Search

Dengue virus (DENV) is a major global health concern, causing millions of infections annually. Understanding the cellular response to DENV infection is crucial for developing effective therapies. This study provides an in-depth analysis of the cellular response to Dengue virus (DENV) infection, with a specific focus on the interplay between microRNAs (miRNAs), apoptosis, and viral load across different DENV serotypes. Utilizing a variety of cell lines infected with four DENV serotypes, the research methodically quantifies viral load, and the expression levels of miRNA-15, miRNA-16, and BCL2 protein, alongside measuring apoptosis markers. Methodologically, the study employs quantitative PCR for viral load and miRNA expression analysis, and Western blot for apoptosis and BCL2 detection, with a statistical framework that includes ANOVA and correlation analysis to discern significant differences and relationships. The findings reveal that despite similar viral loads across DENV serotypes, DENV-2 exhibits a marginally higher load. A notable upregulation of miRNA-15 and miRNA-16 correlates positively with increased viral load, suggesting their potential role in modulating viral replication. Concurrently, a marked activation of caspases 3 and 7, along with changes in BCL2 protein levels, underscores the role of apoptosis in the cellular response to DENV infection. Conclusively, the study enhances the understanding of miRNA involvement in DENV pathogenesis, highlighting miRNA-15 and miRNA-16 as potential regulatory agents in viral replication and apoptosis. These findings pave the way for further exploration into miRNA-based therapeutic strategies against DENV infection., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Stroke is one of the principal cerebrovascular diseases in human populations and contributes to a majority of the functional impairments in the elderly. Recent discoveries have led to the inclusion of electroencephalography (EEG) in the complementary prognostic evaluation of patients. The present study describes the EEG, behavioral, and histological changes that occur following cerebral ischemia associated with treatment by G1, a potent and selective G protein-coupled estrogen receptor 1 (GPER1) agonist in a rat model. Treatment with G1 attenuated the neurological deficits induced by ischemic stroke from the second day onward, and reduced areas of infarction. Treatment with G1 also improved the total brainwave power, as well as the theta and alpha wave activity, specifically, and restored the delta band power to levels similar to those observed in the controls. Treatment with G1 also attenuated the peaks of harmful activity observed in the EEG indices. These improvements in brainwave activity indicate that GPER1 plays a fundamental role in the mediation of cerebral injury and in the behavioral outcome of ischemic brain injuries, which points to treatment with G1 as a potential pharmacological strategy for the therapy of stroke., (© The Author(s) 2023. Published by Oxford University Press on behalf of American Association of Neuropathologists, Inc. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

This cross-sectional study evaluated the association between human exposure to mercury and cardiovascular risk using lipid profile (including apolipoproteins) and genetic analysis of Amazonian riverine population. Anthropometric data (gender, age, height, weight, blood pressure, and neck and waist circumferences) of the participants were recorded. Total mercury and methylmercury (MeHg) content were quantified in hair by ICP-MS and GC-pyro-AFS system. Polymorphisms rs662799, rs693, rs429358 and rs7412 (of genes of apolipoproteins A-V, B, and E at positions 112 and 158, respectively) were genotyped by real-time PCR. The population presented a dyslipidemia profile significantly correlated with high mercury levels. The apolipoprotein B/apolipoprotein A-I (ApoB/ApoA-I) index was also positively correlated with mercury, supporting a possible causal relationship. Allelic distributions were similar to those described in other populations, suggesting that genetic susceptibility may not have a significant role in the lipid alterations found in this work. This study demonstrated for the first time: i) the relationship between mercury exposure and cardiovascular risk-related apolipoproteins in humans, ii) the ApoB levels and the ApoB/ApoA-I index as the risk factors more strongly associated to the mercury-related dyslipidemia in humans, and iii) the prevalence of high/moderate risk of acute myocardial infarction in the vulnerable and chronically exposed-populations of the Amazon, in addition to the genotypic profile of the three most frequent polymorphisms in apolipoproteins of relevance for cardiovascular risk. This early detection of lipid alterations is essential to prevent the development of cardiovascular diseases (CVD), especially in chronically exposed populations such as those found in the Amazon. Therefore, in addition to provide data for the Minamata Convention implementation, our work is in line with the efforts joined by all members of the World Health Organization committed to reducing premature deaths originating from non-communicable diseases by 25% in 2025, including CVD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: This study verified the replication efficiency of the Rocio virus in a primary culture of mouse neural cells., Methods: Mixed primary cultures (neurons/glia) obtained from the brains of newborn isogenic BALB/c mice were inoculated with Rocio virus on the 7 th day of culture, and the development of cytopathogenic effects was monitored. The infection was confirmed via immunocytochemistry (anti-ROCV), while viral replication was quantified in infected primary cultures. The titration method used depended on the infection period., Results: Rocio virus efficiently infected primary cultured neural cells, with the highest viral titer causing cytopathic changes was observed at 2 days post infection. The virus-infected primary culture survived for up to 7 days post infection, and viral load quantitation showed viral replication kinetics compatible with the cell death kinetics of cultures., Conclusion: The findings of this study suggest that mouse neural cell primary cultures support Rocio virus replication and could be used as an alternative system for studying Flavivirus infection in the central nervous system.

