Different profiles of chemokines, cytokines and cell growth factors in plasma samples from patients with leprosy, leprosy reactions and households contacts.

BACKGROUND: Leprosy is a highly neglected disease that is considered a serious public health problem in many countries. This illness is characterised by a variety of clinical and histopathological manifestations that are related to the patient immune response. OBJECTIVES: This work aimed evaluate the profile of circulating immune mediators in the plasma from patients classified clinically as paucibacillary (PB), multibacillary (MB), households contacts (HHC), type1 leprosy reaction (T1R), type2 leprosy reaction (T2R) and control individuals without medical history of leprosy (CTL). METHODS: To assessment of the plasma immune mediators was used multiplex microbeads immunoassay "Luminex". FINDINGS: The results showed that patients (PB) had a regulatory-biased profile, while MB revealed a pro-inflammatory trend of highly expressed biomarkers. HHC display conspicuously increased levels in the plasma of the chemokines (CCL2, CCL3, CCL4, CCL5 and CXCL8), pro-inflammatory cytokines (IFN-γ,TNF and IL-1ß), modulating cytokines (IL-9 and IL-1Ra) and growth factors (PDGF, G-CSF and IL-2). Interestingly, HHC displayed superior production of IFN-γ as compared to other leprosy groups, indicating a putative protective role for this cytokine during chronic Mycobacterium leprae exposure. MAIN CONCLUSION: Further investigations are currently underway to elucidate the potential of these mediators as biomarkers applicable to the diagnosis/prognosis of leprosy and also T1R and T2R leprosy reactions.

Serum soluble mediators as prognostic biomarkers for morbidity, disease outcome, and late-relapsing hepatitis in yellow fever patients.

This study described a soluble mediator storm in acute Yellow Fever/YF infection along the kinetics timeline towards convalescent disease. The analyses of the YF Viral RNAnemia, chemokines, cytokines, and growth factors were performed in YF patients at acute/(D1-15) and convalescent/(D16-315) phases. Patients with acute YF infection displayed a trimodal viremia profile spreading along D3, D6, and D8-14. A massive storm of mediators was observed in acute YF. Higher levels of mediators were observed in YF with higher morbidity scores, patients under intensive care, and those progressing to death than in YF patients who progress to late-relapsing hepatitis/L-Hep. A unimodal peak of biomarkers around D4-6 with a progressive decrease towards D181-315 was observed in non-L-Hep patients, while a bimodal pattern with a second peak around D61-90 was associated with L-Hep. This study provided a comprehensive landscape of evidence that distinct immune responses drive pathogenesis, disease progression, and L-Hep in YF patients.

Plasma immune mediators as laboratorial biomarkers for Sickle Cell Disease patients according to the hydroxyurea therapy and disease severity.

In the present work, the impact of Sickle Cell Disease (SCD) degrees of severity, as well hydroxyurea treatment on the systemic immunological signatures of patients was evaluated. Based on a high-throughput chemokine, cytokine and growth factor multiplex analysis, it was possible to obtain the systemic immunological profile of patients with SCD (n = 40), treated or not with hydroxyurea, as compared to healthy controls (n = 40). Overall, SCD patients with severe disease displayed increased levels of almost all biomarkers analyzed. Our data demonstrated that CXCL8, CCL3 and CXCL10 were pointed out as universal biomarkers of SCD. The results also indicated that HU-untreated patients with indication of HU-therapy display a more prominent increase on plasma immune mediators in a similar way as those with severe SCD disease. Together, these findings provided a comprehensive landscape of evidence that may have implications for further therapeutic strategies and SCD clinical management.

The neurotoxic branch of the kynurenine pathway is highly activated in the central nervous system of patients with pneumococcal meningitis.

