Risk factors for dengue virus infection in rural Amazonia: Population-based cross-sectional surveys

A comparison of dengue virus (DENV) antibody levels in paired serum samples collected from predominantly DENV-naive residents in an agricultural settlement in Brazilian Amazonia (baseline seroprevalence, 18.3%) showed a seroconversion rate of 3.67 episodes/100 person-years at risk during 12 months of follow-up. Multivariate analysis identified male sex, poverty, and migration from extra-Amazonian states as significant predictors of baseline DENY seropositivity, whereas male sex, a history of clinical diagnosis of dengue fever, and travel to an urban area predicted subsequent seroconversion. The laboratory surveillance of acute febrile illnesses implemented at the study site and in a nearby town between 2004 and 2006 confirmed 11. DENV infections among 102 episodes studied with DENV IgM detection, reverse transcriptase-polymerise chain reaction, and virus isolation; DENV-3 was isolated. Because DENV exposure is associated with migration or travel, personal protection measures when visiting high-risk urban areas may reduce the incidence of DENV infection in this rural population.

Toll-Like Receptor 4 Signaling Leads to Severe Fungal Infection Associated with Enhanced Proinflammatory Immunity and Impaired Expansion of Regulatory T Cells

Toll-like receptors (TLRs) present in innate immune cells recognize pathogen molecular patterns and influence immunity to control the host-parasite interaction. The objective of this study was to characterize the involvement of TLR4 in the innate and adaptive immunity to Paracoccidioides brasiliensis, the most important primary fungal pathogen of Latin America. We compared the responses of C3H/HeJ mice, which are naturally defective in TLR4 signaling, with those of C3H/HePas mice, which express functional receptors, after in vitro and in vivo infection with P. brasiliensis. Unexpectedly, we verified that TLR4-defective macrophages infected in vitro with P. brasiliensis presented decreased fungal loads associated with impaired synthesis of nitric oxide, interleukin-12 (IL-12), and macrophage chemotactic protein 1 (MCP-1). After intratracheal infection with 1 million yeasts, TLR4-defective mice developed reduced fungal burdens and decreased levels of pulmonary nitric oxide, proinflammatory cytokines, and antibodies. TLR4-competent mice produced elevated levels of IL-12 and tumor necrosis factor alpha (TNF-alpha), besides cytokines of the Th17 pattern, indicating a proinflammatory role for TLR4 signaling. The more severe infection of TLR4-normal mice resulted in increased influx of activated macrophages and T cells to the lungs and progressive control of fungal burdens but impaired expansion of regulatory T cells (Treg cells). In contrast, TLR4-defective mice were not able to clear their diminished fungal burdens totally, a defect associated with deficient activation of T-cell immunity and enhanced development of Treg cells. These divergent patterns of immunity, however, resulted in equivalent mortality rates, indicating that control of elevated fungal growth mediated by vigorous inflammatory reactions is as deleterious to the hosts as low fungal loads inefficiently controlled by limited inflammatory reactions.

Seroprevalence of orthopoxvirus in an Amazonian rural village, Acre, Brazil

Vaccinia virus strains from the family Poxviridae have been frequently isolated in Brazil and associated with outbreaks of exanthematic disease affecting cows and humans. An ELISA IgG was applied to evaluate the seroprevalence of orthopoxviruses in a community located in a rural settlement in the Amazon region, where no orthopoxvirus outbreaks have yet been reported. An overall seroprevalence of 27.89% was found, and it was 23.38% in the non-vaccinated population (smallpox vaccination). These results strongly suggest that orthopoxviruses circulate in this population, and it is the first finding of seropositivity for orthopoxviruses in a population without any previously reported outbreaks.

