Dietary ß-glucan (MacroGard®) improves innate immune responses and disease resistance in Nile tilapia regardless of the administration period.

The effects of dietary ß-glucan on innate immune responses have been shown in a number of different vertebrate species. However, there is conflicting information about the period of administration (shorter vs. longer), and it is also unclear to what extent ß-glucan's effects can be observed post-treatment in fish. Thus, we fed Nile tilapia for 0 (control group; 45 days of control diet), 15 (30 days of control followed by 15 days of ß-glucan), 30 (15 days of control followed by 30 days of ß-glucan) or 45 days with a diet containing 0.1% of ß-glucan (MacroGard®). We evaluated the growth performance at the end of the ß-glucan feeding trial and the innate immune function immediately after the feeding trial and 7 and 14 days post-feeding trial. In addition, at day 10 post-feeding trial, we assessed the tilapia's resistance against a bacterial infection. No significant differences were observed in growth performance between the groups; however, fish fed with ß-glucan for 30 and 45 days had higher (approx. 8%) relative weight gain compared to the control. Regardless of the administration period, fish fed with ß-glucan had higher innate immune responses immediately after the feeding trial such as lysozyme activity in plasma, liver and intestine and respiratory burst compared to the control, and in general these differences were gradually reduced over the withdrawal period (up to 14 days). No differences were observed in the plasma hemolytic activity of the complement or myeloperoxidase activity in plasma or intestine. Moreover, fish from the control group had early mortalities (2 vs. 4-5 days post-infection, respectively) and a lower survival rate (60 vs. 80%, respectively) compared to fish fed with ß-glucan for 15 or 30 days, and, interestingly, fish fed for 45 days with ß-glucan had no mortality. This study indicates that regardless of the administration period (i.e., 15 up to 45 days), the ß-glucan improved the innate immune responses and the tilapia's resistance to disease, and this protection could be observed up to 10 days post-feeding trial, adding in vivo evidence that ß-glucan may contribute to a trained innate immunity. Additionally, we showed that a longer period of administration did not cause immunosuppression as previously hypothesized but promoted further growth and immune performance. These findings are relevant to the aquaculture industry and demonstrate that a longer ß-glucan feeding protocol may be considered to achieve better results.

Analyzing the reach of public health campaigns based on multidimensional aspects: the case of the syphilis epidemic in Brazil.

BACKGROUND: Public health campaigns aim to promote awareness, increase knowledge, and encourage a target population to adopt desirable attitudes and behaviors. Assessing their reach from a multidimensional perspective through information technology can facilitate the development of more effective campaigns in public health response. METHODS: We scrutinized seven data sources from different perspectives to assess a health campaign launched in Brazil named "Syphilis No!". This campaign is part of an Agenda for strategic actions to reduce syphilis in Brazil which includes dissemination of educommunication materials to remind people of the importance of syphilis prevention, emphasizing "test, treat and cure" concept. We developed a multidimensional analysis framework and implemented an information system to process the data from a time series perspective, and assessed the effects over time, both before and after the campaign. We descriptively analyzed data related to the campaign, including e-news, search engine activity, online courses, serological tests, medication distribution and case notification rates. FINDINGS: Regarding search engine activity, we observed the highest volume of search during the first week of campaigns in 2018 (between November 25th and December 7th). Nevertheless, analyzing this data in a trend plot revealed sustained growth until the end of 2019. From March 2018, the amount of e-news posts related to syphilis in Brazil, indexed by Google, followed an increasing slope, with a record peak in October 2019. In addition, data showed that 12 new online courses related to syphilis disease were available on the AVASUS Platform Learning Management System (LMS), to support efforts to promote lifelong learning for health professionals, teachers, and students. These courses reached more than 22,000 students between February 2019 and September 2020. Serological test data showed that the number of tests carried out in 2019 were 375·18% more than in 2015, even accounting for population growth. Finally, starting from the middle of 2018, the syphilis case notification rates followed a decreasing curve. INTERPRETATION: From this perspective, the "Syphilis No!" Project was a positive influence, inducing policy to fight syphilis in Brazil by supporting the implementation of a testing, treatment, and cure agenda (#TesteTrateCure). Certainly, this inference was made by analyzing multidimensional aspects and because, prior to 2018, the country had largely neglected this disease, with no records of communication actions during that period.

