Evaluation of the Antiproliferative Potential of Yellow Jaboticaba (Myrciaria glazioviana) Extracts Against Human Cervical Cancer (HeLa cells line) and the Analysis of Their Chemical Composition by HPLC-HRESIMS.

Cervical cancer is a specific type of cancer that affects women around the world, with an incidence of 604 thousand new cases per year and 341 thousand deaths. There is a high demand for new effective antineoplastic drugs with few side effects. In this sense, recent research highlights the potential of compounds of natural origin in treating and preventing different types of cancer. Myrciaria glazioviana is a Brazilian native species belonging to the Myrtaceae family, which has previously described biological activities such as antimicrobial, anti-inflammatory, and antioxidant properties. This study aims to evaluate the anticancer activity of the dichloromethane extract (MGD) and ethyl acetate extract (MGA) of M. glazioviana leaves against human cervical cancer cell line (HeLa), as well as to identify their bioactive compounds. Using HPLC-HRESIMS technique, ten compounds were characterized in both samples: quinic acid, ellagic acid, Tri-O-methyl ellagic acid, two derivatives of Tetra-O-methyl flavellagic acid, quercetrin, Di-O-methyl ellagic acid, and three derivatives of pentamethyl coruleoellagic acid. Through MTT assays using HeLa cells and NIH/3T3 cells, it was observed that MGD and MGA were selective against tumor cells, with IC50 values of 24.31 and 12.62 µg/mL, respectively. The samples induced the tumor cell death by apoptosis, as evidenced by the activation of caspases 3/7, cell shrinkage, and pyknotic nuclei. Both samples were also able to inhibit the migration of HeLa cells after 24 hours of treatment, indicating a potential antimetastatic effect. Therefore, the present research highlights the antiproliferative and antimigratory potential of this species against HeLa cells.

Investigation of cytokine polymorphisms on viral infections after renal transplantation exhibit association between IFN-γ +874 A > T and CMV manifestations.

We investigated the effects of TNF-α, IFN-γ, IL-10 polymorphisms on viral infections (CMV, BKPyV, HHV-6, EBV) after renal transplantation. IFN-γ+874 A > T (lower IFN production) was associated with CMV disease (p = .039) in patients under mycophenolate-based therapy and graft failure (p = .025). This study underscores the role of IFN-γ+874 SNP in CMV infection.

Myrciaria Genus: Bioactive Compounds and Biological Activities.

The Myrtaceae family is of angiosperms, imposing its size and economic, cultural, and scientific importance. The genus Myrciaria, belonging to this family, has 33 species currently accepted, many of which are research targets aimed at elucidating their bioactive compounds and biological activities. Most species of the Myrciaria genus have terpenes in their composition, mainly mono and sesquiterpenes, and phenolic compounds such as tannins, phenolic acids, and flavonoids. Other secondary metabolites are also observed, such as alkaloids, steroids, coumarins, saponins, and naphthoquinones. These bioactive compounds are closely related to these species' most diverse biological activities: antioxidant, anti-inflammatory, analgesic, antiproliferative, antimicrobial, antiparasitic, insecticide, metabolic, protective, and nutraceutical. This work aims to provide a review of secondary metabolites and medicinal properties related to the genus Myrciaria, thus stimulating further studies on the species of this genus.

Coinfection of domestic felines by distinct Sporothrix brasiliensis in the Brazilian sporotrichosis hyperendemic area.