BACKGROUND: Acute bacterial meningitis (ABM) causes excessive activation of N-methyl-D-aspartate receptors (NMDAr), leading to cortical and hippocampal neuron death. As opposite, enteroviral meningitis is more frequently benign. The kynurenine (KYN) pathway is the major catabolic route of tryptophan (TRP) and some of its metabolites are agonists or antagonists of NMDAr. METHODS: In order to investigate the pathogen-specific patterns of KYN pathway modulation in the central nervous system of children with acute meningococcal (MM), pneumococcal (PM) or enteroviral (VM) meningitis, the cerebrospinal fluid (CSF) concentrations of TRP, KYN, kynurenic acid (KYNA) and quinolinic acid (QUINA) were evaluated by ultra-high performance liquid chromatography (uHPLC) coupled to mass spectrometry. In addition, CSF levels of IL-6, IL-10 and TNF-α were quantified by multi-analyte flow assay. The data was mined and integrated using statistical and machine learning methods. RESULTS: The three forms of meningitis investigated herein up-regulated the neurotoxic branch of the KYN pathway within the intrathecal space. However, this response, represented by the concentration of QUINA, was six and nine times higher in PM patients compared to MM or VM, respectively. CSF levels of IL-6, TNF-α, and IL-10 were increased in MM and PM patients when compared to controls. In VM, CSF IL-6 and IL-10, but not TNF-α were increased compared to controls, although not reaching the high levels found in bacterial meningitis. No correlation was found between the concentrations or the ratios of any pair of KYN metabolites and any cytokine or standard cytochemical parameter tested. CONCLUSIONS: CNS infection with meningococci, pneumococci, and enteroviruses intrathecally activate the KYN pathway, favoring its neurotoxic branch. However, in PM, higher CSF levels of QUINA, compared to MM and VM, may contribute to its poorer neurologic outcome.

Serum biomarkers in patients with unilateral or bilateral active pulmonary tuberculosis: Immunological networks and promising diagnostic applications.

The present observational study was designed to characterize the integrative profile of serum soluble mediators to describe the immunological networks associated with clinical findings and identify putative biomarkers for diagnosis and prognosis of active tuberculosis. The study population comprises 163 volunteers, including 84 patients with active pulmonary tuberculosis/(TB), and 79 controls/(C). Soluble mediators were measured by multiplexed assay. Data analysis demonstrated that the levels of CCL3, CCL5, CXCL10, IL-1ß, IL-6, IFN-γ, IL-1Ra, IL-4, IL-10, PDGF, VEGF, G-CSF, IL-7 were increased in TB as compared to C. Patients with bilateral pulmonary involvement/(TB-BI) exhibited higher levels of CXCL8, IL-6 and TNF with distinct biomarker signatures (CCL11, CCL2, TNF and IL-10) as compared to patients with unilateral infiltrates/(TB-UNI). Analysis of biomarker networks based in correlation power graph demonstrated small number of strong connections in TB and TB-BI. The search for biomarkers with relevant implications to understand the pathogenetic mechanisms and useful as complementary diagnosis tool of active TB pointed out the excellent performance of single analysis of IL-6 or CXCL10 and the stepwise combination of IL-6 â†’ CXCL10 (Accuracy = 84 %; 80 % and 88 %, respectively). Together, our finding demonstrated that immunological networks of serum soluble biomarkers in TB patients differ according to the unilateral or bilateral pulmonary involvement and may have relevant implications to understand the pathogenetic mechanisms involved in the clinical outcome of Mtb infection.

Yellow Fever Molecular Diagnosis Using Urine Specimens during Acute and Convalescent Phases of the Disease.

Prior studies have demonstrated prolonged presence of yellow fever virus (YFV) RNA in saliva and urine as an alternative to serum. To investigate the presence of YFV RNA in urine, we used RT-PCR for YFV screening in 60 urine samples collected from a large cohort of naturally infected yellow fever (YF) patients during acute and convalescent phases of YF infection from recent YF outbreaks in Brazil (2017 to 2018). Fifteen urine samples from acute phase infection (up to 15 days post-symptom onset) and four urine samples from convalescent phase infection (up to 69 days post-symptom onset), were YFV PCR-positive. We genotyped YFV detected in seven urine samples (five collected during the acute phase and two collected during the YF convalescent phase). Genotyping indicated the presence of YFV South American I genotype in these samples. To our knowledge, this is the first report of wild-type YFV RNA detection in the urine this far out from symptom onset (up to 69 DPS), including YFV RNA detection during the convalescent phase of YF infection. The detection of YFV RNA in urine is an indicative of YFV infection; however, the results of RT-PCR using urine as sample should be interpreted with care, since a negative result does not exclude the possibility of YFV infection. With a possible prolonged period of detection beyond the viremic phase, the use of urine samples coupled with serological tests, epidemiologic inquiry, and clinical assessment could provide a longer diagnostic window for laboratory YF diagnosis.

