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1.
PLoS Negl Trop Dis ; 14(7): e0008471, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32639964

RESUMO

In Brazil, Plasmodium vivax infection accounts for around 80% of malaria cases. This infection has a substantial impact on the productivity of the local population as the course of the disease is usually prolonged and the development of acquired immunity in endemic areas takes several years. The recent emergence of drug-resistant strains has intensified research on alternative control methods such as vaccines. There is currently no effective available vaccine against malaria; however, numerous candidates have been studied in the past several years. One of the leading candidates is apical membrane antigen 1 (AMA1). This protein is involved in the invasion of Apicomplexa parasites into host cells, participating in the formation of a moving junction. Understanding how the genetic diversity of an antigen influences the immune response is highly important for vaccine development. In this study, we analyzed the diversity of AMA1 from Brazilian P. vivax isolates and 19 haplotypes of P. vivax were found. Among those sequences, 33 nonsynonymous PvAMA1 amino acid sites were identified, whereas 20 of these sites were determined to be located in predicted B-cell epitopes. Nonsynonymous mutations were evaluated for their influence on the immune recognition of these antigens. Two distinct haplotypes, 5 and 16, were expressed and evaluated for reactivity in individuals from northern Brazil. Both PvAMA1 variants were reactive. Moreover, the IgG antibody response to these two PvAMA1 variants was analyzed in an exposed but noninfected population from a P. vivax endemic area. Interestingly, over 40% of this population had antibodies recognizing both variants. These results have implications for the design of a vaccine based on a polymorphic antigen.


Assuntos
Antígenos de Protozoários/genética , Malária Vivax/imunologia , Malária Vivax/parasitologia , Proteínas de Membrana/genética , Plasmodium vivax/genética , Proteínas de Protozoários/genética , Dicroísmo Circular , DNA de Protozoário/genética , Epitopos de Linfócito B , Haplótipos , Humanos , Malária Vivax/epidemiologia , Mutação , Plasmodium vivax/imunologia , Conformação Proteica , Proteínas Recombinantes
2.
Malar J ; 17(1): 401, 2018 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-30382855

RESUMO

BACKGROUND: The genetic diversity of malaria antigens often results in allele variant-specific immunity, imposing a great challenge to vaccine development. Rhoptry Neck Protein 2 (PvRON2) is a blood-stage antigen that plays a key role during the erythrocyte invasion of Plasmodium vivax. This study investigates the genetic diversity of PvRON2 and the naturally acquired immune response to P. vivax isolates. RESULTS: Here, the genetic diversity of PvRON21828-2080 and the naturally acquired humoral immune response against PvRON21828-2080 in infected and non-infected individuals from a vivax malaria endemic area in Brazil was reported. The diversity analysis of PvRON21828-2080 revealed that the protein is conserved in isolates in Brazil and worldwide. A total of 18 (19%) patients had IgG antibodies to PvRON21828-2080. Additionally, the analysis of the antibody response in individuals who were not acutely infected with malaria, but had been infected with malaria in the past indicated that 32 patients (33%) exhibited an IgG immune response against PvRON2. CONCLUSIONS: PvRON2 was conserved among the studied isolates. The presence of naturally acquired antibodies to this protein in the absence of the disease suggests that PvRON2 induces a long-term antibody response. These results indicate that PvRON2 is a potential malaria vaccine candidate.


Assuntos
Variação Genética , Imunidade Humoral , Malária Vivax/imunologia , Plasmodium vivax/genética , Proteínas de Protozoários/genética , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas de Protozoários/imunologia , Análise de Sequência de DNA
3.
Vaccine ; 35(18): 2463-2472, 2017 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-28341111

RESUMO

Plasmodium vivax is the most widely distributed malaria species and the most prevalent species of malaria in America and Asia. Vaccine development against P. vivax is considered a priority in the global program for the eradication of malaria. Earlier studies have characterized the Apical Membrane Antigen 1 (AMA-1) ectodomain and the C-terminal region (19kDa) of the Merozoite Surface Protein 1 (MSP-1) of P. vivax as immunodominant antigens. Based on this characterization, we designed a chimeric recombinant protein containing both merozoite immunodominant domains (PvAMA166-MSP119). The recombinant PvAMA166-MSP119 was successfully expressed in Pichia pastoris and used to immunize two different mouse strains (BALB/c and C57BL/6) in the presence of the Poly (I:C) as an adjuvant. Immunization with the chimeric protein induced high antibody titers against both proteins in both strains of mice as detected by ELISA. Antisera also recognized the native proteins expressed on the merozoites of mature P. vivax schizonts. Moreover, this antigen was able to induce IFN-gamma-secreting cells in C57BL/6 mice. These findings indicate that this novel yeast recombinant protein containing PvAMA166 and PvMSP119 is advantageous, because of improved antibody titers and cellular immune response. Therefore, this formulation should be further developed for pre-clinical trials in non-human primates as a potential candidate for a P. vivax vaccine.