Population-Based Multicentric Survey of Hepatitis B Infection and Risk Factor Differences among Three Regions in Brazil

This multicentric population-based study in Brazil is the first national effort to estimate the prevalence of hepatitis B (HBV) and risk factors in the capital cities of the Northeast. Central-West, and Federal Districts (2004-2005). Random multistage cluster sampling was used to select persons 13-69 years of age. Markers for HBV were tested by enzyme-linked immunosorbent assay. The HBV genotypes were determined by sequencing hepatitis B surface antigen (HBsAg). Multivariate analyses and simple catalytic model were performed. Overall. 7,881 persons were inculded < 70% were not vaccinated. Positivity for HBsAg was less than 1% among non-vaccinated persons and genotypes A, D, and F co-circulated. The incidence of infection increased with age with similar force of infection in all regions. Males and persons having initiated sexual activity were associated with HBV infection in the two settings: healthcare jobs and prior hospitalization were risk factors in the Federal District. Our survey classified these regions as areas with HBV endemicity and highlighted the risk factors differences among the settings.

Association of Human T Lymphotropic Virus 1 Amplification of Periodontitis Severity with Altered Cytokine Expression in Response to a Standard Periodontopathogen Infection

Background. Periodontal diseases (PDs) are infectious diseases in which periodontopathogens trigger chronic inflammatory and immune responses that lead to tissue destruction. Recently, viruses have been implicated in the pathogenesis of PDs. Individuals infected with human T lymphotropic virus 1 (HTLV-1) present with abnormal oral health and a marked increased prevalence of periodontal disease. Methods. In this study, we investigated the patterns of periodontopathogen infection and local inflammatory immune markers in HTLV-1-seropositive individuals with chronic periodontitis (CP/HTLV-1 group) compared with HTLV-1 -seronegative individuals with chronic periodontitis (CP group) and periodontally healthy, HTLV-1 -seronegative individuals (control group). Results. Patients in the CP/HTLV-1 group had significantly higher values of bleeding on probing, mean probing depth, and attachment loss than patients in the CP group. The expression of tumor necrosis factor a and interleukin (IL) 4 was found to be similar in the CP and CP/HTLV-1 groups, whereas IL-12 and IL-17 levels trended toward a higher expression in the CP/HTLV-1 group. A significant increase was seen in the levels of IL-1 beta and interferon gamma in the CP/HTLV-1 group compared with the CP group, whereas expression of the regulatory T cell marker FOXp3 and IL-10 was significantly decreased in the lesions from the CP/HTLV-1 group. Interestingly, similar frequency and/or load of periodontopathogens (Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, and Aggregatibacter actinomycetemcomitans) and frequency of viruses (herpes simplex virus 1, human cytomegalovirus, and Epstein-Barr virus) characteristically associated with PDs were found in the CP/HTLV and CP groups. Conclusions. HTLV-1 may play a critical role in the pathogenesis of periodontal disease through the deregulation of the local cytokine network, resulting in an exacerbated response against a standard periodontopathogen infection.

Prevalence of hepatitis B and C serological markers among first-time blood donors in Brazil: A multi-center serosurvey

Little data are available on the seroprevalence of, and risk factors for hepatitis B and C viruses (HBV and HCV) infection in Latin American countries. A multi-center serosurvey was conducted among 3,598 first-time blood donors (65% men) from Sao Paulo, Salvador and Manaus in Brazil. The gender-specific seroprevalences of antibodies against hepatitis B core antigen (anti-HBc) and of the hepatitis B surface antigen (HBsAg) in anti-HBc-positive sera were measured, and risk factors analyzed by gender. The gender-specific seroprevalences of antibodies against HCV (anti-HCV) were measured, but risk factors for HCV were not determined. Anti-HBc and HBsAg seroprevalences were not significantly different in men [101/2,341 (4.31%) and 4/2,229 (0.18%), respectively] and women [65/1,237 (5.25%) and 8/ 1,169 (0.68%), respectively], whereas the seroprevalence of anti-HCV was higher in women (12/1,238 [0.97%] vs. 9/2,353 [0.38%]; odds ratio [OR] = 2.49; 95% confidence interval [Cl]: 1.0-6.0). No significant difference for HBV infection was found across the three study sites or by ethnic group. The seroprevalence of anti-HBc increased with age, but decreased with education level in both genders. Lifetime number of sexual partners was associated with anti-HBc prevalence among men (OR = 1.95; 95% Cl: 1.2-3.1), but not women. The seroprevalence of HBV and HCV was low among Brazilian blood donors, and exposure increased with age in both genders.