Chagasic cardiomyopathy is marked by a unique signature of activated CD4+ T cells.

Chagas disease is a neglected tropical disease in Latin America and an imported emerging disease worldwide. Chronic Chagas disease cardiomyopathy (CCC) is the most prominent clinical form and can lead to heart failure, thromboembolism, and sudden death. While previous reports have supported a role for CD4+ T lymphocytes in the pathogenesis of CCC a comprehensive analysis of these cells during different clinical forms is lacking. Here, we used high-dimensional flow cytometry to assess the diversity of circulating CD4+ T cells in patients with distinct clinical forms. We found increased frequencies of CD4+CD69+ T cells in patients compared to controls. CD39+ regulatory T cells, represented by mesocluster 6 were reduced in mild CCC patients compared to controls. Cytotoxic CD4+ T cells co-expressing granzyme B and perforin were expanded in patients with Chagas disease and were higher in patients with mild CCC compared to controls. Furthermore, patients with mild CCC displayed higher frequencies of multifunctional effector memory CD4+ T cells. Our results demonstrate an expansion in activated CD4+ T cells and a decrease in a functional subset of regulatory T cells associated with the onset of Chagas cardiomyopathy, suggesting their role in the establishment of cardiac lesions and as potential biomarkers for disease aggravation.

Acute kidney injury associated to COVID-19 leads to a strong unbalance of circulant immune mediators.

BACKGROUND: Severe cases of coronavirus disease 2019 (COVID-19) have increased risk for acute kidney injury (AKI). The exacerbation of the immune response seems to contribute to AKI development, but the immunopathological process is not completely understood. OBJECTIVES: To analyze levels of circulant immune mediators in COVID-19 patients evolving with or without AKI. We have also investigated possible associations of these mediators with viral load and clinical outcomes. METHODS: This is a longitudinal study performed with hospitalized patients with moderate to severe COVID-19. Serum levels of 27 immune mediators were measured by a multiplex immunoassay. Data were analyzed at two timepoints during the follow-up: within the first 13 days of the disease onset (early sample) and from the 14th day to death or hospital discharge (follow-up sample). RESULTS: We studied 82 COVID-19 patients (59.5 ± 17.5 years, 54.9% male). Of these, 34 (41.5%) developed AKI. These patients presented higher SARS-CoV-2 viral load (P = 0.03), higher frequency of diabetes (P = 0.01) and death (P = 0.0004). Overall, AKI patients presented significantly higher and sustained levels (P < 0.05) of CCL-2, CCL-3, CCL-4, CXCL-8, CXCL-10, IFN-γ, IL-2, IL-6, TNF-α, IL-1Ra, IL-10 and VEGF. Importantly, higher levels of CCL-2, CXCL-10, IL-2, TNF-α, IL-10, FGFb, and VEGF were observed in AKI patients independently of death. ROC curves demonstrated that early alterations in CCL-2, CXCL-8, CXCL-10, IFN-γ, IL-6, IL-1Ra and IL-10 show a good predictive value regarding AKI development. Lastly, immune mediators were significantly associated with each other and with SARS-CoV-2 viral load in AKI patients. CONCLUSIONS: COVID-19 associated AKI is accompanied by substantial alterations in circulant levels of immune mediators, which could significantly contribute to the establishment of kidney injury.

Cognitive Frailty is Associated With Elevated Proinflammatory Markers and a Higher Risk of Mortality.