Assuntos
Antígenos de Protozoários/imunologia , Vacinas Antimaláricas/imunologia , Proteínas de Membrana/imunologia , Proteína 1 de Superfície de Merozoito/imunologia , Plasmodium vivax/imunologia , Proteínas de Protozoários/imunologia , Proteínas Recombinantes de Fusão/imunologia , Adjuvantes Imunológicos/administração & dosagem , Animais , Anticorpos Antiprotozoários/sangue , Antígenos de Protozoários/genética , Ensaio de Imunoadsorção Enzimática , Feminino , Expressão Gênica , Interferon gama/metabolismo , Leucócitos Mononucleares/imunologia , Vacinas Antimaláricas/administração & dosagem , Vacinas Antimaláricas/genética , Proteínas de Membrana/genética , Proteína 1 de Superfície de Merozoito/genética , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Pichia/genética , Poli I-C/administração & dosagem , Proteínas de Protozoários/genética , Proteínas Recombinantes de Fusão/genética , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/genética , Vacinas Sintéticas/imunologia
4.
Malar J ; 15: 306, 2016 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-27255376

RESUMO

BACKGROUND: Humoral immune responses against proteins of asexual blood-stage malaria parasites have been associated with clinical immunity. However, variations in the antibody-driven responses may be associated with a genetic component of the human host. The objective of the present study was to evaluate the influence of co-stimulatory molecule gene polymorphisms of the immune system on the magnitude of the humoral immune response against a Plasmodium vivax vaccine candidate antigen. METHODS: Polymorphisms in the CD28, CTLA4, ICOS, CD40, CD86 and BLYS genes of 178 subjects infected with P. vivax in an endemic area of the Brazilian Amazon were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The levels of IgM, total IgG and IgG subclasses specific for ICB2-5, i.e., the N-terminal portion of P. vivax merozoite surface protein 1 (PvMSP-1), were determined by enzyme-linked immuno assay. The associations between the polymorphisms and the antibody response were assessed by means of logistic regression models. RESULTS: After correcting for multiple testing, the IgG1 levels were significantly higher in individuals recessive for the single nucleotide polymorphism rs3116496 in CD28 (p = 0.00004). Furthermore, the interaction between CD28 rs35593994 and BLYS rs9514828 had an influence on the IgM levels (p = 0.0009). CONCLUSIONS: The results of the present study support the hypothesis that polymorphisms in the genes of co-stimulatory components of the immune system can contribute to a natural antibody-driven response against P. vivax antigens.


Assuntos
Antígenos de Protozoários/imunologia , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Fatores Imunológicos/genética , Proteína 1 de Superfície de Merozoito/imunologia , Plasmodium vivax/imunologia , Polimorfismo Genético , Adolescente , Adulto , Idoso , Anticorpos Antiprotozoários/sangue , Brasil , Estudos Transversais , Feminino , Técnicas de Genotipagem , Humanos , Imunogenética , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Adulto Jovem
5.
PLoS One ; 11(2): e0149581, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26901523

RESUMO

The development of an effective immune response can help decrease mortality from malaria and its clinical symptoms. However, this mechanism is complex and has significant inter-individual variation, most likely owing to the genetic contribution of the human host. Therefore, this study aimed to investigate the influence of polymorphisms in genes involved in the costimulation of B-lymphocytes in the naturally acquired humoral immune response against proteins of the asexual stage of Plasmodium vivax. A total of 319 individuals living in an area of malaria transmission in the Brazilian Amazon were genotyped for four SNPs in the genes CD40, CD40L, BLYS and CD86. In addition, IgG antibodies against P. vivax apical membrane antigen 1 (PvAMA-1), Duffy binding protein (PvDBP) and merozoite surface protein 1 (PvMSP-119) were detected by ELISA. The SNP BLYS -871C>T was associated with the frequency of IgG responders to PvAMA-1 and PvMSP-119. The SNP CD40 -1C>T was associated with the IgG response against PvDBP, whereas IgG antibody titers against PvMSP-119 were influenced by the polymorphism CD86 +1057G>A. These data may help to elucidate the immunological aspects of vivax malaria and consequently assist in the design of malaria vaccines.


