Exploring the naturally acquired response to Pvs47 gametocyte antigen.

Malaria represents a challenging global public health task, with being the predominant parasite in Brazil and the most widely distributed species throughout the world. Developing a vaccine against malaria demands innovative strategies, and targeting gametocyte antigens shows promise for blocking transmission prevention. Among these antigens, Pvs47, expressed in gametocytes, has shown remarkable efficacy in transmission blocking.

Perception and barriers to access Pre-exposure Prophylaxis for HIV/AIDS (PrEP) among the MSM (men who have sex with men) Brazilian Amazon: A qualitative study.

Pre-exposure prophylaxis (PrEP) is an effective HIV prevention strategy that consists in the use of antiretroviral drugs by seronegative people at risk of HIV. Negative perceptions, inadequate understanding, and access barriers have been associated with decreased medication adherence. Manaus is the largest city in the Brazilian Amazon, where the incidence of HIV/AIDS is high, and the rates of adherence to the antiretroviral treatment for HIV and PrEP are low.

Cell Death of Blood Stages Occurs in Absence of Classical Apoptotic Events and Induces Eryptosis of Parasitized Host Cells.

Elucidation of pathways regulating parasite cell death is believed to contribute to identification of novel therapeutic targets for protozoan diseases, and in this context, apoptosis-like cell death has been reported in different groups of protozoa, in which metacaspases seem to play a role. In the genus , apoptotic markers have been detected in and , and no study focusing on cell death has been reported so far. In the present study, we investigated the susceptibility of to undergo apoptotic cell death after incubating mature trophozoites with the classical apoptosis inducer staurosporine.

Profile of metacaspase gene expression in Plasmodium vivax field isolates from the Brazilian Amazon.

Background: Metacaspases comprise a family of cysteine proteases implicated in both cell death and cell differentiation of protists that has been considered a potential drug target for protozoan parasites. However, the biology of metacaspases in Plasmodium vivax - the second most prevalent and most widespread human malaria parasite worldwide, whose occurrence of chemoresistance has been reported in many endemic countries, remains largely unexplored. Therefore, the present study aimed to address, for the first time, the expression pattern of metacaspases in P.

Evolution and assembly of 's immune genes: primary malaria vector of coastal Central and South America and the Caribbean Islands.

Anophelines are vectors of malaria, the deadliest disease worldwide transmitted by mosquitoes. The availability of genomic data from various species allowed evolutionary comparisons of the immune response genes in search of alternative vector control of the malarial parasites. Now, with the genome, it was possible to obtain more information about the evolution of the immune response genes.

The activity of methylene blue against asexual and sexual stages of .

Methylene blue (MB) is an alternative for combating drug-resistant malaria parasites. Its transmission-blocking potential has been demonstrated in murine models, , and in clinical trials. MB shows high efficacy against asexual stages; however, its efficacy in sexual stages is unknown.

Rosette formation by gametocytes favors the infection in .

a public health problem and the most common type of malaria outside sub-Saharan Africa. The capacity of cytoadhesion, rosetting, and liver latent phase development could impact treatment and disease control. Although the ability to gametocyte develop rosetting is known, it is not yet clear which role it plays during the infection and transmission process to the mosquito.

Gametocytes Adherence to Bone Marrow Endothelial Cells.

In a infection, it was shown a proportionally increased on gametocyte distribution within the bone marrow aspirant, suggesting a role of this organ as a reservoir for this parasite stage. Here, we evaluated the cytoadhesive capacity of gametocytes to bone marrow endothelial cells (HBMEC) and investigated the involvement of some receptors in the cytoadhesion process by using transfected CHO cells (CHO-ICAM1, CHO-CD36 and CHO-VCAM), wild type (CHO-K1) or deficient in heparan and chondroitin sulfate (CHO-745). cytoadhesion assays were performed using a total of 44  isolates enriched in gametocyte stages by Percoll gradient in the different cell lines.

Viability and Infectivity of Gametocytes in Short-Term Culture.

The control and elimination of malaria caused by both represent a great challenge due to the biological aspects of the species. Gametocytes are the forms responsible for the transmission of the parasite to the vector and the search for new strategies for blocking transmission are essential in a scenario of control and elimination The challenges in this search in regard to mainly stem from the lack of a long-term culture and the limitation of studies of gametocytes. This study evaluated the viability and infectivity of gametocytes in short-term culture.

Violacein-Induced Chaperone System Collapse Underlies Multistage Antiplasmodial Activity.

Antimalarial drugs with novel modes of action and wide therapeutic potential are needed to pave the way for malaria eradication. Violacein is a natural compound known for its biological activity against cancer cells and several pathogens, including the malaria parasite, (Pf). Herein, using chemical genomic profiling (CGP), we found that violacein affects protein homeostasis.

Transmission-blocking compound candidates against Plasmodium vivax using P. berghei as an initial screening.