Development of Fish Immunity and the Role of ß-Glucan in Immune Responses.

Administration of ß-glucans through various routes, including immersion, dietary inclusion, or injection, have been found to stimulate various facets of immune responses, such as resistance to infections and resistance to environmental stress. ß-Glucans used as an immunomodulatory food supplement have been found beneficial in eliciting immunity in commercial aquaculture. Despite extensive research involving more than 3000 published studies, knowledge of the receptors involved in recognition of ß-glucans, their downstream signaling, and overall mechanisms of action is still lacking. The aim of this review is to summarize and discuss what is currently known about of the use of ß-glucans in fish.

Different ß-glucans improve the growth performance and bacterial resistance in Nile tilapia.

The role of glucan as a biologically active immunomodulator has been well documented for more than 40 years. However, the wide diversity of ß-glucan forms and the extraction process has implications for the benefits of these compounds. Biorigin developed two samples of ß-glucans using different biotechnological processes. Thus, in the present study, we fed Nile tilapia (Oreochromis niloticus) diets containing these two ß-glucan molecules (BG01 and BG02) for 30 days prior to bacterial infection with Streptococcus agalactiae. The results showed that the different ß-glucan samples exhibited biologically differently behaviors, but both increased the resistance against bacterial infection. Specifically, BG01 increased immunostimulation, while BG02 improved growth performance. In summary, these findings confirm the benefits of ß-glucans in aquaculture and also provide further evidence of the growth promotion of these compounds.

Detection of dengue NS1 and NS3 proteins in placenta and umbilical cord in fetal and maternal death.

In Brazil, dengue is a public health problem with the occurrence of explosive epidemics. This study reports maternal and fetal deaths due to dengue and which tissues of placenta and umbilical cord were analyzed by molecular methods and immunohistochemistry. The dengue NS3 and NS1 detection revealed the viral presence in different cells from placenta and umbilical cord. In the latter, DENV-2 was detected at a viral titer of 1,02 × 10(4) amounts of viral RNA. It was shown that the DENV markers analyzed here may be an alternative approach for dengue fatal cases investigation, especially involving maternal and fetal death. J. Med. Virol. 88:1448-1452, 2016. © 2016 Wiley Periodicals, Inc.

Liver immunopathogenesis in fatal cases of dengue in children: detection of viral antigen, cytokine profile and inflammatory mediators.

Introduction: Dengue virus (DENV), the etiologic agent of dengue fever illness, represents a global public health concern, mainly in tropical and subtropical areas across the globe. It is well known that this acute viral disease can progress to severe hemorrhagic stages in some individuals, however, the immunopathogenic basis of the development of more severe forms by these patients is yet to be fully understood. Objective: In this context, we investigated and characterized the histopathological features as well as the cytokine profile and cell subpopulations present in liver tissues from three fatal cases of DENV in children. Methods: Hematoxylin and Eosin, Periodic Acid Schiff and Picro Sirius Red staining were utilized for the histopathological analysis. Immunohistochemistry assay was performed to characterize the inflammatory response and cell expression patterns. Results: Vascular dysfunctions such as hemorrhage, vascular congestion and edema associated with a mononuclear infiltrate were observedin all three cases. Liver tissues exhibited increased presence of CD68+ and TCD8+ cells as well as high expression of MMP-9, TNF-a, RANTES, VEGFR-2 mediators. Viral replication was confirmed by the detection of NS3 protein. Conclusion: Taken together, these results evidenced key factors that may be involved in the development of severe alterations in liver tissues of children in response to DENV infection.

Analyzing a national health surveillance strategy to reduce mother-to-child transmission of syphilis: The case of Brazilian investigation committees.