Microbial interactions may impact patient's diagnosis, prognosis and treatment. Sporotrichosis is a hyperendemic neglected zoonosis in Brazil, caused by Sporothrix brasiliensis. Four pairs of clinical isolates of Sporothrix were recovered from four diseased cats (CIM01-CIM04, two isolates per animal) raising the possibility of coinfection in a sporotrichosis hyperendemic area, Brazil. Each isolate of the pair had distinct pigmentation in mycological culture, and was designated as "Light" or "Dark", for low and high pigmentation, respectively. Dark isolates reacted strongly with monoclonal antibodies to melanin (p ≤ 0.05) by both ELISA and FACS quantitation, and displayed a ring pattern with some regions exhibiting higher punctuated labeling at cell wall by immunofluorescence. In turn, Light isolates reacted less intensely, with few and discrete punctuated labeling at the cell wall. PCR identified all isolates as S. brasiliensis, MAT1-2 idiomorph. Sequencing of ß-tubulin and calmodulin genes followed by phylogenetic analysis placed all eight isolates within the same cluster as others from the Brazilian hyperendemic area. The ability of these strains to stimulate cytokine production by human PBMCs (Peripheral blood mononuclear cells) was also analyzed. CIM01 and CIM03 Light and Dark isolates showed similar cytokine profiles to the control strain, while CIM02 and CIM04 behaved differently (p < 0.001), suggesting that differences in the surface of the isolates can influence host-fungus interaction. MICs for amphotericin B, terbinafine, caspofungin, micafungin, itraconazole, fluconazole, and voriconazole were obtained (CLSI M38-A2/M27-A3). Pairwise comparisons showed distinct MICs between Sporothrix Light and Dark isolates, higher than at least two-fold dilutions, to at least one of the antifungals tested. Isolates from the same pair displayed discrepancies in relation to fungistatic or fungicidal drug activity, notably after itraconazole exposure. Since S. brasiliensis Light and Dark isolates show disparate phenotypic parameters it is quite possible that coinfection represents a common occurrence in the hyperendemic area, with potential clinical implications on feline sporotrichosis dynamics. Alternatively, future studies will address if this specie may have, as reported for other fungi, broad phenotypic plasticity.

Chloroquine and mefloquine resistance profiles are not related to the circumsporozoite protein (CSP) VK210 subtypes in field isolates of Plasmodium vivax from Manaus, Brazilian Amazon.

BACKGROUND: The central repetitive region (CRR) of the Plasmodium vivax circumsporozoite surface protein (CSP) is composed of a repetitive sequence that is characterised by three variants: VK210, VK247 and P. vivax-like. The most important challenge in the treatment of P. vivax infection is the possibility of differential response based on the parasite genotype. OBJECTIVES: To characterise the CSP variants in P. vivax isolates from individuals residing in a malaria-endemic region in Brazil and to profile these variants based on sensitivity to chloroquine and mefloquine. METHODS: The CSP variants were determined by sequencing and the sensitivity of the P. vivax isolates to chloroquine and mefloquine was determined by Deli-test. FINDINGS: Although five different allele sizes were amplified, the sequencing results showed that all of the isolates belonged to the VK210 variant. However, we observed substantial genetic diversity in the CRR, resulting in the identification of 10 different VK210 subtypes. The frequency of isolates that were resistant to chloroquine and mefloquine was 11.8 and 23.8%, respectively. However, we did not observe any difference in the frequency of the resistant isolates belonging to the VK210 subtypes. MAIN CONCLUSION: The VK210 variant is the most frequently observed in the studied region and there is significant genetic variability in the CRR of the P. vivax CSP. Moreover, the antimalarial drug sensitivity profiles of the isolates does not seem to be related to the VK210 subtypes.

Domestic feline contribution in the transmission of Sporothrix in Rio de Janeiro State, Brazil: a comparison between infected and non-infected populations.

