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Zika virus infection is associated with the development of Guillain-Barré syndrome (GBS), a neurological autoimmune disorder caused by immune recognition of gangliosides and other components at nerve membranes. Using a high-throughput ELISA, we have analyzed the anti-glycolipid antibody profile, including gangliosides, of plasma samples from patients with Zika infections associated or not with GBS in Salvador, Brazil. We have observed that Zika patients that develop GBS present higher levels of anti-ganglioside antibodies when compared to Zika patients without GBS. We also observed that a broad repertoire of gangliosides was targeted by both IgM and IgG anti-self antibodies in these patients. Since Zika virus infects neurons, which contain membrane gangliosides, antigen presentation of these infected cells may trigger the observed autoimmune anti-ganglioside antibodies suggesting direct infection-induced autoantibodies as a cause leading to GBS development. Collectively, our results establish a link between anti-ganglioside antibodies and Zika-associated GBS in patients. [ABSTRACT FROM AUTHOR]

Background: The Plasmodium vivax Reticulocyte Binding Protein (PvRBP) family is involved in red blood cell recognition and members of this family are potential targets for antibodies that may block P. vivax invasion. To date, the acquisition of immunity against PvRBPs in low malaria transmission settings and in a broad age group of exposed individuals has not been investigated. Methodology/Principal findings: Total IgG antibody levels to six members of the PvRBP family (PvRBP1a, PvRBP1b, PvRBP2a, PvRBP2b, a non-binding fragment of PvRBP2c (PvRBP2cNB) and PvRBP2-P2) were measured in samples collected from individuals living in two regions of low P. vivax endemicity in Brazil and Thailand. In both settings, levels of total IgG to PvRBP1a, PvRBP2b, PvRBP2cNB, and PvRBP2P-2 increased significantly with age (rho = 0.17–0.49; P<0.001). IgG responses to PvRBP1a, PvRBP2b and PvRBP2cNB were significantly higher in infected individuals by using Wilcoxon’s signed-rank test (P<0.001). Of the six PvRBPs examined, only antibodies to PvRBP2b were associated with protection against clinical malaria in both settings. Conclusion/Significance: Our results indicate that PvRBP2b warrants further preclinical development as a blood-stage vaccine candidate against P. vivax. Total IgG responses to PvRBPs were also shown to be promising immunological markers of exposure to P. vivax infection. [ABSTRACT FROM AUTHOR]

Objective: To investigate the association between maternal anemia and low/insufficient birth weight. Design: A prospective cohort study of pregnant women who underwent prenatal care at the healthcare units in a municipality of northeast Brazil together with their newborn infants was carried out. The pregnant women were classified as having anemia when the hemoglobin level was below 11 g/dl. Infants who were born full term weighing less than 2500 grams were classified as low birth weight, and those weighing between 2500 and 2999 grams were classified as insufficient weight. The occurrence of maternal anemia and its association with birth weight was verified using crude and adjusted Relative Risk (RR) estimates with their corresponding 95% confidence intervals (95%CIs). Results: The final sample was comprised of 622 women. Maternal anemia was considered a risk factor for low/insufficient birth weight, after adjusting the effect measurement for maternal age, family income, urinary infection, parity, alcoholic beverage consumption during pregnancy and gestational body mass index: RRadjusted = 1.38 [95% CI: 1.07 to 1.77]. Conclusions: Maternal anemia was associated with low/insufficient birth weight, representing a risk factor for the gestational outcomes studied. [ABSTRACT FROM AUTHOR]