Objectives: This study aimed to analyze the relevance of investigation committees in eliminating mother-to-child transmission of syphilis in Brazil. Methods: Questionnaires and interviews were conducted with health managers of 25 Brazilian Federative Units and Brazil's Federal District. Data were analyzed using Bardin's content analysis technique and subsequently compared with the global prescriptions for syphilis response of the Pan American Health Organization, World Health Organization, and recent research publications examining the course of syphilis in Brazil, in Brazilian regions, and globally. Results: While the investigation committees drew on the successful experience of those in reducing maternal mortality, which helped the country achieve the Millennium Development Goals, they are not demonstrated to be sufficient for preventing mother-to-child transmission of syphilis. The committees' systematic and bureaucratic agenda has not been efficient in managing avoidable factors for syphilis, nor do they operate in the scope of the integration of surveillance and care actions, as recommended by the health policy. Conclusion: The committees' model needs to be reviewed in the context of Brazil's National Health System. The research process should be rescaled in order to remain a cornerstone for the induction of health policy that integrates surveillance and healthcare across Brazilian Federative Units. The advancement toward an automated case management model becomes relevant for the country to meet global commitments to eliminate congenital syphilis transmission and achieve the goals outlined in the 2030 Agenda.

Study of quercetin-loaded liposomes as potential drug carriers: in vitro evaluation of human complement activation.

Liposomes have been employed as potential drug carriers. However, after their in vivo administration, they can be destabilized by proteins of complement system, contributing to the clearance of vesicles from blood circulation. Antioxidant flavonoids such as quercetin have been reported to be beneficial to human health, but their low water solubility and bioavailability limit their enteric administration. Therefore, the development of appropriate flavonoid-carriers could be of great importance to drug therapy. The aim of the present study was to evaluate the activation of human complement system proteins by liposomes composed of soya phosphatidylcholine (SPC) and cholesterol (CHOL) or cholesteryl ethyl ether (CHOL-OET) loaded with quercetin or not. The consumption of complement, via classical (CP) and alternative (AP) pathways, by different vesicles was evaluated using a hemolytic assay and quantitative determination of iC3b and natural antibodies deposited on empty liposomal surfaces by ELISA. The main results showed that empty liposomes composed of large amounts of CHOL consumed more complement components than the others for both CP and AP. Furthermore, replacement of CHOL with CHOL-OET reduced complement consumption via both CP and AP. Incorporation of quercetin did not change CP and AP consumption. Deposition of iC3b, IgG and IgM in vesicles composed of SPC:CHOL-OET at a molar ratio of 1.5:1 was lower compared to the others. Taken together, these observations suggest that liposomes composed of SPC:CHOL-OET at a molar ratio of 1.5:1 are the most appropriate among the vesicles studied herein to be used as a drug carrier system in further investigations.

Pregnancy outcomes following rubella vaccination: a prospective study in the state of Rio de Janeiro, Brazil, 2001-2002.

BACKGROUND: A rubella mass vaccination campaign targeting 15-29-year-old women was performed in Brazil in 2001-2002. Rubella vaccination was contraindicated during pregnancy. A follow-up protocol was implemented for pregnant women who were vaccinated as well as their newborns. The risks of congenital rubella syndrome (CRS) and congenital rubella infection (CRI) after vaccination were assessed according to the pregnant women's immune status. METHODS: This was a prospective, noncontrolled study of pregnancy outcomes in women vaccinated against rubella in the state of Rio de Janeiro, including clinical and laboratory evaluations. RESULTS: Of 2292 reported pregnant women who were vaccinated, 1636 had known outcomes: there were 1577 newborns (96.4%), 52 miscarriages (3.2%), and 7 stillbirths (0.4%). Gestational age at vaccination was ≤ 5 weeks in 75% of the susceptible, vaccinated pregnant women. Nine newborns were positive for immunoglobulin M; 4 were born to susceptible pregnant women, for a 2.0% CRI rate (95% confidence interval, .5%-4.9%); 4 were born to vaccinated pregnant women with indeterminate or unknown status; and 1 had CRS, with a wild-type virus infection. CONCLUSIONS: The absence of vaccine-related CRS cases further supports recommendations to not interrupt a pregnancy exposed to rubella vaccine virus. Monitoring pregnancy outcomes and CRI with vaccine virus can distinguish between wild-type and vaccine virus infections, especially in situations of viral circulation.