BACKGROUND: Sporotrichosis is a neglected zoonosis caused by pathogenic fungi belonging to the Sporothrix schenckii complex. In Rio de Janeiro state, this disease reached an epidemic status with over 4700 domestic felines and around 4000 humans affected since the mid-90s. The present study evaluated clinical and epidemiological aspects and also the frequency of colonization and infection by these fungi in healthy cats and among those with suspicious cutaneous lesions, inhabiting four Rio de Janeiro state distinct areas. RESULTS: Three hundred and seventy-one cats were included in two groups: 175 healthy cats [CRG] and 196 cats showing lesions suggesting sporotrichosis [SSG]. Mycological diagnosis allowed SSG animals to be divided in positive [104 cats; +SG] and negative [92 cats; -SG] groups. Nails, oral mucosa and lesions swabs were submitted to culture and potential colonies were subculture for micromorphologycal analysis, dimorphism and molecular tests. In the CRG, only one cat was colonized in the oral cavity [0.57%]; in the -SG group, four animals showed colonization of the nail and/or oral cavity [4.3%]; while the highest frequency of colonization [39.4%] was observed in the +SG. All molecularly typed isolates were identified as S. brasiliensis. CONCLUSION: The results obtained here indicate that healthy cats have a minor role in sporotrichosis transmission within the state of Rio de Janeiro. Conversely, a higher participation of diseased feline in sporotrichosis transmission was evidenced, especially by the colonization of their oral cavity. Sporothrix brasiliensis equally affects and colonizes animals from distinct Rio de Janeiro state areas. Thus, we hypothesize that sporotrichosis is a uniform endemic throughout the state, whose transmission depends mainly on the contact with cats with sporotrichosis. Since Rio de Janeiro displays a world unique epidemic model of the disease, not fully understood, data on the infected and non-infected animals can be of major importance for future strategies of sporotrichosis prevention and control. Finally, considering the importance of the current concept of "one health", the experience here observed can be helpful for distinct epizootias and/or zoonosis.

Cytokine gene polymorphisms are not associated with anti-PvDBP, anti-PvAMA-1 or anti-PvMSP-119 IgG antibody levels in a malaria-endemic area of the Brazilian Amazon.

BACKGROUND: The immune response against Plasmodium vivax immunogenic epitopes is regulated by pro- and anti-inflammatory cytokines that determine antibody levels and class switching. Cytokine gene polymorphisms may be responsible for changes in the humoral immune response against malaria. The aim of this study was to evaluate whether polymorphisms in the TNFA, IFNG and IL10 genes would alter the levels of anti-PvAMA1, PvDBP and -PvMSP-119 IgG antibodies in patients with vivax malaria. METHODS: Samples from 90 vivax malaria-infected and 51 uninfected subjects from an endemic area of the Brazilian Amazon were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to identify polymorphisms of the genes TNFA (-1031T > C, -308G > A, -238G > A), IFNG (+874T > A) and IL10 (-819C > T, -592C > A). The levels of total IgG against PvAMA1, PvDBP and PvMSP-119 were determined using an enzyme-linked immunosorbent assay (ELISA). Associations between the polymorphisms and the antibody response were assessed by means of logistic regression models. RESULTS: No significant differences were found in the levels of IgG antibodies against the PvAMA-1, PvDBP or PvMSP-119 proteins in relation to the studied polymorphisms. CONCLUSIONS: Although no associations were found among the evaluated genotypes and alleles and anti-merozoite IgG class P. vivax antibody levels, this study helps elucidate the immunogenic profile involved in the humoral immune response in malaria.

Frequency of TNFA, INFG, and IL10 Gene Polymorphisms and Their Association with Malaria Vivax and Genomic Ancestry.

Polymorphisms in cytokine genes can alter the production of these proteins and consequently affect the immune response. The trihybrid heterogeneity of the Brazilian population is characterized as a condition for the use of ancestry informative markers. The objective of this study was to evaluate the frequency of -1031T>C, -308G>A and -238G>A TNFA, +874 A>T IFNG and -819C>T, and -592C>A IL10 gene polymorphisms and their association with malaria vivax and genomic ancestry. Samples from 90 vivax malaria-infected individuals and 51 noninfected individuals from northern Brazil were evaluated. Genotyping was carried out by using ASO-PCR or PCR/RFLP. The genomic ancestry of the individuals was classified using 48 insertion/deletion polymorphism biallelic markers. There were no differences in the proportions of African, European, and Native American ancestry between men and women. No significant association was observed for the allele and genotype frequencies of the 6 SNPs between malaria-infected and noninfected individuals. However, there was a trend toward decreasing the frequency of individuals carrying the TNF-308A allele with the increasing proportion of European ancestry. No ethnic-specific SNPs were identified, and there was no allelic or genotype association with susceptibility or resistance to vivax malaria. Understanding the genomic mechanisms by which ancestry influences this association is critical and requires further study.