Background: Despite decades of use of control programs, schistosomiasis remains a global public health problem. To further reduce prevalence and intensity of infection, or to achieve the goal of elimination in low-endemic areas, there needs to be better diagnostic tools to detect low-intensity infections in low-endemic areas in Brazil. The rationale for development of new diagnostic tools is that the current standard test Kato-Katz (KK) is not sensitive enough to detect low-intensity infections in low-endemic areas. In order to develop new diagnostic tools, we employed a proteomics approach to identify biomarkers associated with schistosome-specific immune responses in hopes of developing sensitive and specific new methods for immunodiagnosis. Methods and findings: Immunoproteomic analyses were performed on egg extracts of Schistosoma mansoni using pooled sera from infected or non-infected individuals from a low-endemic area of Brazil. Cross reactivity with other soil-transmitted helminths (STH) was determined using pooled sera from individuals uniquely infected with different helminths. Using this approach, we identified 23 targets recognized by schistosome acute and chronic sera samples. To identify immunoreactive targets that were likely glycan epitopes, we compared these targets to the immunoreactivity of spots treated with sodium metaperiodate oxidation of egg extract. This treatment yielded 12/23 spots maintaining immunoreactivity, suggesting that they were protein epitopes. From these 12 spots, 11 spots cross-reacted with sera from individuals infected with other STH and 10 spots cross-reacted with the negative control group. Spot number 5 was exclusively immunoreactive with sera from S. mansoni-infected groups in native and deglycosylated conditions and corresponds to Major Egg Antigen (MEA). We expressed MEA as a recombinant protein and showed a similar recognition pattern to that of the native protein via western blot. IgG-ELISA gave a sensitivity of 87.10% and specificity of 89.09% represented by area under the ROC curve of 0.95. IgG-ELISA performed better than the conventional KK (2 slides), identifying 56/64 cases harboring 1–10 eggs per gram of feces that were undiagnosed by KK parasitological technique. Conclusions: The serological proteome approach was able to identify a new diagnostic candidate. The recombinant egg antigen provided good performance in IgG-ELISA to detect individuals with extreme low-intensity infections (1 egg per gram of feces). Therefore, the IgG-ELISA using this newly identified recombinant MEA can be a useful tool combined with other techniques in low-endemic areas to determine the true prevalence of schistosome infection that is underestimated by the KK method. Further, to overcome the complexity of ELISA in the field, a second generation of antibody-based rapid diagnostic tests (RDT) can be developed. [ABSTRACT FROM AUTHOR]

Laboratory confirmation of Zika virus (ZIKV) infection during pregnancy is challenging due to cross-reactivity with dengue virus (DENV) and limited knowledge about the kinetics of anti-Zika antibody responses during pregnancy. We described ZIKV and DENV serological markers and the maternal-fetal transfer of antibodies among mothers and neonates after the ZIKV microcephaly outbreak in Northeast Brazil (2016). We included 89 microcephaly cases and 173 neonate controls at time of birth and their mothers. Microcephaly cases were defined as newborns with a particular head circumference (2 SD below the mean). Two controls without microcephaly were matched by the expected date of delivery and area of residence. We tested maternal serum for recent (ZIKV genome, IgM and IgG3 anti-NS1) and previous (ZIKV and DENV neutralizing antibodies [NAbs]) markers of infection. Multiple markers of recent or previous ZIKV and DENV infection in mothers were analyzed using principal component analysis (PCA). At delivery, 5.6% of microcephaly case mothers and 1.7% of control mothers were positive for ZIKV IgM. Positivity for ZIKV IgG3 anti-NS1 was 8.0% for case mothers and 3.5% for control mothers. ZIKV NAbs was slightly higher among mothers of cases (69.6%) than that of mothers of controls (57.2%; p = 0.054). DENV exposure was detected in 85.8% of all mothers. PCA discriminated two distinct components related to recent or previous ZIKV infection and DENV exposure. ZIKV NAbs were higher in newborns than in their corresponding mothers (p<0.001). We detected a high frequency of ZIKV exposure among mothers after the first wave of the ZIKV outbreak in Northeast Brazil. However, we found low sensitivity of the serological markers to recent infection (IgM and IgG3 anti-NS1) in perinatal samples of mothers of microcephaly cases. Since the neutralization test cannot precisely determine the time of infection, testing for ZIKV immune status should be performed as early as possible and throughout pregnancy to monitor acute Zika infection in endemic areas. [ABSTRACT FROM AUTHOR]

