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.

Dynamics of IgM and IgG Antibody Response Profile against Linear B-Cell Epitopes from Exoerythrocytic (CelTOS and TRAP) and Erythrocytic (CyRPA) Phases of : Follow-Up Study.

Malaria is a serious health problem worldwide affecting mainly children and socially vulnerable people. The biological particularities of , such as the ability to generate dormant liver stages, the rapid maturation of gametocytes, and the emergence of drug resistance, have contributed to difficulties in disease control. In this context, developing an effective vaccine has been considered a fundamental tool for the efficient control and/or elimination of vivax malaria.

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.

Are and Gene Mutations Associated with Chloroquine-Resistant Parasites?

(1) Background: Malaria remains a significant global public health issue. Since parasites quickly became resistant to most of the available antimalarial drugs, treatment effectiveness must be constantly monitored. In Brazil, up to 10% of cases of vivax malaria resistant to chloroquine (CQ) have been registered.

IgM antibody responses against antigens in neotropical primates in the Brazilian Atlantic Forest.

Introduction: Zoonotic transmission is a challenge for the control and elimination of malaria. It has been recorded in the Atlantic Forest, outside the Amazon which is the endemic region in Brazil. However, only very few studies have assessed the antibody response, especially of IgM antibodies, in Neotropical primates (NP).

Construction, Expression, and Evaluation of the Naturally Acquired Humoral Immune Response against RMC-1, a Multistage Chimeric Protein.

The PvCelTOS, PvCyRPA, and Pvs25 proteins play important roles during the three stages of the lifecycle. In this study, we designed and expressed a recombinant modular chimeric protein (PvRMC-1) composed of the main antigenic regions of these vaccine candidates. After structure modelling by prediction, the chimeric protein was expressed, and the antigenicity was assessed by IgM and IgG (total and subclass) ELISA in 301 naturally exposed individuals from the Brazilian Amazon.

Chloroquine- Resistant Haplotypes in Brazilian Endemic Areas Four Decades after CQ Withdrawn.

(1) Background: Malaria is a public health problem worldwide. Despite global efforts to control it, antimalarial drug resistance remains a great challenge. In 2009, our team identified, for the first time in Brazil, chloroquine (CQ)-susceptible parasites in isolates from the Brazilian Amazon.

B-Cell Epitope Mapping of the Malaria Vaccine Candidate GMZ2.6c in a Naturally Exposed Population of the Brazilian Amazon.

The GMZ2.6c malaria vaccine candidate is a multi-stage chimeric protein that contains a fragment of the sexual-stage s48/45-6C protein genetically fused to GMZ2, an asexual-stage vaccine construction consisting of the N-terminal region of the glutamate-rich protein (GLURP) and the C-terminal region of the merozoite surface protein-3 (MSP-3). Previous studies showed that GMZ2.

Modulation of Signal Regulatory Protein α (SIRPα) by Antigenic Extract: A Preliminary In Vitro Study on Peripheral Blood Mononuclear Cells.

Signal regulatory protein α (SIRPα) is an immunoreceptor expressed in myeloid innate immune cells that signals for inhibition of both phagocytosis and inflammatory response. Malaria parasites have evolutionarily selected multiple mechanisms that allow them to evade host immune defenses, including the modulation of cells belonging to innate immunity. Notwithstanding, little attention has been given to SIRPα in the context of immunosuppressive states induced by malaria.

Naturally acquired antibody response to a Plasmodium falciparum chimeric vaccine candidate GMZ2.6c and its components (MSP-3, GLURP, and Pfs48/45) in individuals living in Brazilian malaria-endemic areas.

Background: The GMZ2.6c malaria vaccine candidate is a multi-stage Plasmodium falciparum chimeric protein which contains a fragment of the sexual-stage Pfs48/45-6C protein genetically fused to GMZ2, a fusion protein of GLURP and MSP-3, that has been shown to be well tolerated, safe and immunogenic in clinical trials performed in a malaria-endemic area of Africa. However, there is no data available on the antigenicity or immunogenicity of GMZ2.