Assuntos
Anticorpos Antiprotozoários/imunologia , Antígenos CD , Imunoglobulina G/imunologia , Malária Vivax , Plasmodium vivax/imunologia , Polimorfismo de Nucleotídeo Único/imunologia , Proteínas de Protozoários/imunologia , Adolescente , Adulto , Idoso , Antígenos CD/genética , Antígenos CD/imunologia , Feminino , Humanos , Malária Vivax/genética , Malária Vivax/imunologia , Masculino , Pessoa de Meia-Idade
6.
Malar J ; 14: 402, 2015 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-26453152

RESUMO

BACKGROUND: Plasmodium vivax malaria is an important public health issue in the Amazon region, and it accounts for approximately 84 % of cases of the disease. Migration across the border between Brazil and French Guiana contributes to the maintenance of the disease. The aim of this study was to evaluate the therapeutic and parasitological responses of patients with P. vivax malaria treated with chloroquine and primaquine in the socio-environmental context of cross-border interactions between Brazil and French Guiana. The factors controlled were diagnostic agreement, adherence, adjustment of primaquine doses for patient weight, and quality of the drugs used. METHODS: A prospective study was conducted in 2011 with 103 individuals aged 10-60 years with a positive diagnosis of P. vivax treated with chloroquine (10 mg base/kg on the first day, followed by 7.5 mg/kg on the second and third days) and primaquine for 7 days, who were followed for 28 days. The primaquine doses were adjusted for the patients' weight. A number of factors were determined: epidemiological characteristics, origin of patients, signs and symptoms, initial parasitaemia and parasitaemia clearance time, blood concentrations of chloroquine and primaquine, quality of anti-malarial drugs and diagnostic agreement. RESULTS: Ninety-five patients were followed for 28 days. There was a 100 % agreement in microscopic diagnosis between field laboratory and reference centre. The adhesion to the treatment was 100 %. Of these patients, 32.6 % received a weight-adjusted dose of primaquine. The chloroquine and primaquine tablets were consistent with the optimal quality limits for human consumption. The investigated patients achieved optimal blood exposure to anti-malarial drugs. The parasitological and therapeutic response was adequate in 99.0 % of cases. CONCLUSIONS: In the municipality of Oiapoque, the therapeutic regime used for the treatment of P. vivax malaria using chloroquine combined with primaquine remains effective, when external factors are controlled, such as the quality of anti-malarial drugs, the adhesion to the treatment prescribed, the correct diagnostic and the adjustment of primaquine dose for patient body weight.


Assuntos
Antimaláricos/administração & dosagem , Malária Vivax/tratamento farmacológico , Adolescente , Adulto , Brasil/epidemiologia , Criança , Cloroquina/administração & dosagem , Quimioterapia Combinada/métodos , Feminino , Guiana Francesa , Migração Humana , Humanos , Malária Vivax/epidemiologia , Malária Vivax/parasitologia , Masculino , Pessoa de Meia-Idade , Primaquina/administração & dosagem , Estudos Prospectivos , Resultado do Tratamento , Adulto Jovem
7.
Trans R Soc Trop Med Hyg ; 107(6): 377-83, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23604864

RESUMO

BACKGROUND: Plasmodium vivax is the most prevalent malaria species in Brazil. The parasite-host coevolutionary process can be viewed as an 'arms race', in which adaptive genetic changes in one are eventually matched by alterations in the other. METHODS: Following the candidate gene approach we analyzed the CD40, CD40L and BLYS genes that participate in B-cell co-stimulation, for associations with P. vivax malaria. The study sample included 97 patients and 103 controls. We extracted DNA using the extraction and purification commercial kit and identified the following SNPs: -1C > T in the CD40 gene, -726T > C in the CD40L gene and the -871C > T in the BLyS gene using PCR-RFLP. We analyzed the genotype and allele frequencies by direct counting. We also compared the observed with the expected genotype frequencies using the Hardy-Weinberg equilibrium. RESULTS: The allele and genotype frequencies for these SNPs did not differ statistically between patient and control groups. Gene-gene interactions were not observed between the CD40 and BLYS and between the CD40L and BLYS genes. Overall, the genes were in Hardy-Weinberg equilibrium. Significant differences were not observed among the frequencies of antibody responses against P. vivax sporozoite and erythrocytic antigens and the CD40 and BLYS genotypes. CONCLUSIONS: The results of this study show that, although the investigated CD40, CD40L and BLYS alleles differ functionally, this variation does not alter the functionality of the molecules in a way that would interfere in susceptibility to the disease. The variants of these genes may influence the clinical course rather than simply increase or decrease susceptibility.