Background: Arterial stiffness has been associated with renal dysfunction and its progression, but the pathophysiological relation underlying this association has not been fully established, particularly among individuals without hypertension and diabetes. We investigated the cross-sectional associations between arterial stiffness and renal function in adults without cardiovascular disease, and whether this association remained among subjects without hypertension and diabetes. Methods: All eligible participants from ELSA-Brasil (2008–2010), aged 35 to 74 years (N = 13,586) were included, of whom 7,979 were free from hypertension and diabetes. The response variables were: 1) low glomerular filtration rate (eGFR<60ml/min/1.73m2) estimated by CKD-EPI; 2) increased albumin/creatinine ratio (ACR ≥30mg/g); and 3) chronic kidney disease (CKD). Arterial stiffness was ascertained by the carotid-femoral pulse wave velocity (PWV). The covariates were sex, age, race/color, level of schooling, smoking, body mass index, total cholesterol/HDL-c glycated hemoglobin, diabetes, systolic blood pressure, heart rate and use of antihypertensive drugs. Logistic regression was used to examine the associations. Results: After all adjustments, 1 m/s increase in PWV was associated with ORs equal to 1.10 (95%CI: 1.04–1.16), 1.10 (95%CI: 1.05–1.16) and 1.12 (95%CI: 1.08–1.17) of low eGFR, high ACR, and CKD, respectively. In subjects without hypertension and diabetes, these ORs were 1.19 (95%CI: 1.07–1.33), 1.20 (95%CI: 1.07–1.32) and 1.21 (95%CI: 1.11–1.30), respectively. Conclusion: The increase in PWV was associated with all renal dysfunction markers, even in individuals without hypertension and diabetes, suggesting a relation that is not completely mediated by the presence of these conditions. [ABSTRACT FROM AUTHOR]

Plasmodium vivax remains an important cause of malaria in South America and the Asia-Pacific. Naturally acquired antibody responses against multiple P. vivax proteins have been described in numerous countries, however, direct comparison of these responses has been difficult with different methodologies employed. We measured antibody responses against 307 P. vivax proteins at the time of P. vivax infection, and at 2–3 later time-points in three countries. We observed that seropositivity rates at the time of infection were highest in Thailand, followed by Brazil then PNG, reflecting the level of antigenic input. The majority of sero-reactive antigens in all sites induced short-lived antibody responses with estimated half-lives of less than 6 months, although there was a trend towards longer-lived responses in PNG children. Despite these differences, IgG seropositivity rates, magnitude and longevity were highly and significantly rank-correlated between the different regions, suggesting such features are reflective of the individual protein. [ABSTRACT FROM AUTHOR]

Background: Plasmodium vivax malaria (Pv-malaria) is still considered a neglected disease despite an alarming number of individuals being infected annually. Malaria pathogenesis occurs with the onset of the vector-parasite-host interaction through the binding of pathogen-associated molecular patterns (PAMPs) and receptors of innate immunity, such as toll-like receptors (TLRs). The triggering of the signaling cascade produces an elevated inflammatory response. Genetic polymorphisms in TLRs are involved in susceptibility or resistance to infection, and the identification of genes involved with Pv-malaria response is important to elucidate the pathogenesis of the disease and may contribute to the formulation of control and elimination tools. Methodology/Principal findings: A retrospective case-control study was conducted in an intense transmission area of Pv-malaria in the state of Amazonas, Brazil. Genetic polymorphisms (SNPs) in different TLRs, TIRAP, and CD14 were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis in 325 patients infected with P. vivax and 274 healthy individuals without malaria history in the prior 12 months from the same endemic area. Parasite load was determined by qPCR. Simple and multiple logistic/linear regressions were performed to investigate association between the polymorphisms and the occurrence of Pv-malaria and parasitemia. The C/T (TLR5 R392StopCodon) and T/T (TLR9 -1486C/T) genotypes appear to be risk factors for infection by P. vivax (TLR5: C/C vs. C/T [OR: 2.116, 95% CI: 1.054–4.452, p = 0.031]; TLR9: C/C vs. T/T [OR: 1.919, 95% CI: 1.159–3.177, p = 0.010]; respectively). Fever (COEF = 7599.46, 95% CI = 3063.80–12135.12, p = 0.001) and the C/C genotype of TLR9 -1237C/T (COEF = 17006.63, 95% CI = 3472.83–30540.44, p = 0.014) were independently associated with increased parasitemia in patients with Pv-malaria. Conclusions: Variants of TLRs may predispose individuals to infection by P. vivax. The TLR5 R392StopCodon and TLR9 -1486C/T variants are associated with susceptibility to Pv-malaria. Furthermore, the TLR9 variant -1237C/C correlates with high parasitemia. [ABSTRACT FROM AUTHOR]

