RESUMO
In Brazil, malaria transmission is mostly confined to the Amazon, where substantial progress has been made towards disease control in the past decade. Vector control has been historically considered a fundamental part of the main malaria control programs implemented in Brazil. However, the conventional vector-control tools have been insufficient to control or eliminate local vector populations due to the complexity of the Amazonian rainforest environment and ecological features of malaria vector species in the Amazon, especially Anopheles darlingi. Malaria elimination in Brazil and worldwide eradication will require a combination of conventional and new approaches that takes into account the regional specificities of vector populations and malaria transmission dynamics. Here we present an overview on both conventional and novel promising vector-focused tools to curb malaria transmission in the Brazilian Amazon. If well designed and employed, vector-based approaches may improve the implementation of malaria-control programs, particularly in remote or difficult-to-access areas and in regions where existing interventions have been unable to eliminate disease transmission. However, much effort still has to be put into research expanding the knowledge of neotropical malaria vectors to set the steppingstones for the optimization of conventional and development of innovative vector-control tools.
RESUMO
BACKGROUND: The surface of infected red blood cells (iRBCs) has been widely investigated because of the molecular complexity and pathogenesis mechanisms involved. Asymptomatic individuals are important in the field because they can perpetuate transmission as natural reservoirs and present a challenge for diagnosing malaria because of their low levels of circulating parasites. Recent studies of iRBC antibody recognition have shown that responses are quantitatively similar in symptomatic and asymptomatic infections, but no studies have characterised the plasmodial proteins targeted by this response. OBJECTIVES: Our main objective was to identify Plasmodium falciparum proteins associated with iRBC ghosts recognised by antibodies in the sera of symptomatic and asymptomatic individuals in the Brazilian Amazon. METHODS: We collected symptomatic and asymptomatic sera from patients residing in the Brazilian Amazon and P. falciparum iRBC ghosts to identify the proteins involved in natural antibody recognition by 2D-electrophoresis, western blotting, and high- resolution mass spectrometry. FINDINGS: 2D gel-based immunoproteome analysis using symptomatic and asymptomatic sera identified 11 proteins with at least one unique peptide, such as chaperones HSP70-1 and HSP70-x, which likely are components of the secretion machinery/PTEX translocon. PfEMP1 is involved in antigenic variation in symptomatic infections and we found putative membrane proteins whose functions are unknown. MAIN FINDINGS: Our results suggest a potential role of old and new proteins, such as antigenic variation proteins, iRBC remodelling, and membrane proteins, with no assigned functions related to the immune response against P. falciparum, providing insights into the pathogenesis, erythrocyte remodelling, and secretion machinery important for alternative diagnosis and/or malaria therapy.
Assuntos
Anticorpos Antiprotozoários/genética , Antígenos de Protozoários/genética , Membrana Eritrocítica/parasitologia , Plasmodium falciparum/imunologia , Anticorpos Antiprotozoários/imunologia , Antígenos de Protozoários/imunologia , Infecções Assintomáticas , Western Blotting , Eletroforese em Gel Bidimensional , Membrana Eritrocítica/imunologia , Humanos , Espectrometria de Massas , Plasmodium falciparum/genética , ProteômicaRESUMO
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. In order to establish a link between cytoadherence, IRBC surface antibody recognition and the presence or absence of malaria symptoms, we phenotype-selected four Amazonian P. falciparum isolates and the laboratory strain 3D7 for their cytoadherence to CD36 and ICAM1 expressed on CHO cells. We then mapped the dominantly expressed var transcripts and tested whether antibodies from symptomatic or asymptomatic infections showed a differential recognition of the IRBC surface. As controls, the 3D7 lineages expressing severe disease-associated phenotypes were used. We showed that there was no profound difference between the frequency and intensity of antibody recognition of the IRBC-exposed P. falciparum proteins in symptomatic vs. asymptomatic infections. The 3D7 lineages, which expressed severe malaria-associated phenotypes, were strongly recognised by most, but not all plasmas, meaning that the recognition of these phenotypes is frequent in asymptomatic carriers, but is not necessarily a prerequisite to staying free of symptoms.
Assuntos
Anticorpos Antiprotozoários/imunologia , Antígenos CD36/imunologia , Eritrócitos/parasitologia , Malária Falciparum/imunologia , Plasmodium falciparum/imunologia , Proteínas de Protozoários/imunologia , Animais , Infecções Assintomáticas , Células CHO , Adesão Celular/genética , Adesão Celular/imunologia , Cricetulus , Eritrócitos/imunologia , Citometria de Fluxo , Perfilação da Expressão Gênica , Humanos , Malária Falciparum/parasitologia , Proteínas de Protozoários/genética , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
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. In order to establish a link between cytoadherence, IRBC surface antibody recognition and the presence or absence of malaria symptoms, we phenotype-selected four Amazonian P. falciparum isolates and the laboratory strain 3D7 for their cytoadherence to CD36 and ICAM1 expressed on CHO cells. We then mapped the dominantly expressed var transcripts and tested whether antibodies from symptomatic or asymptomatic infections showed a differential recognition of the IRBC surface. As controls, the 3D7 lineages expressing severe disease-associated phenotypes were used. We showed that there was no profound difference between the frequency and intensity of antibody recognition of the IRBC-exposed P. falciparum proteins in symptomatic vs. asymptomatic infections. The 3D7 lineages, which expressed severe malaria-associated phenotypes, were strongly recognised by most, but not all plasmas, meaning that the recognition of these phenotypes is frequent in asymptomatic carriers, but is not necessarily a prerequisite to staying free of symptoms. .