BACKGROUND: Cognitive impairment and physical frailty are common among older adults and associated with a higher likelihood of adverse health outcomes. These two conditions frequently coexist in the same individual as cognitive frailty, yet few studies have examined the impact of such comorbidity on clinical outcomes or underlying biological mechanisms. METHODS: A total of 1,340 older adults (age ≥60 years old) from the Bambui Cohort Study of Ageing, with a total follow-up of 10 years, were included in this study. Frailty was defined by the accumulation of deficit framework and cognitive impairment based on scores on the MMSE less than 22. In addition, serum IL-6 levels were measured by cytometric bead array assay. RESULTS: Individuals classified with cognitive frailty had significantly higher serum IL-6 levels compared to the robust, cognitively unimpaired group. Those with cognitive frailty (aOR = 1.97 [1.18-3.27] and prefrailty and cognitive impairment (aOR = 1.83 [1.24-2.69]) had the highest mortality risk over 10 years of follow-up. Higher IL-6 levels were also independently associated with a higher mortality rate (aOR = 1.37 [1.23-1.54]). CONCLUSION: Our study shows that cognitive Frailty indicates a vulnerability state and of increasing mortality risk. Our findings also suggested that proinflammatory abnormalities can be viewed as a central phenomenon underlying common age-related problems (e.g., cognitive impairment and Frailty) and outcomes (e.g., mortality).

Long-term impact of congenital toxoplasmosis on phenotypic and functional features of circulating leukocytes from infants one year after treatment onset.

Changes in immune response of children with congenital toxoplasmosis (CT) regarding infection evolution and therapeutic intervention was addressed. Infants with CT presented increased counts of monocytes, CD3-CD16-CD56High, CD3+CD56+ and CD4+ T-cells 1-year after treatment onset (TOXO1-yearAT). Smaller numbers of CD3-CD16-CD56+ and TCRγδ+ T-cells were specifically observed in infants with retinochoroidal lesions (L(+)). When infants were classified based on the baseline status, expansion of CD3-CD16-CD56High and CD4+ T-cells were observed in L(+) who had active, active/cicatricial or cicatricial lesions. Infants who had active or active/cicatricial lesions display augmented numbers of monocytes, CD3-CD16+CD56+, CD3+CD56+, CD8+DR+ and TCRγδ+ T-cells and those with active/cicatricial or cicatricial at baseline displayed increase in CD14+CD64+ monocytes. Moreover, all L(+) had increased IFN-γ+ and IL-10+ CD4+ T-cells, while L(-) had increased ratios of TNF+, IFN-γ+ and IL-4+ NK-cells upon antigen-specific stimulation. Persistent alterations in leukocytes in TOXO1-yearAT suggest long-term sequels in the immune system of infants with CT.

Chemokines in Leishmaniasis: Map of cell movements highlights the landscape of infection and pathogenesis.

Pathogen interactions with the host immune response components are critical for establishing protective immunity and pathological responses against Leishmania parasites. A predominant proinflammatory profile associated with enhanced phagocytosis trigger a cell-mediated immune response that is relevant to infection control. On the other hand, an anti-inflammatory phenotype, correlated with a predominant modulated/regulatory response, favors intracellular proliferation of Leishmania parasites and disease progression. In this context, chemokines play an important role in determining cellular composition at inflammatory sites. Leishmania infection induces the expression of various chemokines and chemokine receptors in the mammalian host, which can subvert the host immune responses. Indeed, the balance and dynamic changes in cytokines and chemokines may control or predict the disease outcome. In this review, we address our current knowledge regarding the chemokines and chemokines receptors' role in the immunopathogenesis of Tegumentary and Visceral Leishmaniasis.

Addition of caffeine to equine thawed sperm increases motility and decreases nitrite concentration.