2D6 Allele Frequency in Five Malaria Vivax Endemic Areas From Brazilian Amazon Region.

Genetic variability was linked with individual responses to treatment and susceptibility to malaria by . Polymorphisms in the 2D6 gene may modulate enzyme level and activity, thereby affecting individual responses to pharmacological treatment. The aim of the study was to investigate whether or not 2D6 single nucleotide polymorphisms rs1065852, rs38920-97, rs16947 and rs28371725 are unequally distributed in malaria by individuals from the Brazilian Amazon region.

Recombinant Plasmodium vivax circumsporozoite surface protein allelic variants: antibody recognition by individuals from three communities in the Brazilian Amazon.

Circumsporozoite protein (CSP) variants of P. vivax, besides having variations in the protein repetitive portion, can differ from each other in aspects such as geographical distribution, intensity of transmission, vectorial competence and immune response. Such aspects must be considered to P.

Polymorphism in the IL-1β promoter is associated with IgG antibody response to circumsporozoite protein repeats of Plasmodium vivax.

Background: It is well established that infection by Plasmodium vivax is a result of host-parasite interactions. In the present study, association with the IL1/IL2 cytokine profiles, anticircumsporozoite protein antibody levels and parasitic loads was evaluated in individuals naturally infected with P. vivax in an endemic area of the Brazilian Amazon.

Antibody Responses Against TRAP Recombinant and Synthetic Antigens in Naturally Exposed Individuals From the Brazilian Amazon.

Thrombospondin-related adhesive protein (TRAP) is essential for sporozoite motility and the invasion of mosquitoes' salivary gland and vertebrate's hepatocyte and is, thus, considered a promising pre-erythrocytic vaccine candidate. Despite the existence of a few reports on naturally acquired immune response against TRAP (PvTRAP), it has never been explored so far in the Amazon region, so results are conflicting. Here, we characterized the (IgG and IgG subclass) antibody reactivity against recombinant PvTRAP in a cross-sectional study of 299 individuals exposed to malaria infection in three municipalities (Cruzeiro do Sul, Mâncio Lima and Guajará) from the Acre state of the Brazilian Amazon.

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.

Plasmodium vivax ookinete surface protein (Pvs25) is highly conserved among field isolates from five different regions of the Brazilian Amazon.

The Plasmodium vivax Ookinete Surface Protein (Pvs25) is one of the leading malaria Transmission-Blocking Vaccine candidates based on its high immunogenicity in animal models, transmission-blocking activity of antibodies elicited in clinical trials and high conservation among P. vivax isolates from endemic areas. However, the polymorphism in gene encoding Pvs25 in endemic areas from South America has been poorly studied so far.

Clinical and immunological profiles of anaemia in children and adolescents with Plasmodium vivax malaria in the Pará state, Brazilian Amazon.

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.

Detection of Signal Regulatory Protein α in (Squirrel Monkey) by Anti-Human Monoclonal Antibody.

Non-human primates (NHP) are suitable models for studying different aspects of the human system, including pathogenesis and protective immunity to many diseases. However, the lack of specific immunological reagents for neo-tropical monkeys, such as , is still a major factor limiting studies in these models. An alternative strategy to circumvent this obstacle has been the selection of immunological reagents directed to humans, which present cross-reactivity with NHP molecules.

Synthetic Antigens Derived from Sporozoite, Liver, and Blood Stages: Naturally Acquired Immune Response and Human Leukocyte Antigen Associations in Individuals Living in a Brazilian Endemic Area.

Peptide vaccine strategies using -derived antigens have emerged as an attractive approach against malaria. However, relatively few studies have been conducted with malaria-exposed populations from non-African countries. Herein, the seroepidemiological profile against of naturally exposed individuals from a Brazilian malaria-endemic area against synthetic peptides derived from vaccine candidates circumsporozoite protein (CSP), liver stage antigen-1 (LSA-1), erythrocyte binding antigen-175 (EBA-175), and merozoite surface protein-3 (MSP-3) was investigated.