Cytokines and inflammatory mediators: Markers involved in interstitial damage to the pancreas in two dengue fever cases associated with acute pancreatitis.

Dengue viral (DENV) infections can lead to acute pancreatitis and associated tissue damage. This study examined the pancreas from two fatal cases of DENV for histopathological changes as well as for the detection of cytokines, and other inflammatory mediators. Tissue sections were prepared for examination by ultrastructural and histopathological techniques. Sections from the pancreas of non-infected individuals were prepared in parallel as a control. The presence of viral replication in macrophages was detected by co-staining for the proteins NS3 and CD68 by immunofluorescence. Immunohistochemistry was used to detect cells that expressed cytokines and inflammatory mediators to characterize the inflammatory response. Edema, acinar necrosis and fibrosis areas associated with a mononuclear infiltrate were found in infected tissues. The major site of virus replication appeared to be macrophages based on their exclusive presentation of the viral protein NS3. Pancreatic tissues from the infected individuals also displayed increased levels of high mobility group box-1, caspase-3, gelatinase B and tumor necrosis factor alpha compared to controls. The presence of virus replicating macrophages in the pancreas was associated with multiple changes in tissue structure that included elevated levels of cytokines and inflammatory markers that may differentiate acute pancreatitis due to DENV infections from other causes.

Use of Interrupted Time Series Analysis in Understanding the Course of the Congenital Syphilis Epidemic in Brazil.

Background: To fight against the rising incidence of syphilis, the Brazilian Ministry of Health (MoH) launched the "Syphilis No!" Project (SNP), with specific resources funded by a parliamentary amendment. Then, in 2018, a national rapid response started to be implemented on the Brazilian Unified Health System (SUS, Sistema Único de Saúde) in two strategic lines (1) to reinforce SUS's universal actions and (2) to implement specific ones to 100 municipalities chosen by the MoH as priorities for syphilis congenital response. In 2015, such localities represented 6895% of congenital syphilis cases in Brazil. In this context, SNP has implemented actions to strengthen epidemiological surveillance of acquired syphilis and congenital syphilis by instituting an integrated and collaborative response through health services networks and reinforcing interstate relations. Methods: A quasi-experimental study using time series analysis was conducted to assess immediate impacts and changes to the trend in national congenital syphilis before and after the project, from September 2016 to December 2019. Data were assessed considering rates of congenital syphilis per 1,000 live births in all priority municipalities (n=100) covered by the project and in non-priority municipalities (n=5,470) from all five macro-regions of Brazil. Findings: Priority municipalities showed a greater reduction (change in trend) in comparison to non-priority. The linear regression model revealed trend changes after the intervention, with both groups of municipalities showing a drop in the average monthly number of cases per 1,000 live births, with a reduction of -0·21 (CI 95% -0·33 to -0·09; p=0·0011) in priority municipalities and of -0·10 (CI 95% -0.19 to -0.02; p=0·0216) in non-priority municipalities. Interpretation: The study using ITS provides important evidence on the direction, timing, and magnitude of the effects of interventions introduced as part of the SNP on congenital syphilis in Brazil. Our results suggest that the Syphilis No! Project influenced the trends of congenital syphilis in Brazil from 2018, with higher reductions achieved in the priority municipalities. Funding: The research is funded by a grant to the Syphilis No! Project from Brazilian Ministry of Health (Project Number: 54/2017). The funders had no role in study design, analysis, decision to publish, or preparation of the manuscript.

In vitro evaluation of the antioxidant activity of liposomal flavonols by the HRP-H2O2-luminol system.