The aim of this study was to improve the quality of frozen-thawed equine sperm by the addition of caffeine to it. Semen from nine stallions was frozen and different concentrations of caffeine (3, 5 and 7.5 mM) were added to frozen-thawed semen. The sperm kinetic parameters, membrane functionality and integrity, and acrosome integrity and spontaneous acrosome reacted sperm were evaluated with a computer-assisted sperm analysis, a hypoosmotic swelling test and epifluorescent microscopy, respectively. Nitrite and hydroperoxide concentrations of frozen-thawed semen were measured using spectrophotometry. Sperm fertility was evaluated by artificial insemination (AI) of 16 mares with thawed ejaculates (control and 5 mM caffeine-treated groups). Compared to that in the control, the addition of 5 mM caffeine induced an increase in sperm motility (38.9 ± 2.8 versus 32.6 ± 3.4%), and a decrease in nitrite concentration (11.4 ± 2.1 versus 12.8 ± 2.9 µM/µg protein, p < .05). Moreover, the pregnancy rate from AI in the caffeine group was significantly higher (62.5%) than that in the control group (12.5%). These data suggest that caffeine reduced the nitrite concentration and enhanced sperm motility in thawed equine sperm, thus increasing the fertility rate in mares inseminated with caffeine-treated equine semen.

Validation of a yellow fever vaccine model using data from primary vaccination in children and adults, re-vaccination and dose-response in adults and studies with immunocompromised individuals.

BACKGROUND: An effective yellow fever (YF) vaccine has been available since 1937. Nevertheless, questions regarding its use remain poorly understood, such as the ideal dose to confer immunity against the disease, the need for a booster dose, the optimal immunisation schedule for immunocompetent, immunosuppressed, and pediatric populations, among other issues. This work aims to demonstrate that computational tools can be used to simulate different scenarios regarding YF vaccination and the immune response of individuals to this vaccine, thus assisting the response of some of these open questions. RESULTS: This work presents the computational results obtained by a mathematical model of the human immune response to vaccination against YF. Five scenarios were simulated: primovaccination in adults and children, booster dose in adult individuals, vaccination of individuals with autoimmune diseases under immunomodulatory therapy, and the immune response to different vaccine doses. Where data were available, the model was able to quantitatively replicate the levels of antibodies obtained experimentally. In addition, for those scenarios where data were not available, it was possible to qualitatively reproduce the immune response behaviours described in the literature. CONCLUSIONS: Our simulations show that the minimum dose to confer immunity against YF is half of the reference dose. The results also suggest that immunological immaturity in children limits the induction and persistence of long-lived plasma cells are related to the antibody decay observed experimentally. Finally, the decay observed in the antibody level after ten years suggests that a booster dose is necessary to keep immunity against YF.

Amlodipine Increases the Therapeutic Potential of Ravuconazole upon Trypanosoma cruzi Infection.

Mining existing agents that enhance the therapeutic potential of ergosterol biosynthesis inhibitors (EBI) is a promising approach to improve Chagas disease chemotherapy. In this study, we evaluated the effect of ravuconazole, an EBI, combined with amlodipine, a calcium channel blocker, upon Trypanosoma cruzi experimental infection. In vitro assays confirmed the trypanocidal activity of both compounds in monotherapy and demonstrated an additive effect (sum of the fractional inhibitory concentration [ΣFIC] > 0.5) of the combined treatment without additional toxicity to host cells. In vivo experiments, using a murine model of the T. cruzi Y strain in a short-term protocol, demonstrated that amlodipine, although lacking trypanocidal activity, dramatically increased the antiparasitic activity of underdosing ravuconazole regimens. Additional analysis using long-term treatment (20 days) showed that parasitemia relapse until 60 days after treatment was significatively lower in mice treated with the combination (4 out of 14 mice) than ravuconazole monotherapy (10 out of 14 mice), even in the presence of immunosuppressant pressure. Furthermore, the combined therapy was well tolerated and protected the mice from mortality. The treatments also impacted on the cellular and humoral immune response of infected animals, inducing a reduction of serum cytokine levels in all ravuconazole-treated mice. Our findings demonstrate that amlodipine is efficacious in enhancing the antiparasitic activity of ravuconazole in an experimental model of T. cruzi infection and indicates a potential strategy to be explored in Chagas disease treatment.