Assuntos
Fator Ativador de Células B/genética , Antígenos CD40/genética , Ligante de CD40/genética , Malária Vivax/genética , Plasmodium vivax/genética , Polimorfismo de Nucleotídeo Único , Adulto , Alelos , Antígenos de Protozoários/genética , Brasil , DNA de Protozoário/análise , Progressão da Doença , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Modelos Logísticos , Malária Vivax/imunologia , Masculino , Adulto Jovem
8.
PLoS One ; 7(10): e47913, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23118907

RESUMO

Studies of Plasmodium falciparum invasion pathways in field isolates have been limited. Red blood cell (RBC) invasion is a complex process involving two invasion protein families; Erythrocyte Binding-Like (EBL) and the Reticulocyte Binding-Like (PfRh) proteins, which are polymorphic and not fully characterized in field isolates. To determine the various P. falciparum invasion pathways used by parasite isolates from South America, we studied the invasion phenotypes in three regions: Colombia, Peru and Brazil. Additionally, polymorphisms in three members of the EBL (EBA-181, EBA-175 and EBL-1) and five members of the PfRh (PfRh1, PfRh2a, PfRh2b, PfRh4, PfRh5) families were determined. We found that most P. falciparum field isolates from Colombia and Peru invade RBCs through an atypical invasion pathway phenotypically characterized as resistant to all enzyme treatments (NrTrCr). Moreover, the invasion pathways and the ligand polymorphisms differed substantially among the Colombian and Brazilian isolates while the Peruvian isolates represent an amalgam of those present in the Colombian and Brazilian field isolates. The NrTrCr invasion profile was associated with the presence of the PfRh2a pepC variant, the PfRh5 variant 1 and EBA-181 RVNKN variant. The ebl and Pfrh expression levels in a field isolate displaying the NrTrCr profile also pointed to PfRh2a, PfRh5 and EBA-181 as being possibly the major players in this invasion pathway. Notably, our studies demonstrate the uniqueness of the Peruvian P. falciparum field isolates in terms of their invasion profiles and ligand polymorphisms, and present a unique opportunity for studying the ability of P. falciparum parasites to expand their invasion repertoire after being reintroduced to human populations. The present study is directly relevant to asexual blood stage vaccine design focused on invasion pathway proteins, suggesting that regional invasion variants and global geographical variation are likely to preclude a simple one size fits all type of vaccine.


Assuntos
Eritrócitos , Malária Falciparum , Plasmodium falciparum , Proteínas de Protozoários , Animais , Eritrócitos/citologia , Eritrócitos/imunologia , Eritrócitos/parasitologia , Humanos , Ligantes , Vacinas Antimaláricas/imunologia , Malária Falciparum/genética , Malária Falciparum/imunologia , Malária Falciparum/metabolismo , Malária Falciparum/parasitologia , Fenótipo , Plasmodium falciparum/genética , Plasmodium falciparum/imunologia , Plasmodium falciparum/patogenicidade , Polimorfismo Genético , Proteínas de Protozoários/genética , Proteínas de Protozoários/imunologia , Proteínas de Protozoários/metabolismo , Reticulócitos/metabolismo , Reticulócitos/parasitologia , América do Sul
9.
Infect Genet Evol ; 12(3): 597-600, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22326538

RESUMO

UNLABELLED: Leprosy, a chronic infectious disease caused by Mycobacterium leprae, can damage the peripheral nervous system and represents one of the leading causes of nontraumatic neuropathy in some developing countries. The NINJURIN1 is a cell adhesion molecule that provides suitable substrates for repair of Schwann cells after peripheral nerve injury. The single nucleotide polymorphism NINJ1, is the result of a transversion of an adenine to a nucleotide polymorphic cytokine (A→C), responsible for an amino acid exchange of asparagine to alanine at position 110 of the protein (asp110ala). OBJECTIVES: The aim of this study was to investigate the importance of the polymorphism in the NINJ1 gene for neural impairment during leprosy course. METHODS: A single nucleotide polymorphism (asp110ala) was searched in 218 leprosy patients and 244 non-leprosy subjects using a polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: No statistical differences were observed in the frequency of the asp110ala SNP between leprosy patients versus non-leprosy and multibacillary versus paucibacillary clinical forms. The C allele (ala110) is increased among patients exhibiting nerve impairment (p=0.0379). Also, leprosy patients with the CC genotype (ala/ala) had a higher risk (OR=4.21) of developing nerve disability when compared those carrying the AA genotype (asp/asp) (OR=0.69). CONCLUSION: Our results show an association between the studied C allele (ala110) and damage nerve in leprosy patients. SIGNIFICANCE: Ninjurin analysis showed that asp110ala could be a valuable prognostic marker, since C allele (ala110) have increased susceptibility to nerve damage.