Arboviruses, such as yellow fever virus (YFV), dengue virus (DENV), and chikungunya virus (CHIKV), present wide global dissemination and a pathogenic profile developed in infected individuals, from non-specific clinical conditions to severe forms, characterised by the promotion of significant lesions in different organs of the harbourer, culminating in multiple organ dysfunction. An analytical cross-sectional study was carried out via the histopathological analysis of 70 samples of liver patients, collected between 2000 and 2017, with confirmed laboratory diagnoses, who died due to infection and complications due to yellow fever (YF), dengue fever (DF), and chikungunya fever (CF), to characterise, quantify, and compare the patterns of histopathological alterations in the liver between the samples. Of the histopathological findings in the human liver samples, there was a significant difference between the control and infection groups, with a predominance of alterations in the midzonal area of the three cases analysed. Hepatic involvement in cases of YF showed a greater intensity of histopathological changes. Among the alterations evaluated, cell swelling, microvesicular steatosis, and apoptosis were classified according to the degree of tissue damage from severe to very severe. Pathological abnormalities associated with YFV, DENV, and CHIKV infections showed a predominance of changes in the midzonal area. We also noted that, among the arboviruses studied, liver involvement in cases of YFV infection was more intense., Competing Interests: The authors declare no conflicts of interest.

Ischemic stroke is one of the principal causes of morbidity and mortality around the world. The pathophysiological mechanisms that lead to the formation of the stroke lesions range from the bioenergetic failure of the cells and the intense production of reactive oxygen species to neuroinflammation. The fruit of the açaí palm, Euterpe oleracea Mart. (EO), is consumed by traditional populations in the Brazilian Amazon region, and it is known to have antioxidant and anti-inflammatory properties. We evaluated whether the clarified extract of EO was capable of reducing the area of lesion and promoting neuronal survival following ischemic stroke in rats. Animals submitted to ischemic stroke and treated with EO extract presented a significant improvement in their neurological deficit from the ninth day onward. We also observed a reduction in the extent of the cerebral injury and the preservation of the neurons of the cortical layers. Taken together, our findings indicate that treatment with EO extract in the acute phase following a stroke can trigger signaling pathways that culminate in neuronal survival and promote the partial recovery of neurological scores. However, further detailed studies of the intracellular signaling pathways are needed to better understand the mechanisms involved.