Background: Leishmaniasis is one of the most important zoonotic diseases spread in Latin America. Since many species are involved in dog infection with different clinical manifestations, the development of specific diagnostic tests is mandatory for more accurate disease control and vaccine strategies. Methodology/Principal findings: Seventy-five 15-mer peptides covering the sequence of recombinant Leishmania donovani virulence factor A2 (recLdVFA2) protein were prepared by Spot synthesis. Membrane-bound peptides immunoreactivity with sera from dogs immunized with recLdVFA2 and with a specific anti-recLdVFA2 monoclonal antibody allowed mapping of continuous B-cell epitopes. Five epitopes corresponding to the N-terminal region of recLdVFA2 (MKIRSVRPLVVLLVC, RSVRPLVVLLVCVAA, RPLVVLLVCVAAVLA, VVLLVCVAAVLALSA and LVCVAAVLALSASAE, region 1–28) and one located within the repetitive units (PLSVGPQAVGLSVG, regions 67–81 and 122–135) were identified. A 34-mer recLdVFA2-derived bi-epitope containing the sequence MKIRSVRPLVVLLVC linked to PLSVGPQAVGLSVG by a Gly-Gly spacer was chemically synthesized in its soluble form. The synthetic bi-epitope was used as antigen to coat ELISA plates and assayed with dog sera for in vitro diagnosis of canine visceral leishmaniasis (CVL). The assay proved to be highly sensitive (100%) and specific (100%). Conclusions/Significance: Our work suggests that synthetic peptide-based ELISA strategy may be useful for the development of a sensitive and highly specific serodiagnosis for CVL or other parasitic diseases. [ABSTRACT FROM AUTHOR]

Peanut (Arachis hypogaea L.) is the fourth most consumed oleaginous plant in the world, producing seeds with high contents of lipids, proteins, vitamins, and carbohydrates. Biological activities of different extracts of this species have already been evaluated by many researchers, including antioxidant, antitumoral, and antibacterial. In this work, the allelopathic activity of extracts from different Brazilian peanut cultivars against lettuce (Lactuca sativa) and two weed plants (Commelina benghalensis and Ipomoea nil) was studied. Aerial parts, roots, seeds, and seed coats were used for the preparation of crude extracts. Seed extract partitioning was performed with n-hexane, dichloromethane, ethyl acetate, n-butanol, and aqueous residue. Germination and growth of hypocotyls and rootlets were evaluated after one and five days of incubation with plant extracts, respectively. Crude seed extract and its dichloromethanic partition displayed highest allelopathic activity. These results contribute for the study of new potential natural herbicides. [ABSTRACT FROM AUTHOR]