Assuntos
Moléculas de Adesão Celular Neuronais/genética , Hanseníase/patologia , Degeneração Neural/genética , Fatores de Crescimento Neural/genética , Polimorfismo de Nucleotídeo Único , Adenina/metabolismo , Adulto , Idoso , Alanina/genética , Alanina/metabolismo , Alelos , Asparagina/genética , Asparagina/metabolismo , Estudos de Casos e Controles , Moléculas de Adesão Celular Neuronais/metabolismo , Feminino , Genótipo , Humanos , Hanseníase/genética , Hanseníase/microbiologia , Masculino , Pessoa de Meia-Idade , Mycobacterium leprae/patogenicidade , Degeneração Neural/microbiologia , Degeneração Neural/patologia , Fatores de Crescimento Neural/metabolismo , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Fatores de Risco
10.
Trop Med Int Health ; 16(1): 67-73, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21371209

RESUMO

OBJECTIVE: To evaluate retrospectively the microbiological profile of Mycobacterium species isolated from HIV-infected patients attending the HIV/TB reference health care units in São José do Rio Preto, Brazil. METHOD: Retrospective evaluation of all HIV-1 positive patients whose IAL-SJRP laboratorial analysis was positive for Mycobacterium sp. after diagnosis of HIV Infection, from January 2000 to December 2006. RESULTS: Of 198 patients, acid-fast staining detected mycobacteria early in 41%. Culture revealed 52.5% to be infected with Mycobacterium tuberculosis (MT). 42.4% had non-tuberculous mycobacteria (NTM) and 5.1% had MT/NTM positive cultures. Eleven per cent of MT strains were resistant to at least one of the antimycobacterial drugs and 3.1% were multidrug resistant. 39.4% of isolated mycobacteria were NTM species. CONCLUSION: Our data may serve as a starting point for further comparisons with other Brazilian regions and other developing countries. The data may provide important clues to the future understanding, prevention and control of such co-infections around the world.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/complicações , HIV-1 , Infecções por Mycobacterium/complicações , Mycobacterium/isolamento & purificação , Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Adulto , Idoso , Terapia Antirretroviral de Alta Atividade , Farmacorresistência Bacteriana , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Mycobacterium/classificação , Mycobacterium/efeitos dos fármacos , Infecções por Mycobacterium/microbiologia , Estudos Retrospectivos , Tuberculose/complicações , Adulto Jovem
11.
Am J Trop Med Hyg ; 84(2 Suppl): 58-63, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21292879

RESUMO

Frequency and levels of IgG antibodies to an N-terminal fragment of the Plasmodium vivax MSP-1 (Pv200L) protein, in individuals naturally exposed to malaria in four endemic areas of Brazil, were evaluated by enzyme-linked immunosorbent assay. Plasma samples of 261 P. vivax-infected individuals from communities of Macapá, Novo Repartimento, Porto Velho, and Plácido de Castro in the Amazonian region with different malaria transmission intensities. A high mean number of studied individuals (89.3%) presented with antibodies to the Pv200L that correlated with the number of previous malaria infections; there were significant differences in the frequency of the responders (71.9-98.7) and in the antibody levels (1:200-1:51,200) among the four study areas. Results of this study provide evidence that Pv200L is a naturally immunogenic fragment of the PvMSP-1 and is associated with the degree of exposure to parasites. The fine specificity of antibodies to Pv200L is currently being assessed.


Assuntos
Anticorpos Antiprotozoários/sangue , Malária Vivax/epidemiologia , Proteína 1 de Superfície de Merozoito/imunologia , Plasmodium vivax/imunologia , Animais , Anticorpos Antiprotozoários/biossíntese , Brasil/epidemiologia , Ensaio de Imunoadsorção Enzimática , Humanos , Imunoglobulina G/biossíntese , Imunoglobulina G/sangue , Malária Vivax/imunologia , Malária Vivax/parasitologia , Proteína 1 de Superfície de Merozoito/química
12.
Malar J ; 9: 178, 2010 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-20573199