Considering that antioxidant flavonols have been reported to be beneficial to human health, but that their low water solubility and bioavailability limit their administration through systemic route, the development of suitable flavonol-carriers is of great importance for clinical therapeutics. The aim of this study was to prepare liposomes containing flavonols or not and evaluate their antioxidant activity. Vesicles were obtained by ethanol injection method and characterized in terms of entrapment efficiency, size and zeta potential. Inhibitory activity of liposomal flavonols on reactive oxygen species generation was assessed in vitro using luminol-H(2)O(2)-horseradish peroxidase technique. Antioxidant activity of liposomal flavonols is dependent on concentration and chemical structure of active compound. Quercetin and myricetin are the most active flavonols (IC(50) = 0.6-0.9 µmol/L), followed by kaempferol (IC(50) = 3.0-4.5 µmol/L) and galangin (IC(50) = 4.0-7.0 µmol/L). Our results suggest that antioxidant-loaded liposomes may be promising tools for therapy of diseases where oxidative stress is involved.

Spontaneous Abortion and Chikungunya Infection: Pathological Findings.

Intrauterine transmission of the Chikungunya virus (CHIKV) during early pregnancy has rarely been reported, although vertical transmission has been observed in newborns. Here, we report four cases of spontaneous abortion in women who became infected with CHIKV between the 11th and 17th weeks of pregnancy. Laboratorial confirmation of the infection was conducted by RT-PCR on a urine sample for one case, and the other three were by detection of IgM anti-CHIKV antibodies. Hematoxylin and eosin (H&E) staining and an electron microscopy assay allowed us to find histopathological, such as inflammatory infiltrate in the decidua and chorionic villi, as well as areas of calcification, edema and the deposition of fibrinoid material, and ultrastructural changes, such as mitochondria with fewer cristae and ruptured membranes, endoplasmic reticulum with dilated cisterns, dispersed chromatin in the nuclei and the presence of an apoptotic body in case 1. In addition, by immunohistochemistry (IHC), we found a positivity for the anti-CHIKV antibody in cells of the endometrial glands, decidual cells, syncytiotrophoblasts, cytotrophoblasts, Hofbauer cells and decidual macrophages. Electron microscopy also helped in identifying virus-like particles in the aborted material with a diameter of 40-50 nm, which was consistent with the size of CHIKV particles in the literature. Our findings in this study suggest early maternal fetal transmission, adding more evidence on the role of CHIKV in fetal death.

Selenization of S. cerevisiae increases its protective potential in experimental autoimmune encephalomyelitis by triggering an intestinal immunomodulatory loop.

Multiple sclerosis is an autoimmune disease that affects the myelinated central nervous system (CNS) neurons and triggers physical and cognitive disabilities. Conventional therapy is based on disease-modifying drugs that control disease severity but can also be deleterious. Complementary medicines have been adopted and evidence indicates that yeast supplements can improve symptoms mainly by modulating the immune response. In this investigation, we evaluated the therapeutic potential of Saccharomyces cerevisiae and its selenized derivative (Selemax) in experimental autoimmune encephalomyelitis (EAE). Female C57BL/6 mice submitted to EAE induction were orally supplemented with these yeasts by gavage from day 0 to day 14 after EAE induction. Both supplements determined significant reduction in clinical signs concomitantly with diminished Th1 immune response in CNS, increased proportion of Foxp3+ lymphocytes in inguinal and mesenteric lymph nodes and increased microbiota diversity. However, Selemax was more effective clinically and immunologically; it reduced disease prevalence more sharply, increased the proportion of CD103+ dendritic cells expressing high levels of PD-L1 in mesenteric lymph nodes and reduced the intestinal inflammatory process more strongly than S. cerevisiae. These results suggest a clear gut-brain axis modulation by selenized S. cerevisiae and suggest their inclusion in clinical trials.

Organic Selenium Reaches the Central Nervous System and Downmodulates Local Inflammation: A Complementary Therapy for Multiple Sclerosis?