Evolutionary history of Dengue virus type 4: Insights into genotype phylodynamics

Dengue virus type 4 (DENV-4) circulates in tropical and subtropical countries from Asia and the Americas. Despite the importance of dengue virus distribution, little is known about the worldwide viral spread. Following a Bayesian phylogenetic approach we inferred the evolutionary history of 310 isolates sampled from 37 countries during the time period 1956-2008 and the spreading dynamics for genotypes I and II. The region (tropical rainforest biome) comprised by Malaysia-Thailand was the most likely ancestral area from which the serotype has originated and spread. Interestingly, cross-correlation analysis on demographic time series with the Asian sequences showed a statistically significant negative correlation that could be suggestive of competition among genotypes within the same serotype. (C) 2011 Elsevier B.V. All rights reserved.

Paracoccidioidomycosis-related mortality trend, state of Sao Paulo, Brazil: a study using multiple causes of death

Objective. To investigate mortality in which paracoccidioidomycosis appears on any line or part of the death certificate. Method. Mortality data for 1985-2005 were obtained from the multiple cause-of-death database maintained by the Sao Paulo State Data Analysis System (SEADE). Standardized mortality coefficients were calculated for paracoccidioidomycosis as the underlying cause-of-death and as an associated cause-of-death, as well as for the total number of times paracoccidioidomycosis was mentioned on the death certificates. Results. During this 21-year period, there were 1950 deaths related to paracoccidioidomycosis; the disease was the underlying cause-of-death in 1 164 cases (59.69%) and an associated cause-of-death in 786 (40.31%). Between 1985 and 2005 records show a 59.8% decline in the mortality coefficient due to paracoccidioidomycosis as the underlying cause and a 53.0% decline in the mortality as associated cause. The largest number of deaths occurred among men, in the older age groups, and among rural workers, with an upward trend in winter months. The main causes associated with paracoccidioidomycosis as the underlying cause-of-death were pulmonary fibrosis, chronic lower respiratory tract diseases, and pneumonias. Malignant neoplasms and AIDS were the main underlying causes when paracoccidioidomycosis was an associated cause-of-death. The decision tables had to be adapted for the automated processing of causes of death in death certificates where paracoccidioidomycosis was mentioned. Conclusions. Using the multiple cause-of-death method together with the traditional underlying cause-of-death approach provides a new angle on research aimed at broadening our understanding of the natural history of paracoccidioidomycosis.

Relation of pretreatment sequence diversity in NS5A region of HCV genotype 1 with immune response between pegylated-INF/ribavirin therapy outcomes

Hepatitis C virus (HCV) infection frequently persists despite substantial virus-specific immune responses and the combination of pegylated interferon (INF)-alpha and ribavirin therapy. Major histocompatibility complex class I restricted CD8+ T cells are responsible for the control of viraemia in HCV infection, and several studies suggest protection against viral infection associated with specific HLAs. The reason for low rates of sustained viral response (SVR) in HCV patients remains unknown. Escape mutations in response to cytotoxic T lymphocyte are widely described; however, its influence in the treatment outcome is ill understood. Here, we investigate the differences in CD8 epitopes frequencies from the Los Alamos database between groups of patients that showed distinct response to pegylated alpha-INF with ribavirin therapy and test evidence of natural selection on the virus in those who failed treatment, using five maximum likelihood evolutionary models from PAML package. The group of sustained virological responders showed three epitopes with frequencies higher than Non-responders group, all had statistical support, and we observed evidence of selection pressure in the last group. No escape mutation was observed. Interestingly, the epitope VLSDFKTWL was 100% conserved in SVR group. These results suggest that the response to treatment can be explained by the increase in immune pressure, induced by interferon therapy, and the presence of those epitopes may represent an important factor in determining the outcome of therapy.