RESUMO

BACKGROUND: Plasmodium vivax circumsporozoite variants have been identified in several geographical areas. The real implication of the genetic variation in this region of the P. vivax genome has been questioned for a long time. Although previous studies have observed significant association between VK210 and the Duffy blood group, we present here that evidences of this variation are limited to the CSP central portion. METHODS: The phylogenetic analyses were accomplished starting from the amplification of conserved domains of 18 SSU RNAr and Cyt B. The antibodies responses against the CSP peptides, MSP-1, AMA-1 and DBP were detected by ELISA, in plasma samples of individuals infected with two P. vivax CS genotypes: VK210 and P. vivax-like. RESULTS: These analyses of the two markers demonstrate high similarity among the P. vivax CS genotypes and surprisingly showed diversity equal to zero between VK210 and P. vivax-like, positioning these CS genotypes in the same clade. A high frequency IgG antibody against the N- and C-terminal regions of the P. vivax CSP was found as compared to the immune response to the R- and V- repetitive regions (p = 0.0005, Fisher's Exact test). This difference was more pronounced when the P. vivax-like variant was present in the infection (p = 0.003, Fisher's Exact test). A high frequency of antibody response against MSP-1 and AMA-1 peptides was observed for all P. vivax CS genotypes in comparison to the same frequency for DBP. CONCLUSIONS: This results target that the differences among the P. vivax CS variants are restrict to the central repeated region of the protein, mostly nucleotide variation with important serological consequences.


Assuntos
Variação Genética , Proteína 1 de Superfície de Merozoito/genética , Plasmodium vivax/genética , Antígenos de Protozoários/genética , Antígenos de Protozoários/imunologia , Citocromos b/genética , Genótipo , Humanos , Malária Vivax/parasitologia , Proteínas de Membrana/genética , Proteínas de Membrana/imunologia , Proteína 1 de Superfície de Merozoito/imunologia , Dados de Sequência Molecular , Filogenia , Plasmodium vivax/classificação , Reação em Cadeia da Polimerase , Proteínas de Protozoários/genética , Proteínas de Protozoários/imunologia , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/imunologia , Sequências Repetitivas de Ácido Nucleico , Análise de Sequência de DNA
13.
Trans R Soc Trop Med Hyg ; 103(7): 672-8, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18804827

RESUMO

The circumsporozoite protein (CSP) of the Plasmodium vivax infective sporozoite is considered to be a major target for the development of recombinant malaria vaccines. The Duffy blood group molecule acts as the red blood cell receptor for P. vivax. We review the frequency of P. vivax CSP variants and report their association with the Duffy blood group genotypes from Brazilian Amazon patients carrying P. vivax malaria. Peripheral blood samples were collected from 155 P. vivax-infected individuals from five Brazilian malaria-endemic areas. The P. vivax CSP variants and the Duffy blood group genotypes were assessed using PCR/RFLP. In single infections, the VK210 variant was the commonest followed by the P. vivax-like variant. The typing of P. vivax indicated that the frequency of variants among the study areas was significantly different from one to another. This is the first detection of the VK247 and P. vivax-like variant in single infections in endemic areas of Brazil. Association of the CSP P. vivax variants with the heterozygous Duffy blood group system genotype was significant for VK210 single infection. These observations provide additional data on the Plasmodium-host interactions concerning the Duffy blood group and P. vivax capability of causing human malaria.


Assuntos
Sistema do Grupo Sanguíneo Duffy/genética , Malária Vivax/sangue , Plasmodium vivax , Proteínas de Protozoários/sangue , Animais , Brasil , Feminino , Variação Genética/fisiologia , Genótipo , Humanos , Masculino , Reação em Cadeia da Polimerase/métodos , Proteínas de Protozoários/classificação
14.
Malar J ; 6: 167, 2007 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-18093292

RESUMO

BACKGROUND: Duffy blood group polymorphisms are important in areas where Plasmodium vivax predominates, because this molecule acts as a receptor for this protozoan. In the present study, Duffy blood group genotyping in P. vivax malaria patients from four different Brazilian endemic areas is reported, exploring significant associations between blood group variants and susceptibility or resistance to malaria. METHODS: The P. vivax identification was determined by non-genotypic and genotypic screening tests. The Duffy blood group was genotyped by PCR/RFLP in 330 blood donors and 312 malaria patients from four Brazilian Amazon areas. In order to assess the variables significance and to obtain independence among the proportions, the Fisher's exact test was used. RESULTS: The data show a high frequency of the FYA/FYB genotype, followed by FYB/FYB, FYA/FYA, FYA/FYB-33 and FYB/FYB-33. Low frequencies were detected for the FYA/FYX, FYB/FYX, FYX/FYX and FYB-33/FYB-33 genotypes. Negative Duffy genotype (FYB-33/FYB-33) was found in both groups: individuals infected and non-infected (blood donors). No individual carried the FYX/FYB-33 genotype. Some of the Duffy genotypes frequencies showed significant differences between donors and malaria patients. CONCLUSION: The obtained data suggest that individuals with the FYA/FYB genotype have higher susceptibility to malaria. The presence of the FYB-33 allele may be a selective advantage in the population, reducing the rate of infection by P. vivax in this region. Additional efforts may contribute to better elucidate the physiopathologic differences in this parasite/host relationship in regions endemic for P. vivax malaria, in particular the Brazilian Amazon region.