Yellow fever (YF) may cause lesions in different organs. There are no studies regarding the in situ immune response in the human lung and investigating immunopathological aspects in fatal cases can help to better understand the evolution of the infection. Lung tissue samples were collected from 10 fatal cases of human yellow fever and three flavivirus-negative controls who died of other causes and whose lung parenchymal architecture was preserved. In YFV-positive fatal cases, the main histopathological changes included the massive presence of diffuse alveolar inflammatory infiltrate, in addition to congestion and severe hemorrhage. The immunohistochemical analysis of tissues in the lung parenchyma showed significantly higher expression of E-selectin, P-selectin, ICAM-1, VCAM-1 in addition to cytokines such as IL-4, IL-10, IL-13, TNF- α, IFN-γ and TGF-β compared to the negative control. The increase in immunoglobulins ICAM-1 and VCAM-1 results in strengthening of tissue transmigration signaling. E-selectin and P-selectin actively participate in this process of cell migration and formation of the inflammatory infiltrate. IFN-γ and TNF-α participate in the process of cell injury and viral clearance. The cytokines IL-4 and TGF-β, acting in synergism, participate in the process of tissue regeneration and breakdown. The anti-inflammatory cytokines IL-4, IL-10 and IL-13 also act in the reduction of inflammation and tissue repair. Our study indicates that the activation of the endothelium aggravates the inflammatory response by inducing the expression of adhesion molecules and cytokines that contribute to the rolling, recruitment, migration and eliciting of the inflammatory process in the lung parenchyma, contributing to the fatal outcome of the disease., Competing Interests: The authors declare no conflict of interest.

Yellow fever (YF) is an infectious disease considered a public health problem in tropical and subtropical areas. YF has many pathophysiological events that are correlated with the host immune response. In this study, the in situ Th22 cytokine profile was evaluated. Liver tissue samples were collected from 21 YFV-positive patients who died of the disease and five flavivirus-negative controls who died of other causes and whose hepatic parenchyma architecture was preserved. Immunohistochemical (IHC) analysis of tissues in the hepatic parenchyma of YF cases showed significantly higher expression of interleukin (IL)-22, IL-13, tumour necrosis factor-alpha, and FGF basic (FGF b) in YFV-positive cases than that in flavivirus-negative controls. These results indicate that the response of Th22 cytokines emerges as an alternative for a better understanding of adaptive immunity in the hepatic parenchyma, highlighting the role of cytokines in the repair and suppressive responses in the immunopathogenesis of YFV infection., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Macrophages in the kidney play a pathogenic role in inflammation and fibrosis. Our study aimed to understand the polarisation of the M1 and M2 phenotypic profiles of macrophages in injured kidney tissue retrieved from fatal cases of yellow fever virus (YFV). A total of 11 renal tissue biopsies obtained from patients who died of yellow fever (YF) were analysed. To detect antibodies that promote the classical and alternative pathways of macrophage activation, immunohistochemical analysis was performed to detect CD163, CD68, inducible nitric oxide synthase (iNOS), arginase 1, interleukin (IL)-4, IL-10, interferon (IFN)-γ, IFN-β, tumour necrosis factor (TNF)-α, IL-13, and transforming growth factor (TGF)-β. There was a difference in the marker expression between fatal cases of YFV and control samples, with increased expression in the cortical region of the renal parenchyma. The immunoexpression of CD68 and CD163 receptors suggests the presence of activated macrophages migrating to infectious foci. The rise in IL-10, IL-4, and IL-13 indicated their potential role in the inactivation of the inflammatory macrophage response and phenotypic modulation of M2 macrophages. The altered expression of IFN-γ and IFN-β demonstrates the importance of the innate immune response in combating microorganisms. Our findings indicate that the polarisation of M1 and M2 macrophages plays a vital role in the renal immune response to YFV.