Prospection of immunological biomarkers for characterization and monitoring of asymptomatic Leishmania (Leishmania) infantum infection.

In areas endemic for Leishmania infantum, an asymptomatic infection may be an indicator of the extent of transmission. The main goal of this study was to evaluate the applicability of measuring circulating immunological biomarkers as an alternative strategy to characterize and monitor L. infantum asymptomatic infections in combination with serological methods. To this end, 179 children from a region endemic for visceral leishmaniasis (VL), aged 1-10 years old, selected from a cross-sectional study, were identified as asymptomatic (n = 81) or uninfected (n = 98) by qPCR and/or serological tests (ELISA using L. infantum soluble antigen and rK39), and, together with serum samples of children diagnosed with VL (n = 43), were subjected to avidity tests and cytokine levels measurement. Avidity rates (AR) ranging from 41 to 70% were found in 29 children (66%) from the asymptomatic group. On the other hand, high AR (above 70%) were observed in 27 children (64%) from the VL group. Logistic Regression and Classification and Regression Tree (CART) analyses demonstrated that lower AR and IFN-γ production associated with higher IL-17A levels were hallmarks in asymptomatic L. infantum infections. Therefore, this study proposes an association of immunological biomarkers that can be used as a complementary strategy for the characterization and monitoring of asymptomatic VL infections in children living in endemic areas.

Toxoplasma gondii: Cytokine responses in mice reinfected with atypical strains.

This study aimed to elucidate the cellular immune response against Toxoplasma gondii in chronically infected mice reinfected with different strains of the parasite to elucidate the immunological basis for chronicity or virulence and to uncover the involvement of genes that encode virulence proteins and modulate the immune response. BALB/c mice were infected by oral gavage with non-virulent D8 strain and challenged 45 days post-infection with virulent EGS or CH3 strains. Cytokine measurement was performed 2 days post-challenge in cell extracts of the small intestine and 2, 7, and 14 days post-challenge in serum. Virulence gene allele type of these strains was analyzed. Challenged mice survived by avoiding exacerbated inflammation and inhibiting the overproduction of cytokines. Local and systemic cytokine response in challenged mice was similar to chronic controls and quite distinct in mice acutely infected with the EGS or CH3 strains. Allelic combinations of the virulence genes ROP5/ROP18 was predictive of virulence in mice when tested in these T. gondii strains. Other allelic combinations of rhoptries and dense granules genes showed discrepancies.

Leishmania infantum induces high phagocytic capacity and intracellular nitric oxide production by human proinflammatory monocyte.

BACKGROUND: The mechanism of resistance to SbIII in Leishmania is complex, multifactorial and involves not only biochemical mechanisms, but also other elements, such as the immune system of the host. OBJECTIVES: In this study, putative changes in the immunological profile of human monocytes infected with wild-type (WT) and antimony (SbIII)-resistant Leishmania (Viannia) braziliensis and Leishmania (Leishmania) infantum lines were evaluated. METHODS: Susceptibility assays WT and SbIII-resistant L. braziliensis and L. infantum were performed using lines THP-1 human monocytic lineage. Phagocytic capacity, cytokine profile, intracellular nitric oxide (NO) production and surface carbohydrate residues profile were performed in peripheral blood monocytes by flow cytometry. FINDINGS: The phagocytic capacity and intracellular NO production by classical (CD14++CD16-) and proinflammatory (CD14++CD16+) monocytes were higher in the presence of L. infantum lines compared to L. braziliensis lines. The results also highlight proinflammatory monocytes as the cellular subpopulation of major relevance in a phagocytosis event and NO expression. It is important to note that L. infantum induced a proinflammatory cytokine profile characterised by higher levels of TNF-α in culture supernatant than L. braziliensis. Conversely, both Leishmania lines induce high levels of IL-6 in culture supernatant. Analysis of the expression profile of surface carbohydrates showed that L. braziliensis presents 4.3-fold higher expression of galactose(ß1,4)N-acetylglucosamine than L. infantum line. Interestingly, the expression level of α-N-acetylgalactosamine residues was 2-fold lower in the SbIII-resistant L. braziliensis line than its counterpart WT line, indicating differences in surface glycoconjugates between these lines. MAIN CONCLUSIONS: Our results showed that L. braziliensis and L. infantum induce different innate immune responses and a highly inflammatory profile, which is characteristic of infection by L. infantum, the species associated with visceral disease.