Assuntos
Sistema do Grupo Sanguíneo Duffy/genética , Malária Vivax/genética , Adolescente , Adulto , Alelos , Animais , Doadores de Sangue , Brasil/epidemiologia , Feminino , Genótipo , Humanos , Malária Vivax/sangue , Malária Vivax/epidemiologia , Malária Vivax/parasitologia , Masculino , Polimorfismo de Fragmento de Restrição
15.
Am J Trop Med Hyg ; 77(5): 977-83, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17984363

RESUMO

Antibody responses to malaria invasion ligands and proteins on the merozoite surface have been shown to interfere with red cell invasion and correlate with immunity to malaria. The current study is the first to characterize the antibody responses to EBA-140 and EBA-181, Plasmodium falciparum invasion ligands implicated in the alternative pathways of invasion, in age-matched populations of individuals living in endemic areas in both Brazil and Cameroon. Antibody responses to the proteins screened were different between populations. The African individuals reacted strongly with most fragments of these two EBAs, while the majority of the individuals from Mato Grosso, Brazil, reacted weakly and those from the Amazon had elevated responses to these EBA proteins. When compared with the responses against MSP-1(19) and EBA-175, it appeared that the Brazilian population has a variable ability to recognize P. falciparum invasion ligand proteins and that these responses are distinct from the African population.


Assuntos
Anticorpos Antiprotozoários/imunologia , Malária Falciparum/imunologia , Plasmodium falciparum/metabolismo , Proteínas de Protozoários/imunologia , Adulto , Distribuição por Idade , Animais , Brasil/epidemiologia , Camarões/epidemiologia , Doenças Endêmicas , Regulação da Expressão Gênica , Humanos , Plasmodium falciparum/imunologia , Proteínas de Protozoários/metabolismo , Proteínas Recombinantes/imunologia
16.
Mem Inst Oswaldo Cruz ; 101(5): 547-50, 2006 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17072460

RESUMO

The susceptibility of Anopheles aquasalis (F3 generation) and An. darlingi (F1 generation) to Plasmodium vivax circumsporozoite protein phenotypes from a limited number of blood samples of malaria patients in Belém, state of Pará, Brazil, was examined A polymerase chain reaction was used to determine the P. vivax phenotypes in blood samples and the blood-fed infected mosquitoes were dissected and tested by ELISA. In all patient infections, more infected An. aquasalis and An. darlingi were positive for VK210 compared with VK247.


Assuntos
Anopheles/parasitologia , Insetos Vetores/parasitologia , Plasmodium vivax/fisiologia , Animais , Anopheles/classificação , Ensaio de Imunoadsorção Enzimática , Feminino , Interações Hospedeiro-Parasita/fisiologia , Humanos , Insetos Vetores/classificação , Fenótipo , Plasmodium vivax/genética , Reação em Cadeia da Polimerase
17.
Mem. Inst. Oswaldo Cruz ; 101(5): 547-550, Aug. 2006. tab
Artigo em Inglês | LILACS | ID: lil-437040

RESUMO

The susceptibility of Anopheles aquasalis (F3 generation) and An. darlingi (F1 generation) to Plasmodium vivax circumsporozoite protein phenotypes from a limited number of blood samples of malaria patients in Belém, state of Pará, Brazil, was examined. A polymerase chain reaction was used to determine the P. vivax phenotypes in blood samples and the blood-fed infected mosquitoes were dissected and tested by ELISA. In all patient infections, more infected An. aquasalis and An. darlingi were positive for VK210 compared with VK247.