Humoral immune responses against the malaria vaccine candidate antigen Plasmodium vivax AMA-1 and IL-4 gene polymorphisms in individuals living in an endemic area of the Brazilian Amazon.

BACKGROUND: Several studies have recently demonstrated that the immune responses against malaria is governed by different factors, including the genetic components of the host. The IL-4 gene appears to be a strong candidate factor because of its role in the regulation of the Th2 response. The present study investigated the role of IL-4 polymorphisms in the development of IgG antibodies against PvAMA-1 and the IL-4 levels in individuals infected with Plasmodium vivax in a malaria endemic area in the Brazilian Amazon. METHODS: The study sample included 83 patients who were diagnosed with P. vivax infection using thick smear and confirmed by nested-PCR. The IL-4 -590C>T and IL-4 -33C>T polymorphisms were genotyped by PCR-RFLP, and the intron 3 VNTR was genotyped by PCR. A standardised ELISA protocol was used to measure the total IgG against PvAMA-1. The cytokine/chemokine levels were measured using a Milliplex multiplex assay (Millipore). All of the subjects were genotyped with 48 ancestry informative markers to determine the proportions of African, European and Amerindian ancestry using STRUCTURE software. RESULTS: Of the 83 patients, 60 (73%) produced IgG antibodies against PvAMA-1. A significant decrease in the percentage of respondents was observed among the primo-infected individuals. No significant differences were observed in the frequencies of genotypes and haplotypes among individuals who were positive or negative for IgG antibodies against PvAMA-1. Furthermore, no significant correlation was observed between the IL-4 polymorphisms, antibody levels, IL-4 levels, and parasitemia. CONCLUSIONS: This study indicated that the polymorphisms identified in the IL-4 gene are not likely to play a role in the regulation of the antibody response against PvAMA-1 and IL-4 production in vivax malaria.

Clinical and epidemiological profiles of individuals with drug-resistant tuberculosis.

Drug-resistant tuberculosis (TB) is a growing global threat. Approximately 450,000 people developed multidrug-resistant TB worldwide in 2012 and an estimated 170,000 people died from the disease. This paper describes the sociodemographic, clinical-epidemiological and bacteriological aspects of TB and correlates these features with the distribution of anti-TB drug resistance. Mycobacterium tuberculosis (MT) cultures and drug susceptibility testing were performed according to the BACTEC MGIT 960 method. The results demonstrated that MT strains from individuals who received treatment for TB and people who were infected with human immunodeficiency virus were more resistant to TB drugs compared to other individuals (p < 0.05). Approximately half of the individuals received supervised treatment, but most drug-resistant cases were positive for pulmonary TB and exhibited positive acid-fast bacilli smears, which are complicating factors for TB control programs. Primary healthcare is the ideal level for early disease detection, but tertiary healthcare is the most common entry point for patients into the system. These factors require special attention from healthcare managers and professionals to effectively control and monitor the spread of TB drug-resistant cases.

The evolutionary history of Plasmodium vivax as inferred from mitochondrial genomes: parasite genetic diversity in the Americas.

Plasmodium vivax is the most prevalent human malaria parasite in the Americas. Previous studies have contrasted the genetic diversity of parasite populations in the Americas with those in Asia and Oceania, concluding that New World populations exhibit low genetic diversity consistent with a recent introduction. Here we used an expanded sample of complete mitochondrial genome sequences to investigate the diversity of P. vivax in the Americas as well as in other continental populations. We show that the diversity of P. vivax in the Americas is comparable to that in Asia and Oceania, and we identify several divergent clades circulating in South America that may have resulted from independent introductions. In particular, we show that several haplotypes sampled in Venezuela and northeastern Brazil belong to a clade that diverged from the other P. vivax lineages at least 30,000 years ago, albeit not necessarily in the Americas. We propose that, unlike in Asia where human migration increases local genetic diversity, the combined effects of the geographical structure and the low incidence of vivax malaria in the Americas has resulted in patterns of low local but high regional genetic diversity. This could explain previous views that P. vivax in the Americas has low genetic diversity because these were based on studies carried out in limited areas. Further elucidation of the complex geographical pattern of P. vivax variation will be important both for diversity assessments of genes encoding candidate vaccine antigens and in the formulation of control and surveillance measures aimed at malaria elimination.