The early detection and diagnosis of deaths in free-ranging non-human primates (NHPs) are key points for the surveillance of Yellow Fever (YF) in Brazil. The histopathological identification of infectious diseases remains very useful and reliable in the screening and detection of emerging zoonotic diseases such as YF. We surveyed data records and liver slides stained with hematoxylin and eosin from the Epizootics Surveillance Network to control YF, Ministry of Health of Brazil, to evaluate histopathological hallmarks for the diagnosis of the YF virus infection. We selected natural fatal cases in NHPs from the genera Alouatta spp., Callithrix spp., and Sapajus spp. with a positive immunohistochemical assay for YF in liver samples. Our findings showed the full-spectrum YF-associated hepatic lesions in all NHPs, but some histopathological findings differed in the distribution and intensity between the three genera. In our study, South American NHPs showed significant differences in the YF-associated hepatic histopathological features compared to fatal cases reported in humans., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Yellow fever (YF) is an infectious and acute viral haemorrhagic disease that triggers a cascade of host immune responses. We investigated the Th17 cytokine profile in the liver tissue of patients with fatal YF. Liver tissue samples were collected from 26 deceased patients, including 21 YF-positive and 5 flavivirus-negative patients, with preserved hepatic parenchyma architecture, who died of other causes. Histopathological and immunohistochemical analysis were performed on the liver samples to evaluate the Th17 profiles (ROR-γ, STAT3, IL-6, TGF-β, IL-17A, and IL-23). Substantial differences were found in the expression levels of these markers between the patients with fatal YF and controls. A predominant expression of Th17 cytokine markers was observed in the midzonal region of the YF cases, the most affected area in the liver acinus, compared with the controls. Histopathological changes in the hepatic parenchyma revealed cellular damage characterised mainly by the presence of inflammatory cell infiltrates, Councilman bodies (apoptotic cells), micro/macrovesicular steatosis, and lytic and coagulative necrosis. Hence, Th17 cytokines play a pivotal role in the immunopathogenesis of YF and contribute markedly to triggering cell damage in patients with fatal disease outcomes.

Yellow fever (YF), a non-contagious infectious disease, is endemic or enzootic to the tropical regions of the Americas and Africa. Periodic outbreaks or epidemics have a significant impact on public health. Programmed cell death, or apoptosis, is generally characterised by distinct morphological changes and energy-dependent biochemical pathways. In this study, we performed immunohistochemistry analysis to identify and quantify proteases and protein targets involved in the cascade that triggers apoptosis in YF virus (YFV)-infected human hepatocytes. Liver tissue samples were collected from 26 individuals, among whom 21 were diagnosed as YF-positive, and five were flavivirus-negative and died due to other causes. The histopathological alterations in YFV-positive cases were characterised by the presence of apoptotic bodies, steatosis, cellular swelling, and extensive necrosis and haemorrhage in the hepatic lobules. Additionally, we observed an abundance of inflammatory infiltrates in the portal tract. The expression of various apoptotic markers in the hepatic parenchyma, including CASPASE 3, CASPASE 8, BAX, FAS, FASL, GRANZYME B, and SURVIVIN, differed between YFV-positive cases and controls. Collectively, this study confirmed the complexity of YFV infection-induced apoptosis in situ. However, our data suggest that apoptosis in liver parenchyma lesions may significantly contribute to the pathogenesis of fatal YF in humans.

Background: Some studies have suggested the importance of vitamin D [25(OH)D] in malaria clinical practice. The prevalence of 25(OH)D deficiency in the Amazon population is not well known, and there are few studies in patients with malaria. This study aimed to evaluate 25(OH)D serum levels in patients with malaria and determine their relationships with epidemiological, clinical, laboratory, and parasitemia data., Methods: An analytical cross-sectional study of 123 patients with malaria and 122 individuals without malaria was performed in Itaituba, Pará, Brazil, from January 2018 to October 2019, by evaluating sociodemographic, clinical-epidemiological, parasitological, and laboratory data and adopting a 5% significance level. Parametric tests (Student's t-test), non-parametric tests (Mann-Whitney U), and Spearman's correlation ([rs], for non-parametric variables) were used according to the nature of the distribution of the variables. For the qualitative variables, Pearson's chi-square test, Fisher's exact test, and the G test were used. Spearman's correlation was used to compare the results of the 25(OH)D levels and blood counts performed among patients and the control group., Results: Malaria patients residing in a mining area had 25(OH)D serum levels that were significantly lower than those in the control group residing in the mining area, though both were within normal levels. Red blood cell counts had an inverse correlation with parasitemia (Plasmodium falciparum), and platelet levels had an inverse correlation with parasitemia (Plasmodium vivax). 25(OH)D deficiency was evidenced in Itaituba, in the state of Pará, which is an endemic area of malaria in the Amazon region.