Assuntos
Humanos , Animais , Feminino , Anopheles/parasitologia , Insetos Vetores/parasitologia , Plasmodium vivax/fisiologia , Anopheles/classificação , DNA de Protozoário , Ensaio de Imunoadsorção Enzimática , Interações Hospedeiro-Parasita/fisiologia , Insetos Vetores/classificação , Fenótipo , Reação em Cadeia da Polimerase , Plasmodium vivax/genética
18.
J Infect Dis ; 190(9): 1547-55, 2004 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-15478058

RESUMO

After a major increase in incidence between the 1970s and the 1990s, the Brazilian Amazon region now accounts for the most cases of Plasmodium falciparum malaria in the Americas. Polymorphism of 10 microsatellite loci in the P. falciparum genome was studied in 196 isolates obtained from 5 populations in the region. There was significant multilocus linkage disequilibrium, particularly within populations with lower proportions of mixed-genotype infections. However, most multilocus genotypes in different isolates were distinct, and there was no evidence of any recent epidemic expansion of particular clones. Genetic divergence between populations was very substantial but did not fit a simple model of isolation by distance. Thus, different foci of P. falciparum in Brazil are quite independent, with distinct population structures and minimal gene flow, a finding that has implications for strategies to control infection and to contain the spread of drug resistance at a regional level.


Assuntos
Genes de Protozoários , Malária Falciparum/parasitologia , Plasmodium falciparum/genética , Plasmodium falciparum/isolamento & purificação , Animais , Brasil/epidemiologia , DNA de Protozoário/análise , DNA de Protozoário/isolamento & purificação , Frequência do Gene , Variação Genética , Genótipo , Haplótipos , Heterozigoto , Humanos , Desequilíbrio de Ligação , Malária Falciparum/epidemiologia , Malária Falciparum/transmissão , Repetições de Microssatélites , Epidemiologia Molecular , Plasmodium falciparum/classificação , Polimorfismo Genético
19.
Rev. bras. hematol. hemoter ; 25(4): 263-265, out.-dez. 2003. ilus, graf
Artigo em Português | LILACS | ID: lil-359497

RESUMO

In malaria endemic regions of Africa, resistance to infection by Plasmodium has been observed in under 6-month-old children, when there are higher fetal hemoglobin (Hb F) levels. Research performed in the São José do Rio Preto region, central-east Brazil, reported increased levels of Hb F in blood donors. The purpose of this work was to evaluate the A2 hemoglobin (Hb A2) and Hb F concentrations in blood donors deriving from the Brazilian malaria endemic region. Forty-five blood donor samples from Macapá, from patients with varying genders, ages and ethnic origins, were collected by venous puncture after informed consent was obtained. The samples were analyzed by High Performance Liquid Chromatography (HPLC) - System Variant (Bio-Rad). The HPLC demonstrated sensitivity and rapidity in the identification and measurement of the hemoglobins and gave precise results. Moreover, it provided measurement of hemoglobin variants, even when they were present in small amounts, providing a diagnosis of hemoglobinopathies. Hb F levels above the normal were observed in 33.3 percent of the analyzed samples. The presence of increased Hb F can suggest resistance to infection by Plasmodium falciparum, as there have been reports that infected red blood cells interfere in the development of the parasite.


Assuntos
Humanos , Doadores de Sangue , Hemoglobinas , Malária , Polimorfismo Genético
20.
Ciênc. cult. (Säo Paulo) ; 52(4/5): 208-12, jul.-out. 2000. ilus, mapas, tab
Artigo em Inglês | LILACS | ID: lil-278774

RESUMO

No Brasil, a malária está restrita à regiäo amazônica, onde ocorre mais de 95 por cento dos casos registrados no país. Somente as fêmeas de mosquitos do gênero Anopheles säo capazes de transmitir os parasitos da malária humana. Treze espécies de anofelinos do Brasil foram encontradas naturalmente infectadas com Plasmodium, mas somente poucas estäo envolvidas na transmissäo. Anopheles darlingi é o principal vetor de malária nas ecorregiões de savana e floresta plana enquanto que o A. aquasalis é responsável pela transmissäo desta infecçäo na área costeira. Todavia, A. deaneorum, A. oswaldoi e A. marajoara tem sido incriminados como vetores locais de malária. Controlar a transmissäo de malária na regisäo Amazônica é uma tarefa muito difícil por causa de suas características ecológicas, ambientais, sociais e econômicas. Nos últimos 10 anos, os assentamentos desordenados (invasões) têm sido uma das principais causas de disseminaçäo de malária humana nos grandes centros urbanos, como é o caso da cidade de Manaus e Belém.


Assuntos
Humanos , Animais , Anopheles , Insetos Vetores , Malária/transmissão , Anopheles/patogenicidade , Brasil , Insetos Vetores/patogenicidade , Malária Falciparum/prevenção & controle , Plasmodium falciparum/patogenicidade
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