Measuring climate change's impact on different sugarcane varieties production in the South of Goiás.

A crucial aspect analysed during the last years, aiming to improve sugarcane production, is the impact of climate change on sugarcane productivity. One of the strategies to mitigate climate change's impact on sugarcane yield is the development of new varieties known to positively affect crop production. This paper analysed how climate change impacts sugarcane production regarding the different planted varieties. Data regarding sugarcane harvest were collected from a cooperative in the south of Goiás state-Brazil, the second biggest national sugarcane producer. Results indicate that climate impact on sugarcane yield is irrelevant when controlling for different varieties. Considering the results presented in this work, the Brazilian government should keep the incentives for the development of new sugarcane varieties and, at the same time, spur sugarcane producers to use the new sugarcane varieties. The results imply that if the variety is correctly chosen, sugarcane can be produced without harming the environment, contributing to reaching SDG 15. Moreover, it is less probable that an adverse climatic event will destroy the planted area, preventing sugarcane producers from severe loss and contributing to achieving SDGs number 1 and 2.

Case Report: Osteomyelitis Due to Sporothrix brasiliensis in Two Immunocompetent Patients Requiring Surgical Amputation.

Sporotrichosis is the most frequent subcutaneous mycosis in Latin America. Sporothrix brasiliensis is the most virulent species, responsible for the majority of human and animal cases in Brazil. Osteomyelitis was described as a potential comorbidity of S. brasiliensis infection; however, surgical amputation resulting from an extracutaneous form is a rare outcome. In such cases, immunodeficiency and alcoholism must be investigated. We present two unusual cases of surgical amputation as a severe morbidity resulting from osteomyelitis by S. brasiliensis in immunocompetent nonalcoholic patients.

Spatio-temporal six-year retrospective study on dermatophytosis in Rio de Janeiro, Southeast Brazil: A tropical tourist locality tale.

Trichophyton, Microsporum, Nannizzia and Epidermophyton genera cause dermatophytosis, the most common and highly contagious infectious skin disease. Rio de Janeiro is one of the most visited cities in the Southern Hemisphere, located in the most visited state of Brazil. This retrospective study investigated epidemiological and laboratorial aspects of dermatophytosis in Rio de Janeiro state, Brazil, by using spatiotemporal analysis. More than half of all individuals were infected by one or more dermatophytes. A variation between 18 and 106 years-old of the studied population was verified, and women more frequently affected. Patients were more frequently infected by Trichophyton spp., most of them T. rubrum, followed by T. mentagrophytes. M. canis and N. gypsea were more frequently isolated in the age group between 40 and 60 years old, while T. rubrum predominates among younger patients. All species presented homogeneous distribution while T. tonsurans appears to be restricted to the Rio de Janeiro capital and E. floccosum to the municipality of Macaé (190 Km apart from RJ). Rio de Janeiro state presented spatial clusters of dermatophytosis with high density in Guanabara Bay (E. floccosum, M. canis, N. gypsea, T. tonsurans) and Niterói (T. rubrum, T. mentagrophytes) but low density in Macaé (E. floccosum). Significant spatiotemporal clusters on dermatophytosis cases were detected in distinct municipalities (p-value ≤ 0.05). The Vulnerability Index (r = 0.293) and Demographic Density (r = 0.652) distributed according to neighborhoods in Niterói were direct related with dermatophytosis cases whereas Income (r = -0.306) was inversely correlated (p-value ≤ 0.05). The dermatophytosis spatiotemporal distinct distribution after two major international events in Rio de Janeiro, Brazil, highlight the pressing need for specific measures of its prevention and controlling. This is particularly relevant in touristic tropical localities which must consider both socio-economical and traveler's medicine variables.