Expression Patterns of Cell Adhesion Molecules in Mice`s Lung After Administration of Meso-2,3-Dimercaptosuccinic Acid-Coated Maghemite Nanoparticles

We studied the expression pattern of cell adhesion molecules associated to transendothelial migration of leukocytes in different lung`s vascular compartments after administration of a magnetic fluid sample containing maghemite nanoparticles surface-coated with meso-2,3-dimercaptosuccinic acid. The analyses were conducted in mice 4 and 12 h after endovenous administration of the magnetic fluid in control mice. Firstly, the migratory activity of leukocytes after magnetic fluid surface-coated with meso-2,3-dimercaptosuccinic acid administration was confirmed using broncho-alveolar lavage and light microscopy. Then, the expression of cell adhesion molecules in the lung`s vascular compartments was investigated by immunofluorescence microscopy of frozen sections, using antibodies against L-selectin, P-selectin, E-selectin, macrophage antigen-1, and leukocyte function associated antigen-1. L- and P-selectin showed similar pattern of expression in the pulmonary vasculature in animals treated with magnetic fluid and in the control group. In contrast, macrophage antigen-1 and leukocyte function associated antigen-1 were found in capillary only in animals treated with magnetic fluid surface-coated with meso-2,3-dimercaptosuccinic acid administration. In addition, after magnetic fluid administration E-selectin was found in post-capillary sites. Our findings demonstrated that magnetic fluid surface-coated with meso-2,3-dimercaptosuccinic acid administration exhibits modulation effects on expression patterns of E-selectin, macrophage antigen-1, and leukocyte function associated antigen-1 in the lung`s vascular compartments. These findings are very important in a strategy to reduce the potential toxicity of magnetic fluid surface-coated with meso-2,3-dimercaptosuccinic acid administration for medical applications.

Expression of a dendritic cell maturation marker CD83 on tumor cells from lung cancer patients and several human tumor cell lines: is there a biological meaning behind it?

The present paper shows, for the first time, the membrane expression of the dendritic cell maturation marker CD83 on tumor cells from lung cancer patients. CD83 was also detected on freshly cultured fibroblast-like cells from these tissues and on several adherent human tumor cell lines (lung adenocarcinomas P9, A459 and A549, melanomas A375 and C81-61, breast adenocarcinomas SKBR-3 and MCF-7 and colon carcinoma AR42-J), but not in the non-adherent MOT leukemia cell line. CD83 may have immunosuppressive properties and its expression by cancer cells could have a role in facilitating tumor growth.

A DNA Vaccine Encoding the Enterohemorragic Escherichia coli Shiga-Like Toxin 2 A(2) and B Subunits Confers Protective Immunity to Shiga Toxin Challenge in the Murine Model

Production of verocytotoxin or Shiga-like toxin (Stx), particularly Stx2, is the basis of hemolytic uremic syndrome, a frequently lethal outcome for subjects infected with Stx2-producing enterohemorrhagic Escherichia coli (EHEC) strains. The toxin is formed by a single A subunit, which promotes protein synthesis inhibition in eukaryotic cells, and five B subunits, which bind to globotriaosylceramide at the surface of host cells. Host enzymes cleave the A subunit into the A(1) peptide, endowed with N-glycosidase activity to the 28S rRNA, and the A(2) peptide, which confers stability to the B pentamer. We report the construction of a DNA vaccine (pStx2 Delta AB) that expresses a nontoxic Stx2 mutated form consisting of the last 32 amino acids of the A(2) sequence and the complete B subunit as two nonfused polypeptides. Immunization trials carried out with the DNA vaccine in BALB/c mice, alone or in combination with another DNA vaccine encoding granulocyte-macrophage colony-stimulating factor, resulted in systemic Stx-specific antibody responses targeting both A and B subunits of the native Stx2. Moreover, anti-Stx2 antibodies raised in mice immunized with pStx2 Delta AB showed toxin neutralization activity in vitro and, more importantly, conferred partial protection to Stx2 challenge in vivo. The present vector represents the second DNA vaccine so far reported to induce protective immunity to Stx2 and may contribute, either alone or in combination with other procedures, to the development of prophylactic or therapeutic interventions aiming to ameliorate EHEC infection-associated sequelae.