The present study describes the electroencephalographic changes that occur during cerebral ischemia and reperfusion in animals submitted to transient focal cerebral ischemia by middle cerebral artery occlusion (MCAO) for 30 min. For this, male Wistar rats were divided into two groups ( n = 6 animals/group): (1) sham (control) group, and (2) ischemic/reperfusion group. The quantitative electroencephalography (qEEG) was recorded during the ischemic and immediate reperfusion (acute) phases, and then once a day for 7 days after the MCAO (subacute phase). The acute phase was characterized by a marked increase in the relative delta wave band power ( p < 0.001), with a smaller, but significant increase in the relative alpha wave bandpower in the ischemic stroke phase, in comparison with the control group ( p = 0.0054). In the immediate reperfusion phase, however, there was an increase in the theta, alpha, and beta waves bandpower ( p < 0.001), but no alteration in the delta waves ( p = 0.9984), in comparison with the control group. We also observed high values in the delta/theta ratio (DTR), the delta/alpha ratio (DAR), and the (delta+theta)/(alpha+beta) ratio (DTABR) indices during the ischemia ( p < 0.05), with a major reduction in the reperfusion phase. In the subacute phase, the activity of all the waves was lower than that of the control group ( p < 0.05), although the DTR, DAR, and DTABR indices remained relatively high. In conclusion, early and accurate identification of decreased delta wave bandpower, DTR, DAR, and DTABR indices, and an increase in the activity of other waves in the immediate reperfusion phase may represent an important advance for the recognition of the effectiveness of reperfusion therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ferreira, Mattos, Jóia de Mello, Martins-Filho, Costa, Yamada, Hamoy and Lopes.)

The Guama virus (GMAV) is a member of Peribunyaviridae family, Orthobunyavirus genus. Several strains of the virus were isolated in South and Central Americas from several hosts, such as humans, wild animals, including nonhuman primates, wild rodents and mosquitoes as well as mice used as sentinels. The virus is able to cause febrile disease in humans. Here we describe for the first time pathologic and biochemical findings in golden hamsters (Mesocricetus auratus) infected with the prototype GMAV. Blood and organs of infected and control animals were collected every 24 h after infection from the 1st to the 7th day post infection (dpi) and at 21 dpi when experiment was ended. The tissues were processed for histopathology and immunohistochemistry. The blood and serum were used to determine viremia and biochemical markers plus to detect anti-GMAV antibodies. The viremia was early detected already on the 1st dpi and it was no longer detected on the 3rd dpi. Total anti-GMAV antibodies were detected from the 6th dpi. Hepatic markers as ALT of infected animals were increased and showed statistically significant difference in comparison with control animals, indicating damage of the liver; indeed the liver was the most affected organ, but other organs presented lesions and positive GMAV immunostaining as brain, lung, liver, spleen, and kidney. Our findings indicate that golden hamsters are a good animal model for experimental infection of the GMAV., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Serological evidence of West Nile virus (WNV) infection has been reported in different regions of Brazil from equine and human hosts but the virus had never been isolated in the country., Objectives: We sought to identify the viral etiology of equine encephalitis in Espírito Santo state., Methods: We performed viral culture in C6/36 cells, molecular detection of WNV genome, histopathology and immunohistochemistry from horse cerebral tissue. We also carried out sequencing, phylogenetic analysis and molecular clock., Findings: Histopathologic analysis from horse cerebral tissue showed injury related to encephalitis and WNV infection was confirmed by immunohistochemistry. The virus was detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR) from brain tissue and subsequently isolated in C6/36 cells. WNV full-length genome was sequenced showing the isolated strain belongs to lineage 1a. The molecular clock indicated that Brazilian WNV strain share the same common ancestor that were circulating in US during 2002-2005., Main Conclusions: Here we report the first isolation of WNV in Brazil from a horse with neurologic disease, which was clustered into lineage 1a with others US WNV strains isolated in beginning of 2000's decade.