As a common problem in long-term care facilities (LTCFs), anemia affects 25–63% of the elderly. The aim of the present study was to describe the prevalence and characteristics of anemia and its associated factors in the institutionalized elderly. The cross-sectional study was carried out with three hundred thirteen individuals aged ≥ 60 years, of both genders, living in long-term care facilities for the elderly in Salvador, Bahia, Brazil. Poisson regression (PR) with robust variance estimates was used to assess the factors related to anemia. The prevalence of anemia was 38%. Mild anemia was predominant in both genders (male: 26.8%; female: 21.1%), as normocytic and normochromic anemia, with no anisocytosis (69.75%). Anemia was associated with thinness (PR: 1.68; 95% CI: 1.04–2.72) and with moderate (PR: 1.98; 95% CI: 1.07–3.63) and total (PR: 2.61; 95% CI: 1.34–5.07) dependence in the final model. Severe dependence exhibited borderline significance (PR: 1.94; 95% CI: 1.00–3.77). The prevalence of anemia was high in the institutionalized elderly in both genders, with characteristics suggesting chronic diseases as the causal factor, and the frequency of occurrence was higher in thinness elderly with moderate to total dependence. [ABSTRACT FROM AUTHOR]

Candida albicans caused 44% of the overall candidemia episodes from 2006 to 2010 in our university tertiary care hospital. As different antifungal agents are used in therapy and also immunocompromised patients receive fluconazole prophylaxis in our institution, this study aimed to perform an antifungal susceptibility surveillance with the C.albicans bloodstream isolates and to characterize the fluconazole resistance in 2 non-blood C.albicans isolates by sequencing ERG11 gene. The study included 147 C. albicans bloodstream samples and 2 fluconazole resistant isolates: one from oral cavity (LIF 12560 fluconazole MIC: 8μg/mL) and one from esophageal cavity (LIF-E10 fluconazole MIC: 64μg/mL) of two different patients previously treated with oral fluconazole. The in vitro antifungal susceptibility to amphotericin B (AMB), 5-flucytosine (5FC), fluconazole (FLC), itraconazole (ITC), voriconazole (VRC), caspofungin (CASP) was performed by broth microdilution methodology recommended by the Clinical and Laboratory Standards Institute documents (M27-A3 and M27-S4, CLSI). All blood isolates were classified as susceptible according to CLSI guidelines for all evaluated antifungal agents (MIC range: 0,125–1.00 μg/mL for AMB, ≤0.125–1.00 μg/mL for 5FC, ≤0.125–0.5 μg/mL for FLC, ≤0.015–0.125 μg/mL for ITC, ≤0.015–0.06 μg/mL for VRC and ≤0.015–0.125 μg/mL for CASP). In this study, we also amplified and sequenced the ERG11 gene of LIF 12560 and LIF-E10 C.albicans isolates. Six mutations encoding distinct amino acid substitutions were found (E116D, T128K, E266D, A298V, G448V and G464S) and these mutations were previously described as associated with fluconazole resistance. Despite the large consumption of antifungals in our institution, resistant blood isolates were not found over the trial period. Further studies should be conducted, but it may be that the very prolonged direct contact with the oral antifungal agent administered to the patient from which was isolated LIF E-10, may have contributed to the development of resistance. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate physiological characteristics and oil and protein content in four soybean (Glycine max (L.) Merr.) cultivars (BRS 133, BRS 206, BRS 239 and CD 202) which were harvested in four different periods (R7 stage, 7, 14 and 21 days after the first harvest stage) and produced over the growing season 2004-2005 in two sites of the Mato Grosso do Sul State, Brazil, Sidrol~ndia (21°00' Slat, 55°01' W long), and Dourados (22°11' Slat, 54°55' W long). A randomized complete block design was used in a split-plot experiment with three replicates. Seeds were evaluated by means of a germination test, accelerated aging and seedling emergence on sand. Oil content and protein in seed and soybean meal were also analyzed. BRS 133 and BRS 206 cultivars showed higher values of seed-protein, 35.67 and 35.0%, respectively, which also evidenced higher soybean meal protein content, 43.04 and 46.83%, respectively. The highest oil content was found in cv. CD 202, with a mean value of 22.63%. Germination and seed vigor potentials were significantly affected by harvest periods, which presented a significant reduction when soybean harvest was delayed, such characteristics could affect the plant potential for fast growth and adequate develop of soybean plants. [ABSTRACT FROM AUTHOR]