-chikungunya virus (CHIKV) chronic arthritis shares several immunopathogenic mechanisms with rheumatoid arthritis (RA), which has led to discussions about the probable relationship between the two diseases. Indeed, some studies have suggested a role for CHIKV infection in RA development. However, to the best of our knowledge, the influence of CHIKV on previous RA has not yet been demonstrated. Herein, we analyzed the potential synergism between CHIKV infection and RA on cytokine and chemokine levels. For this, we compared the IL-1ß, IL-6, IL-10, IL-17A, CCL2, CXCL8, CXCL9 and CXCL10 levels, in addition to rheumatoid factor (RF) and C-reactive protein (CRP), in patients with post-CHIKV chronic arthritis (named CHIKV group), patients with RA (RA group), and patients with previous RA who were later infected by CHIKV (RA-CHIKV). History of CHIKV infection was confirmed by serology (IgG, ELISA). Cytokines/chemokines were quantified by flow cytometry. RF, CRP, age and sex data were obtained from medical records. IL-1ß, IL-6, IL-10 and IL-17A levels were significantly higher in RA-CHIKV compared to the other groups. CXCL8 levels were higher in the CHIKV group than in RA. CXCL9 was higher in CHIKV than in the RA-CHIKV group. CXCL10 was higher in CHIKV than in the other groups. FR levels were higher in RA than in the CHIKV group, and in RA-CHIKV than in CHIKV. No significant difference was observed in CCL2 and CRP, as well as in age and sex. Finally, our findings suggest an interplay between CHIKV infection and RA, which must be analyzed for its possible clinical impact.

Analysis of seroprevalence and risk factors for hepatitis E virus (HEV) in donation candidates and blood donors in Northeast Brazil.

Oral transmission is the main route of hepatitis E virus (HEV) infection; however, genotypes 3 and 4 may also be transmitted by blood transfusion. Individuals who need blood products are often immunosuppressed, which increase the risk of severe disease and death by HEV. Despite this, blood banks in Brazil do not screen for HEV and epidemiological studies in this population are rare; this is an important issue as HEV-3 is frequently identified in the country. Herein, we analyzed the seroprevalence and risk factors for HEV seropositivity in donor candidates/blood donors from Northeast Brazil. Nine hundred and ninety-six donor candidates/blood donors from Foundation of Hematology and Hemotherapy of Pernambuco (HEMOPE) were interviewed regarding socioeconomic, sociodemographic, and behavioral data and analyzed for anti-HEV IgG. Anti-HEV IgG was detected using the HEV IgG (EUROIMMUN) kit. Associations between seropositivity and potential risk factors were analyzed by the χ2 test and Fisher's exact test. Seroprevalence was 0.9% (9/996), 77.77% (7/9) and 22.22% (2/9) in blood donors and donor candidates, respectively. HEV seropositivity was associated with male (OR: 11.65; CI: 0.6755-200.9; p = 0.0163), income higher than BRL 20,000/month (p = 0.0002), and lake bathing (OR: 4.553; CI: 1.391-15.25; p = 0.0258). Importantly, about 43% (3/7) of anti-HEV positive donors made their first donation more than 20 years ago, which must be taken as a warning sign, given the possibility that these individuals may have been infected after registration as donors. Finally, the report of HEV seropositivity, especially in regular blood donors, as well as the identification of potential risk factors, reinforces the need for viral screening in Brazilian blood banks.

Long-Term Persistence of Serum-Specific Anti-Chikungunya IgM Antibody - A Case Series of Brazilian Patients.

The persistence of serum-specific anti-chikungunya IgM antibodies (CHIKV-IgM) can vary after chikungunya fever (CHIK) infection. However, the factors related to its production are not yet known. We described a case series drawn up from data collected from 57 patients between 12 and 36 months after the acute phase of CHIK infection in Northeastern Brazil. CHIKV-IgM was detectable in 7/57 (12.3%) patients after 28.3 months of infection. No frequency differences in chronic musculoskeletal manifestations and underlying conditions were detected between patients with or without CHIKV-IgM. CHIKV-IgM was detected for up to 35 months in Brazilian patients after CHIK infection.

Evaluation of IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ cytokines in HIV/HHV-8 coinfection.

Imbalance in the immune response is one of the main pathogenic mechanisms of diseases related with human immunodeficiency virus (HIV)/human gammaherpesvirus 8 (HHV-8) coinfection, such as Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), multicentric Castleman disease (MCD) and the Kaposi's sarcoma-associated herpesvirus inflammatory cytokine syndrome (KICS). However, significant changes in pro- and anti-inflammatory cytokine levels may be observed in HIV/HHV-8 individuals who are negative for KS, PEL, MCD, and/or KICS. In this study, serum levels of interleukin-2 (IL-2), IL-4, IL-6, IL-10, tumor nucrosis factor α (TNF-α) and interferon γ (IFN-γ) were assessed in 69 HIV and 48 HIV/HHV-8 individuals, all negatives for HHV-8-related diseases. The cytokines were measured by flow cytometry and analyzed by the Mann-Whitney test. The p < .05 and 95% confidence interval were considered in all analyzes. IL-4 (p = .0155), IL-6 (p = .0036), and IL-10 (p = .0036) levels were significantly higher in HIV/HHV-8 patients than in the HIV group. On the other hand, IL-2 (p = .2295), TNF-α (p = .1216) and IFN-γ (p = .1178) did not differ between the groups analyzed. To our knowledge, to date, this is the first report on significant differences in the levels of IL-4 and IL-6 in HIV versus HIV/HHV-8 individuals. Finally, these early findings are important as a prognostic tool and contribute to clarifying the HHV-8-host interaction.

Risk analysis and seroprevalence of HEV in people living with HIV/AIDS in Brazil.

Acute Hepatitis E virus (HEV) infection in people living with HIV/AIDS (PLHA) can lead to fulminant hepatic failure, cirrhosis and death. The prevalence of anti-HEV antibodies within this group varies according to the geographical area. However, in South America, studies concerning the detection of HEV in PLHA are rare. Here, we investigated the presence of HEV by serological and molecular detection and evaluated the risk factors associated with infection in PLHA in Pernambuco state, Brazilian Northeast. Serological and molecular detection of HEV was performed in 366 samples of PLHA by ELISA for anti-HEV IgG and RT-PCR, respectively. Anti-HEV IgG prevalence was 4.1% (15/366) and no HEV RNA was detected. Concerning the risk factors, we evaluated, in multivariable analysis, age, years of school, sexual orientation, oral-anal sex, use of injectable drugs and piped water. Among them, only piped water availability could be associated with the HEV infection in PLHA (OR: 0.08; CI 95%: 0.01-0.66; p = 0.0182). This study showed for the first time the association of piped water as protection factor for HEV infection in PLHA. Finally, this is also the first report of HEV seroprevalence in PLHA in the Northeast Brazil.