Zika virus (ZIKV) has caused substantial concern worldwide owing to its association with severe birth defects, such as microcephaly and other congenital malformations. Inflammasomes, i.e., multi-protein complexes that induce inflammation and pyroptosis, are predicted to contribute to the immune response to this flavivirus. Accordingly, in this study, the in situ inflammasome response was evaluated in fatal cases of ZIKV-linked microcephaly. Brain tissue samples were collected from eight babies, including four ZIKV-positive microcephalic neonates who died after birth and four flavivirus-negative neonatal controls who died of other causes and whose central nervous system (CNS) architecture was preserved. In the ZIKV-positive newborn/stillbirth babies, the major histopathological alterations included atrophy of the cortical layer, a predominance of mononuclear cell infiltration in the Virchow-Robin space, neuronal necrosis, vacuolization and neuronal degeneration, neuronophagy, and gliosis. An immunohistochemical analysis of tissues in the neural parenchyma showed significantly higher expression of the receptors NLRP1, NLRP3, and AIM2, cytokines IL-1β, IL-18, and IL-33, and enzymes caspase 1, iNOS, and arginase 1 in ZIKV-positive microcephaly cases than in flavivirus-negative controls. These results suggest that inflammasome activation can aggravate the neuroinflammatory response and consequently increase CNS damage in neonates with fetal neural ZIKV infection and microcephaly., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Zika virus (ZIKV) is a single-stranded positive-sense RNA flavivirus that possesses a genome approximately 10.7 Kb in length. Although pro-inflammatory and anti-inflammatory cytokines and apoptotic markers belonging to the extrinsic and intrinsic pathways are suggested to be involved in fatal cases of ZIKV-induced microcephaly, their exact roles and associations are unclear. To address this, brain tissue samples were collected from 10 individuals, five of whom were diagnosed as ZIKV positive with microcephaly and a further five were flavivirus-negative controls that died because of other causes. Examination of material from the fatal cases of microcephaly revealed lesions in the cerebral cortex, edema, vascular proliferation, neuronal necrosis, gliosis, neuronophagy, calcifications, apoptosis, and neuron loss. The expression of various apoptosis markers in the neural parenchyma, including FasL, FAS, BAX, BCL2, and caspase 3 differed between ZIKV-positive cases and controls. Further investigation of type 1 and 2 helper T-cell cytokines confirmed a greater anti-inflammatory response in fatal ZIKV-associated microcephaly cases. Finally, an analysis of the linear correlation between tumor necrosis factor-α, IL-1β, IL-4, IL-10, transforming growth factor-β, and IL-33 expression and various apoptotic markers suggested that the immune response may be associated with the apoptotic phenomenon observed in ZIKV-induced microcephaly., (Copyright © 2018 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Children and adolescents are at great risk for developing iron deficiency anaemia worldwide. In the tropical areas, malaria and intestinal parasites may also play an important role in anaemia pathogenesis. This study aimed at evaluating clinical and immunological aspects of anaemia in children and adolescents with Plasmodium vivax malaria, in the Pará State, Brazil. A longitudinal study was performed in two Reference Centers for malaria diagnosis in the Brazilian Amazon in children and adolescents with malaria (n = 81), as compared to a control group (n = 40). Patients had blood drawn three times [before treatment (D0), after treatment (D7) and at the first cure control (D30)] and hemogram, autoantibody analysis (anticardiolipin, antibodies against normal RBC membrane components) and cytokine studies (TNF and IL-10) were performed. Stool samples were collected for a parasitological examination. Malaria patients had a 2.7-fold greater chance of anaemia than the control group. At D0, 66.1% of the patients had mild anaemia, 30.5% had moderate and 3.5% had severe anaemia. Positivity to intestinal helminths and/or protozoa at stool examinations had no influence on anaemia. Patients had significantly lower levels of plasmatic TNF than control individuals at D0. Low TNF levels were more prevalent among patients with moderate/severe anaemia than in those with mild anaemia and among anaemic patients than in anaemic controls. TNF levels were positively correlated with the haemoglobin rates and negatively correlated with the interval time elapsed between the onset of symptoms and diagnosis. Both plasma TNF levels and haemoglobin rates increased during the follow-up period. The IL-10 levels were lower in patients than in the controls at day 0 and decreased thereafter up to the end of treatment. Only the anti-anticardiolipin autoantibodies were associated with moderate/severe anaemia and, possibly by reacting with the parasite glycosylphosphatidylinositol (a powerful stimulator of TNF production), may have indirectly contributed to decrease the TNF levels, which could be involved in the malarial vivax anaemia of these children and adolescents. More studies addressing this issue are necessary to confirm these findings and to add more information on the multifactorial pathogenesis of the malarial anaemia., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Zika virus (ZIKV) has recently caused a pandemic disease, and many cases of ZIKV infection in pregnant women resulted in abortion, stillbirth, deaths and congenital defects including microcephaly, which now has been proposed as ZIKV congenital syndrome. This study aimed to investigate the in situ immune response profile and mechanisms of neuronal cell damage in fatal Zika microcephaly cases. Brain tissue samples were collected from 15 cases, including 10 microcephalic ZIKV-positive neonates with fatal outcome and five neonatal control flavivirus-negative neonates that died due to other causes, but with preserved central nervous system (CNS) architecture. In microcephaly cases, the histopathological features of the tissue samples were characterized in three CNS areas (meninges, perivascular space, and parenchyma). The changes found were mainly calcification, necrosis, neuronophagy, gliosis, microglial nodules, and inflammatory infiltration of mononuclear cells. The in situ immune response against ZIKV in the CNS of newborns is complex. Despite the predominant expression of Th2 cytokines, other cytokines such as Th1, Th17, Treg, Th9, and Th22 are involved to a lesser extent, but are still likely to participate in the immunopathogenic mechanisms of neural disease in fatal cases of microcephaly caused by ZIKV.