Increased platelet distribution width and reduced IL-2 and IL-12 are associated with thrombocytopenia in Plasmodium vivax malaria.

BACKGROUND: Thrombocytopenia in malaria involves platelet destruction and consumption; however, the cellular response underlying this phenomenon has still not been elucidated. OBJECTIVE: To find associations between platelet indices and unbalanced Th1/Th2/Th17 cytokines as a response to thrombocytopenia in Plasmodium vivax infected (Pv-MAL) patients. METHODS: Platelet counts and quantification of Th1/Th2/Th17 cytokine levels were compared in 77 patients with uncomplicated P. vivax malaria and 37 healthy donors from the same area (endemic control group - ENCG). FINDINGS: Thrombocytopenia was the main manifestation in 55 patients, but was not associated with parasitaemia. The Pv-MAL patients showed increases in the mean platelet volume (MPV), which may be consistent with larger or megaplatelets. Contrary to the findings regarding the endemic control group, MPV and platelet distribution width (PDW) did not show an inverse correlation, due the increase in the heterogeneity of platelet width. In addition, the Pv-MAL patients presented increased IL-1ß and reduced IL-12p70 and IL-2 serum concentrations. Furthermore, the reduction of these cytokines was associated with PDW values. MAIN CONCLUSIONS: Our data demonstrate that an increase in MPV and the association between reductions of IL-2 and IL-12 and PDW values may be an immune response to thrombocytopenia in uncomplicated P. vivax malaria.

The association of cognitive performance and IL-6 levels in schizophrenia is influenced by age and antipsychotic treatment.

Aims: Recent findings suggest that cognitive impairment can be associated with inflammation and immune changes in schizophrenia. We aimed to study possible associations between cytokine levels and cognitive performance in a sample of patients with schizophrenia.Methods: Cognition was assessed with the brief assessment of cognition in schizophrenia in 63 clinically stable outpatients with schizophrenia. Blood was collected and cytokines (IL-2, IL-4, IL-6, IL-10, IL-17A, TNF-α, IFN-γ) were measured by cytometric bead array method. Psychopathological scales were also applied.Results: IL-6 correlated negatively with general cognitive performance (rho = -0.395, p = .017) and positively with antipsychotic dose (rho = 0.412, p = .004). Multiple regression analysis showed that cognitive performance is associated with age and antipsychotic dose (p = .000 and p = .033).Conclusion: The association between IL-6 levels and cognitive performance is dependent on age and antipsychotic dose.

17DD Yellow Fever Revaccination and Heightened Long-Term Immunity in Populations of Disease-Endemic Areas, Brazil.

We evaluated the duration of neutralizing antibodies and the status of 17DD vaccine-specific T- and B-cell memory following primary and revaccination regimens for yellow fever (YF) in Brazil. We observed progressive decline of plaque-reduction neutralization test (PRNT) seropositivity and of the levels of effector memory CD4+ and CD8+ T cells, as well as interferon-γ+CD8+ T cells, 10 years after primary vaccination. Revaccination restored PRNT seropositivity as well as the levels of effector memory CD4+, CD8+, and interferon-γ+CD8+ T cells. Moreover, secondary or multiple vaccinations guarantee long-term persistence of PRNT positivity and cell-mediated memory 10 years after booster vaccination. These findings support the relevance of booster doses to heighten the 17DD-YF-specific immune response to guarantee the long-term persistence of memory components. Secondary or multiple vaccinations improved the correlates of protection triggered by 17DD-YF primary vaccination, indicating that booster regimens are needed to achieve efficient immunity in areas with high risk for virus transmission.