Ethyl acetate fractions of Myrciaria floribunda, Ocotea pulchella, and Ocotea notata exhibit promising in vitro activity against Sporothrix brasiliensis isolates with low susceptibility to itraconazole.

Sporothrix brasiliensis with low susceptibility isolates were described from the Brazilian zoonotic sporotrichosis hyperendemics. The aim of this work was to evaluate distinct fractions of Ocotea pulchella, Ocotea notata, Myrciaria floribunda, and Hypericum brasiliense plant extracts against itraconazole-sensitive and low susceptibility S. brasiliensis isolates. Crude extracts were tested against clinical isolates and the ATCC MYA4823 to determine the minimum inhibitory concentrations (MICs) and fungicidal or fungistatic activities (MFC). A high MICs and MFCs amplitude (1 - > 128 µg/mL) were obtained for seven extracts. The highest antimicrobial activities against sensitive S. brasiliensis were displayed by the ethyl acetate extracts of O. notata (MIC = 2-128 µg/mL) and M. floribunda (MIC = 1-8 µg/mL). A fungicidal effect was observed for all fraction extracts. Ocotea spp. and M. floribunda ethyl acetate extracts provide promising profiles against itraconazole-sensitive or low susceptibility S. brasiliensis. Future studies will determine if these extracts can contribute as alternative therapies to this neglected zoonosis.

Sporothrix brasiliensis Infection Modulates Antimicrobial Peptides and Stress Management Gene Expression in the Invertebrate Biomodel Galleria mellonella.

Sporothrix brasiliensis is the most pathogenic species, responsible for the Brazilian cat-transmitted sporotrichosis hyperendemic. In this scenario, an investigation of the pathogen-host interaction can provide relevant information for future treatment strategies. To this end, the invertebrate Galleria mellonella has proven to be a suitable alternative for evaluating the virulence of pathogenic fungi, since the insect immune system is similar to the mammalian innate immune response. The aim of this work was to investigate phenotypic and molecular aspects of the immune response of G. mellonella throughout the S. brasiliensis infection. Hemocyte density and the evolution of the fungal load were evaluated. In parallel, RT-qPCR expression analysis of genes encoding antimicrobial peptides (Gallerimycin and Galiomycin) and stress management genes (C7 Contig 15362 and C8 Contig 19101) was conducted. The fungal load and hemocyte densities increased simultaneously and proportionally to the deleterious morphological events and larvae mortality. Gallerimycin, C7 Contig 15362 and C8 Contig 19101 genes were positively regulated (p < 0.05) at distinct moments of S. brasiliensis infection, characterizing a time-dependent and alternately modulated profile. Galiomycin gene expression remained unchanged. Our results contribute to the future proposal of potential alternative pathways for treating and consequently controlling S. brasiliensis zoonosis, a major public health issue in Latin America.

Population-based genomic study of Plasmodium vivax malaria in seven Brazilian states and across South America.