Multiple sclerosis (MS) is an inflammatory and demyelinating disease of the central nervous system (CNS). The persistent inflammation is being mainly attributed to local oxidative stress and inflammasome activation implicated in the ensuing demyelination and axonal damage. Since new control measures remain necessary, we evaluated the preventive and therapeutic potential of a beta-selenium-lactic acid derivative (LAD-ßSe), which is a source of organic selenium under development, to control experimental autoimmune encephalomyelitis (EAE) that is an animal model for MS. Two EAE murine models: C57BL/6 and SJL/J immunized with myelin oligodendrocyte glycoprotein and proteolipid protein, respectively, and a model of neurodegeneration induced by LPS in male C57BL/6 mice were used. The preventive potential of LAD-ßSe was initially tested in C57BL/6 mice, the chronic MS model, by three different protocols that were started 14 days before or 1 or 7 days after EAE induction and were extended until the acute disease phase. These three procedures were denominated preventive therapy -14 days, 1 day, and 7 days, respectively. LAD-ßSe administration significantly controlled clinical EAE development without triggering overt hepatic and renal dysfunction. In addition of a tolerogenic profile in dendritic cells from the mesenteric lymph nodes, LAD-ßSe also downregulated cell amount, activation status of macrophages and microglia, NLRP3 (NOD-like receptors) inflammasome activation and other pro-inflammatory parameters in the CNS. The high Se levels found in the CNS suggested that the product crossed the blood-brain barrier having a possible local effect. The hypothesis that LAD-ßSe was acting locally was then confirmed by using the LPS-induced neurodegeneration model that also displayed Se accumulation and downmodulation of pro-inflammatory parameters in the CNS. Remarkably, therapy with LAD-ßSe soon after the first remitting episode in SJL/J mice, also significantly downmodulated local inflammation and clinical disease severity. This study indicates that LAD-ßSe, and possibly other derivatives containing Se, are able to reach the CNS and have the potential to be used as preventive and therapeutic measures in distinct clinical forms of MS.

Hepatic damage associated with dengue-2 virus replication in liver cells of BALB/c mice.

One difficulty in studying dengue virus (DENV) is the lack of an experimental model that reproduces the human disease. In a previous work, we have shown that BALB/c mice intraperitoneally inoculated with a DENV-2 isolate presented viremia and mild focal areas of liver injuries. In this study, mice were inoculated by the intravenous route and presented extensive damage areas in the liver tissue, which were evaluated by histopathological and ultrastructural analysis. Hepatic injury was noted mainly around the central vein and portal tracts. Damages consist of hepatocyte injury, including steatosis, swelling and necrosis. Further, erythrophagocytosis, intercellular edema and vascular damages were evident, including hemorrhage, which is characteristic of the dengue-induced hepatitis in human liver. Hepatic lesions were already noted 2 days post infection (p.i.), although effects were more extensive after the seventh day p.i. An increase in alanine aminotransferase and aspartate aminotransferase serum levels was detected 7 and 14 days p.i., respectively, and had correlation to hepatic lesions. Alterations caused by the DENV infection were self-limiting, with a remarkable reduction of all liver damages 49 days p.i. Virus antigens were detected in hepatocytes, Kupffer cells and vascular endothelium, suggesting virus replication in these cells. In situ hybridization, using a probe that anneals in the virus negative RNA strand, showed positive reaction in hepatocytes and vascular endothelium cells of infected mice, thus confirming virus replication in such cells. In general, results revealed that this mouse model reproduces some histopathological effects observed in humans and supports previous findings indicating virus replication in the hepatic tissue.

Effects of the solubility of yeast cell wall preparations on their potential prebiotic properties in dogs.