Background: Different strategies for improvement of malaria control and elimination are based on the blockage of malaria parasite transmission to the mosquito vector. These strategies include the drugs that target the plasmodial sexual stages in humans and the early developmental stages inside mosquitoes.

Objectives: Here we tested Malaria Box compounds in order to evaluate their activity against male and female gametocytes in Plasmodium berghei, mosquito infection in P.

Platelet disturbances correlate with endothelial cell activation in uncomplicated Plasmodium vivax malaria.

Platelets drive endothelial cell activation in many diseases. However, if this occurs in Plasmodium vivax malaria is unclear. As platelets have been reported to be activated and to play a role in inflammatory response during malaria, we hypothesized that this would correlate with endothelial alterations during acute illness.

A First Natural Infection Induces Increased Activity of the Interferon Gamma-Driven Tryptophan Catabolism Pathway.

The human immune response that controls infection in the liver and blood stages of the parasite life cycle is composed by both pro- and anti-inflammatory programs. Pro-inflammatory responses primarily mediated by IFN-γ controls the infection, but also induce tolerogenic mechanisms to limit host damage, including the tryptophan (TRP) catabolism pathway mediated by the enzyme Indoleamine 2,3-Dioxygenase (IDO1), an enzyme that catalyzes the degradation of TRP to kynurenines (KYN). Here we assessed total serum kynurenines and cytokine dynamics in a cohort of natural human infection and compared them to those of endemic healthy controls and other febrile diseases.

A simple, ex vivo phagocytosis assay of Plasmodium vivax merozoites by flow cytometry.

As phagocytosis is the first line of defense against malaria, we developed a phagocytosis assay with Plasmodium vivax (P. vivax) merozoites that can be applied to evaluate vaccine candidates. Briefly, after leukocyte removal with loosely packed cellulose powder in a syringe, P.

Chloroquine resistance is associated to multi-copy pvcrt-o gene in Plasmodium vivax malaria in the Brazilian Amazon.

Background: The resistance of Plasmodium vivax to chloroquine has become an obstacle to control strategies based on the use of anti-malarials. The current study investigated the association between P. vivax CQ-resistance in vivo with copy number variation and mutations in the promoter region in pvcrt-o and pvmdr1 genes.

The role of the peritrophic matrix and red blood cell concentration in Plasmodium vivax infection of Anopheles aquasalis.

Background: Plasmodium vivax is predominant in the Amazon region, and enhanced knowledge of its development inside a natural vector, Anopheles aquasalis, is critical for future strategies aimed at blocking parasite development. The peritrophic matrix (PM), a chitinous layer produced by the mosquito midgut in response to blood ingestion, is a protective barrier against pathogens. Plasmodium can only complete its life-cycle, and consequently be transmitted to a new host, after successfully passing this barrier.

Violacein Treatment Modulates Acute and Chronic Inflammation through the Suppression of Cytokine Production and Induction of Regulatory T Cells.

Inflammation is a necessary process to control infection. However, exacerbated inflammation, acute or chronic, promotes deleterious effects in the organism. Violacein (viola), a quorum sensing metabolite from the Gram-negative bacterium Chromobacterium violaceum, has been shown to protect mice from malaria and to have beneficial effects on tumors.

Exacerbation of autoimmune neuro-inflammation in mice cured from blood-stage Plasmodium berghei infection.

The thymus plays an important role shaping the T cell repertoire in the periphery, partly, through the elimination of inflammatory auto-reactive cells. It has been shown that, during Plasmodium berghei infection, the thymus is rendered atrophic by the premature egress of CD4+CD8+ double-positive (DP) T cells to the periphery. To investigate whether autoimmune diseases are affected after Plasmodium berghei NK65 infection, we immunized C57BL/6 mice, which was previously infected with P.

Antibody recognition of Plasmodium falciparum infected red blood cells by symptomatic and asymptomatic individuals in the Brazilian Amazon.

In the Amazon Region, there is a virtual absence of severe malaria and few fatal cases of naturally occurring Plasmodium falciparum infections; this presents an intriguing and underexplored area of research. In addition to the rapid access of infected persons to effective treatment, one cause of this phenomenon might be the recognition of cytoadherent variant proteins on the infected red blood cell (IRBC) surface, including the var gene encoded P. falciparum erythrocyte membrane protein 1.

Amazonian plant natural products: perspectives for discovery of new antimalarial drug leads.

Plasmodium falciparum and P. vivax malaria parasites are now resistant, or showing signs of resistance, to most drugs used in therapy. Novel chemical entities that exhibit new mechanisms of antiplasmodial action are needed.

Chloroquine: modes of action of an undervalued drug.

For more than two decades, chloroquine (CQ) was largely and deliberately used as first choice drug for malaria treatment. However, worldwide increasing cases of resistant strains of Plasmodium have hampered its use. Nevertheless, CQ has recently been tested as adjunct therapy in several inflammatory situations, such as rheumatoid arthritis and transplantation procedures, presenting intriguing and promising results.