Background: Brazil is a unique and understudied setting for malaria, with complex foci of transmission associated with human and environmental conditions. An understanding of the population genomic diversity of P. vivax parasites across Brazil can support malaria control strategies. Methods: Through whole genome sequencing of P. vivax isolates across 7 Brazilian states, we use population genomic approaches to compare genetic diversity within country (n = 123), continent (6 countries, n = 315) and globally (26 countries, n = 885). Findings: We confirm that South American isolates are distinct, have more ancestral populations than the other global regions, with differentiating mutations in genes under selective pressure linked to antimalarial drugs (pvmdr1, pvdhfr-ts) and mosquito vectors (pvcrmp3, pvP45/48, pvP47). We demonstrate Brazil as a distinct parasite population, with signals of selection including ABC transporter (PvABCI3) and PHIST exported proteins. Interpretation: Brazil has a complex population structure, with evidence of P. simium infections and Amazonian parasites separating into multiple clusters. Overall, our work provides the first Brazil-wide analysis of P. vivax population structure and identifies important mutations, which can inform future research and control measures. Funding: AI is funded by an MRC LiD PhD studentship. TGC is funded by the Medical Research Council (Grant no. MR/M01360X/1, MR/N010469/1, MR/R025576/1, MR/R020973/1 and MR/X005895/1). SC is funded by Medical Research Council UK grants (MR/M01360X/1, MR/R025576/1, MR/R020973/1 and MR/X005895/1) and Bloomsbury SET (ref. CCF17-7779). FN is funded by The Shloklo Malaria Research Unit - part of the Mahidol Oxford Research Unit, supported by the Wellcome Trust (Grant no. 220211). ARSB is funded by São Paulo Research Foundation - FAPESP (Grant no. 2002/09546-1). RLDM is funded by Brazilian National Council for Scientific and Technological Development - CNPq (Grant no. 302353/2003-8 and 471605/2011-5); CRFM is funded by FAPESP (Grant no. 2020/06747-4) and CNPq (Grant no. 302917/2019-5 and 408636/2018-1); JGD is funded by FAPESP fellowships (2016/13465-0 and 2019/12068-5) and CNPq (Grant no. 409216/2018-6).

Association of toll-like receptors in malaria susceptibility and immunopathogenesis: A meta-analysis.

Toll-like receptors (TLRs) play a key role in the induced immune response in malaria. Although the potential roles of TLRs have been described, it is necessary to elucidate which of these receptors may actually have an impact on the immunopathogenesis of the disease. This article performed a meta-analysis adhered to the PRISMA statement on TLRs studied in malaria by Plasmodium falciparum and Plasmodium vivax and its impact on susceptibility and pathogenesis during malaria. A search of the literature was undertaken in PubMed, LILACS and SciELO published until June 30th, 2020. The risk of bias was calculated using the Joanna Briggs Institute's Critical Review Checklist. Later, based on the inclusion and/or exclusion criteria, 17 out of 296 articles were harvested for this systematic review, the meta-analysis included studies incorporating 6,747 cases and 8,983 controls. The results showed that only TLR1, TLR9 and TLR4 receptors were associated with parasitemia, TLR2 and TLR6 were related with severity and none TLR was correlated with susceptibility. The data described here should be taken with caution, since the current evidence is limited and inconsistent. More studies are needed given that the results may change depending on the region and genetic background of the populations.

Association between vitamin D serum levels and clinical, laboratory, and parasitological parameters in patients with malaria from an endemic area of the Amazon.

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.

Soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) and other inflammatory mediators in malaria by Plasmodium vivax during enteroparasites coinfection.

Malaria is a major health issue with more than 200 million cases occurring annually. Moreover, in Malaria endemic area are frequently observed Malaria-enteroparasite co-infections associated with the modulation of inflammatory response. In this aspect, biomarkers play an important role in the disease prognosis. This study aimed to evaluate inflammatory mediators in malaria during coinfection with enteroparasites. A subset of serum samples already collected was analyzed and divided into four groups: Malaria (n = 34), Co-infected (n = 116), Enteroparasite (n = 120) and Control (n = 95). The serum levels of sTREM-1 and IL-6 were measured by ELISA. TNF-α, and IL-10 levels were previously carried out by flow cytometry. Higher serum levels of sTREM-1 and IL-6 were showed in malaria patients compared to healthy controls. In co-infected malarial patients sTREM-1 serum levels were similar to control group. Interestingly, co-infected malaria patients showed IL-6 serum levels decreased compared to individuals only infected with P. vivax. However, in Malaria patients and co-infected there was a positive correlation between the IL-6 and IL-10 levels (P < 0.0001). This is the first report of sTREM-1 levels in P. vivax infected. Moreover, the results revealing a divergent effect of co-infection with the increased balance between pro-and anti-inflammatory cytokines and reduced IL-6 levels but increases the anemia occurrence. The results also highlight the potential use of IL-6 as a biomarker for P. vivax and enteroparasites coinfection.