Severe novel influenza A (H1N1) infection in cancer patients

Patients and methods: Clinical data from all patients admitted with acute respiratory failure due to novel viral H1N1 infection were reviewed. Lung tissue was submitted for viral and bacteriological analyses by real-time RT-PCR, and autopsy was conducted on all patients who died. Results: Eight patients were admitted, with ages ranging from 55 to 65 years old. There were five patients with solid organ tumors (62.5%) and three with hematological malignancies (37.5%). Five patients required mechanical ventilation and all died. Four patients had bacterial bronchopneumonia. All deaths occurred due to multiple organ failure. A milder form of lung disease was present in the three cases who survived. Lung tissue analysis was performed in all patients and showed diffuse alveolar damage in most patients. Other lung findings were necrotizing bronchiolitis or extensive hemorrhage. Conclusions: H1N1 viral infection in patients with cancer can cause severe illness, resulting in acute respiratory distress syndrome and death. More data are needed to identify predictors of unfavorable evolution in these patients.

Immunomodulatory effects of Pteridium aquilinum on natural killer cell activity and select aspects of the cellular immune response of mice

Pteridium aquilinum (bracken fern) is one of the most common plants. Epidemiological studies have revealed a higher risk of certain types of cancers (i.e., esophageal, gastric) in people who consume bracken fern directly ( as crosiers or rhizomes) or indirectly through the consumption of milk from livestock that fed on the plant. In animals, evidence exists regarding the associations between chronic bracken fern intoxication, papilloma virus infection, and the development of carcinomas. While it is possible that some carcinogens in bracken fern could be responsible for these cancers in both humans and animals, it is equally plausible that the observed increases in cancers could be related to induction of an overall immunosuppression by the plant/its various constituents. Under the latter scenario, normal tumor surveillance responses against nascent (non-bracken-induced) cancers or responses against viral infections ( specifically those linked to induction of cancers) might be adversely impacted by continuous dietary exposure to this plant. Therefore, the overall objective of this study was to evaluate the immunomodulatory effects of bracken fern following daily ingestion of its extract by a murine host over a period of 14 ( or up to 30) days. In C57BL/6 mice administered ( by gavage) the extract, histological analyses revealed a significant reduction in splenic white pulp area. Among a variety of immune response parameters/functions assessed in these hosts and isolated cells, both delayed-type hypersensitivity (DTH) analysis and evaluation of IFN gamma. production by NK cells during T(H)1 priming were also reduced. Lastly, the innate response in these hosts-assessed by analysis of NK cell cytotoxic functionality-was also diminished. The results here clearly showed the immunosuppressive effects of P. aquilinum and that many of the functions that were modulated could contribute to the increased risk of cancer formation in exposed hosts.

Cathepsin X cleaves the beta 2 cytoplasmic tail of LFA-1 inducing the intermediate affinity form of LFA-1 and alpha-actinin-1 binding

The motility of T cells depends on the dynamic spatial regulation of integrin-mediated adhesion and de-adhesion. Cathepsin X, a cysteine protease, has been shown to regulate T-cell migration by interaction with lymphocyte function associated antigen-1 (LFA-1). LFA-1 adhesion to the ICAM-1 is controlled by the association of actin-binding proteins with the cytoplasmic tail of the beta(2) chain of LFA-1. Cleavage by cathepsin X of the amino acid residues S(769), E(768) and A(767) from the C-terminal of the beta(2) cytoplasmic tail of LFA-1 is shown to promote binding of the actin-binding protein alpha-actinin-1. Furthermore, cathepsin X overexpression reduced LFA-1 clustering and induced an intermediate affinity LFA-1 conformation that is known to associate with a-actinin-1. increased levels of intermediate affinity LFA-1 resulted in augmented cell spreading due to reduced attachment of T cells to the ICAM-1-coated surface. Gradual cleavage of LFA-1 by cathepsin X enables the transition between intermediate and high affinity LFA-1, an event that is crucial for effective T-cell migration.