Background: Zika virus (ZIKV) was first detected in Brazil in May 2015 and the country experienced an explosive epidemic. However, recent studies indicate that the introduction of ZIKV occurred in late 2013. Cases of microcephaly and deaths associated with ZIKV infection were identified in Brazil in November, 2015., Objectives: To determine the etiology of three fatal adult cases., Study Design: Here we report three fatal adult cases of ZIKV disease. ZIKV infection in these patients was confirmed by cells culture and/or real-time reverse transcriptase polymerase chain reaction (RT-qPCR) and by antigen detection using immunohistochemical assay. Samples of brain and other selected organs taken at autopsy from three patients were also analyzed by histopathological and immunohistological examination., Results: The first patient, a 36-year-old man with lupus and receiving prednisone therapy, developed a fulminant ZIKV infection. At autopsy, RT-qPCR of blood and tissues was positive for ZIKV RNA, and the virus was cultured from an organ homogenate. The second patient, a previously healthy female, 16 years of age, presented classic symptoms of Zika fever, but later developed severe thrombocytopenia, anemia and hemorrhagic manifestations and died. A blood sample taken on the seventh day of her illness was positive RT-PCR for ZIKV RNA and research in the serum was positive for antinuclear factor fine speckled (1/640), suggesting Evans syndrome (hemolytic anemia an autoimmune disorder with immune thrombocytopenic purpura) secondary to ZIKV infection. The third patient was a 20-year-old woman hospitalized with fever, pneumonia and hemorrhages, who died on 13days after admission. Histopathological changes were observed in all viscera examined. ZIKV antigens were detected by immunohistochemistry in viscera specimens of patients 1 and 3. These three cases demonstrate other potential complications of ZIKV infection, in addition to microcephaly and Guillain-Barre syndrome (GBS), and they suggest that individuals with immune suppression and/or autoimmune disorders may be at higher risk of developing severe disease, if infected with ZIKV., Competing Interests: Authors declare they have not conflict of interest., (Copyright © 2016 Elsevier B.V. All rights reserved.)