Project description:Arthropod-borne viruses (arboviruses) represent a threat to global public health, especially in the tropical and subtropical regions of the world. More than 150 arboviruses can infect humans; they cause mainly febrile illness, although hemorrhagic complications and diseases affecting the central nervous system (SNC) can also be observed. Arboviruses represent a threat to Brazil and, therefore, a permanent surveillance of these viruses is required to timely reduce the risk of epidemic outbreaks. The Brazilian Amazon region is where the highest number of arboviruses has been detected in the world. Besides, malaria is also endemic in the Amazon region, with a significant predominance of Plasmodium vivax. It is often difficult to differentiate between malaria and arboviral diseases, as they share similar clinical features and laboratory findings, mainly undifferentiated fever. This study aimed to estimate possible viral etiology in patients with febrile syndrome negative for Plasmodium infection, in the Brazilian Amazon. We initially analyzed serum samples of 124 participants with a DNA microarray platform designed for the detection of arboviruses and viruses transmitted by small mammals, but no virus was detected. Then, the serum samples of 76 participants were analyzed with a deep New Generation Sequencing, which showed evidence of the presence of only one arbovirus, the Zika virus in only one pool of 9 serum samples. This result is in contrast with our hypothesis, showing that arboviruses are not frequent in suspected malaria cases in Manaus, Brazil. Other viruses instead of arboviruses were found in this study. Primate erythrovirus 1 was the virus most frequently found virus in the suspected malaria patients, followed by Enterobacteria phage lambda. Besides, we detected, in a lower frequency, the Pegivirus C. In addition to the exogenous viruses, we also detected human endogenous retrovirus in all pools. Due to the high number of viruses that are important in the differential diagnosis of malaria, cost-effective and simple high throughput methods are required, helping molecular surveillance of misdiagnosed viral infections. Further studies with more robust sample sizes in other areas in the Amazon are needed.

Project description:Genome wide DNA methylation profiling of isolated monocyte samples from healthy Kenyan children, the same children during an episode of acute malaria, healthy Kenyan adults, and healthy adults from the United States. The Illumina Infinium MethylationEPIC BeadChip microarray was used to obtain DNA methylation profiles across approximately 860,000 CpGs in negatively selected monocyte samples. Samples included monocytes from 8 children from western Kenya obtained while healthy and matching samples from the same 8 Kenyan children obtained during an episode of acute uncomplicated Plasmodium falciparum malaria, 8 healthy malaria-immune adults from western Kenya, and 8 healthy malaria-naive adults from the US. Abstract -- Background: Age-related changes in adaptive and innate immune cells have been associated with a decline in effective immunity and chronic, low-grade inflammation. Epigenetic, transcriptional, and functional changes in monocytes occur with aging, though most studies to date have focused on differences between young adults and the elderly in populations with European ancestry; few data exist regarding changes that occur in circulating monocytes during the first few decades of life or in African populations. We analyzed DNA methylation profiles, cytokine production, and inflammatory gene expression profiles in monocytes from young adults and children from western Kenya. Results: We identified several hypo- and hyper-methylated CpG sites in monocytes from Kenyan young adults vs. children that replicated findings in the current literature of differential DNA methylation in monocytes from elderly persons vs. young adults across diverse populations. Differentially methylated CpG sites were also noted in gene regions important to inflammation and innate immune responses. Monocytes from Kenyan young adults vs. children displayed increased production of IL-8, IL-10, and IL-12p70 in response to TLR4 and TLR2/1 stimulation as well as distinct inflammatory gene expression profiles. Conclusions: These findings complement previous reports of age-related methylation changes in isolated monocytes and provide novel insights into the role of age-associated changes in innate immune functions.

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