Derivatives of yeast cell wall (YCW) have been studied for their potential prebiotic effects. Recently, new purified and soluble preparations have been developed in an attempt to increase their biological actions. Two YCW preparations, one conventional and another with higher solubility of the mannan oligosaccharide fraction, were evaluated on dogs. One food formulation was used, divided into the following treatments: CON-control, without yeast cell wall addition; YCW-addition of 0.3% of a conventional yeas cell wall extract; YCWs-addition of 0.3% of a yeast cell wall extract with high mannan oligosaccharide solubility. Twenty-four beagle dogs were used, eight per food, distributed on a block design. Blocks lasted 32 days, and TNF-a, IL-6, IL-10, ex vivo production of hydrogen peroxide and nitric oxide by peripheral neutrophils and monocytes, phagocytic index, and fecal IgA were evaluated at the beginning and end of each period. Additionally, nutrient digestibility, feces production and quality, and fermentation products were quantified. The results were evaluated by analysis of variance and compared using the Tukey test (P<0.05), using the basal immunological parameters as a covariate. The inclusion of YCWs reduced fat digestibility (P<0.05), increased the concentration of butyrate and putrescine, and reduced lactate in feces (P<0.05), showing that mannan oligosaccharide solubilization resulted in higher fermentation of this compound and altered the metabolism of the gut microbiota. Lower IL-6 on serum was verified for dogs fed the YCWs diet (P<0.05), suggesting a reduction in the inflammatory activity of dogs. Higher phagocytic index was verified for peripheral monocytes after the intake of the YCW food, suggesting better innate immunity. In conclusion, the solubilization of the mannooligosaccharide fraction alters its interaction with gut microbiota and biological actions in animals, although both yeast cell wall preparations exhibited prebiotic effects on dogs.

Correction: MOF@activated carbon: a new material for adsorption of aldicarb in biological systems.

Correction for 'MOF@activated carbon: a new material for adsorption of aldicarb in biological systems' by Carlos Alberto Fernandes de Oliveira et al., Chem. Commun., 2013, 49, 6486-6488.

Renal Injury in DENV-4 Fatal Cases: Viremia, Immune Response and Cytokine Profile.

Dengue virus (DENV) infections may result in asymptomatic cases or evolve into a severe disease, which involves multiple organ failure. Renal involvement in dengue can be potentially related to an increased mortality. Aiming to better understand the role of DENV in renal injury observed in human fatal cases, post-mortem investigations were performed in four DENV-4 renal autopsies during dengue epidemics in Brazil. Tissues were submitted to histopathology, immunohistochemistry, viral quantification, and characterization of cytokines and inflammatory mediators. Probably due the high viral load, several lesions were observed in the renal tissue, such as diffuse mononuclear infiltration around the glomerulus in the cortical region and in the medullary vessels, hyalinosis arteriolar, lymphocytic infiltrate, increased capsular fibrosis, proximal convoluted tubule (PCT) damage, edema, PCT debris formation, and thickening of the basal vessel membrane. These changes were associated with DENV-4 infection, as confirmed by the presence of DENV-specific NS3 protein, indicative of viral replication. The exacerbated presence of mononuclear cells at several renal tissue sites culminated in the secretion of proinflammatory cytokines and chemokines. Moreover, it can be suggested that the renal tissue injury observed here may have been due to the combination of both high viral load and exacerbated host immune response.

Antiretroviral therapy-induced paradoxical worsening of previously healed Mycobacterium haemophilum cutaneous lesions in advanced HIV infection.

Mycobacterium haemophilum is a nontuberculous mycobacterium that causes localized or disseminated disease, mainly in immunocompromised hosts. We report the case of a 35-year-old HIV-infected woman who presented with several enlarging cutaneous lesions over the arms and legs. Histopathological examination revealed the diagnosis of a cutaneous mycobacterial disease. Mycobacterial analyses unveiled M. haemophilum infection. Six months after completion of a successful antimycobacterial treatment, she developed an immune reconstitution inflammatory syndrome (IRIS). This paradoxical relapse presented as tenderness, redness and swelling at the precise sites of the healed lesions and took place in the setting of significant recovery of the CD4 cell count (from 05 to 318 cells/mm 3 ). Microbiological analyses of these worsening lesions were negative, and they spontaneously remitted without the initiation of a novel antimycobacterial treatment cycle. M. haemophilum infection should always be considered as a cause of skin lesions in immunocompromised subjects. Physicians should be aware of the possibility of IRIS as a complication of successful antiretroviral therapy in HIV-infected patients with M. haemophilum infection.