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1.
Transfus Clin Biol ; 17(3): 176-83, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20655790

RESUMO

The Duffy blood group antigen is the portal of entry of the Plasmodiumvivax malaria parasite into human red blood cells and the receptor for a number of CXC and CC chemokines. We review here epidemiological data and evidence derived from therapeutic or experimental human infections associating P. vivax and the Duffy glycoprotein and laboratory studies indicating that P. vivax uses the Duffy antigen as a receptor to invade the red cell. We then review recent field observations indicating that the conclusion of the absolute dependence on the presence of Duffy on the red cell for P. vivax infection and development into the red cell no longer holds true and that in some parts of the world, P. vivax infects and causes disease in Duffy-negative people.


Assuntos
Sistema do Grupo Sanguíneo Duffy/genética , Sistema do Grupo Sanguíneo Duffy/imunologia , Eritrócitos/parasitologia , Malária Vivax/imunologia , Plasmodium vivax/imunologia , África/epidemiologia , Animais , Antimaláricos/uso terapêutico , Antígenos de Grupos Sanguíneos/genética , Antígenos de Grupos Sanguíneos/imunologia , Deleção de Genes , Regulação da Expressão Gênica , Humanos , Madagáscar/epidemiologia , Malária Vivax/tratamento farmacológico , Malária Vivax/epidemiologia , Papua Nova Guiné/epidemiologia , Fenótipo , Plasmodium vivax/metabolismo , Índice de Gravidade de Doença , Zoonoses/epidemiologia , Zoonoses/transmissão
2.
Transfus Clin Biol ; 15(1-2): 62-71, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18514562

RESUMO

The capacity of Plasmodium falciparum-infected red blood cells to bind uninfected red blood cells ("rosetting") has been associated with high parasite density in numerous geographic areas and with severe malaria in African children. We summarize here the associations that have emerged from field studies and describe the various experimental models of rosetting that have been developed. A variety of erythrocyte receptors, several serum factors and a number of rosette-mediating PfEMP1 adhesins have been identified. Several var genes code for rosette-forming PfEMP1 adhesins in each P. falciparum genome, so that each clonal line has the capacity to generate distinct types of rosettes. To clarify their respective role in malaria pathogenesis, each of the multiple ligand/receptor interactions should be further studied for fine specificity, binding affinity and the impact of the large population polymorphism of the parasite variant repertoires should be assessed. Interestingly, some major human erythrocyte surface polymorphisms have been identified as affecting rosette formation, consistent with a role for rosetting in life-threatening falciparum malaria.


Assuntos
Adesão Celular/fisiologia , Malária Falciparum/sangue , Plasmodium falciparum/fisiologia , Formação de Roseta , Sistema ABO de Grupos Sanguíneos/imunologia , Animais , Criança , Eritrócitos/parasitologia , Glicoconjugados/fisiologia , Humanos , Imunoglobulina G/fisiologia , Imunoglobulina M/fisiologia , Malária Falciparum/parasitologia , Malária Falciparum/fisiopatologia , Proteínas de Protozoários/genética , Proteínas de Protozoários/fisiologia , Receptores de Complemento/fisiologia , Receptores de Complemento 3b/fisiologia
3.
Proc Natl Acad Sci U S A ; 104(22): 9213-7, 2007 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-17517609

RESUMO

During intraerythrocytic development, Plasmodium falciparum exports proteins that interact with the host cell plasma membrane and subplasma membrane-associated spectrin network. Parasite-exported proteins modify mechanical properties of host RBCs, resulting in altered cell circulation. In this work, optical tweezers experiments of cell mechanical properties at normal physiological and febrile temperatures are coupled, for the first time, with targeted gene disruption techniques to measure the effect of a single parasite-exported protein on host RBC deformability. We investigate Pf155/Ring-infected erythrocyte surface antigen (RESA), a parasite protein transported to the host spectrin network, on deformability of ring-stage parasite-harboring human RBCs. Using a set of parental, gene-disrupted, and revertant isogenic clones, we found that RESA plays a major role in reducing deformability of host cells at the early ring stage of parasite development, but not at more advanced stage. We also show that the effect of RESA on deformability is more pronounced at febrile temperature, which ring-stage parasite-harboring RBCs can be exposed to during a malaria attack, than at normal body temperature.


Assuntos
Forma Celular , Eritrócitos/citologia , Eritrócitos/metabolismo , Plasmodium falciparum/fisiologia , Proteínas de Protozoários/metabolismo , Animais , Humanos , Proteínas de Protozoários/genética , Temperatura , Trofozoítos
5.
Parasite ; 11(4): 419-23, 2004 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-15638145

RESUMO

We report the outcome of chloroquine treatment and the prevalence of mutations at codon 86 of the pfmdr1 gene, at codon 76 of the pfcrt gene, and at codon 108 of the pfdhfr gene in clinical isolates of Plasmodium falciparum collected from 30 children under 10 years of age living in the Comoros Union. This in vivo study was carried out in February and March 2001 in Moroni. Chloroquine treatment failed in 23 children (76.6%; 95% confidence interval: 57.7 to 90.1%). Subsequent genotyping showed that all P. falciparum isolates (100%) harboured a tyrosine residue at position 86 in pfMDR1. 83.3% (25/30) of these isolates harboured a mutation at position 76 in pfCRT and half (15/30) of these isolates also harboured a mutation at position 108 in pfDHFR. Chloroquine resistance is a real concern in the Comoros Union. The prevalence of pfDHFR mutant parasites is alarming. The alternative drugs proposed as a replacement for chloroquine as first-line treatment in Comoros, and the strategy to monitor the drug susceptibility of Plasmodium sp in this part of the Indian Ocean sub-region are discussed.


Assuntos
Antimaláricos/farmacologia , Cloroquina/farmacologia , Malária Falciparum/tratamento farmacológico , Plasmodium falciparum/efeitos dos fármacos , Plasmodium falciparum/genética , Pirimetamina/farmacologia , Animais , Criança , Pré-Escolar , Comores/epidemiologia , DNA de Protozoário/genética , Resistência a Medicamentos/genética , Feminino , Genótipo , Humanos , Lactente , Malária Falciparum/epidemiologia , Malária Falciparum/parasitologia , Masculino , Proteínas de Membrana/genética , Proteínas de Membrana Transportadoras , Mutação , Testes de Sensibilidade Parasitária , Plasmodium falciparum/classificação , Prevalência , Proteínas de Protozoários , Resultado do Tratamento
6.
Med Trop (Mars) ; 63(3): 241-4, 2003.
Artigo em Francês | MEDLINE | ID: mdl-14579459

RESUMO

With the publication of seminal articles on the genomic sequence of Plasmodium falciparum and P. yoelii yoelii last autumn following the articles on genome of Anopheles gambiae, man, and mice, malariology stepped indubitably into a new era. A major finding of genome annotation is that nearly 60% of Plasmodium sp. have no functional attribution and that a high proportion of P. falciparum sequences have no counterpart in P. yoelii. In the light of these findings it will now be possible to explore the specificities of the Plasmodium genus and particularities of each species--and ultimately the relevance of animal malaria models. Numerous avenues of research have been opened not only for drug discovery, vaccine development, dissecting the cascade of events contributing to pathology or protection, but also for population biology studies and analysis of genetic exchanges within field parasite populations. The field has been radically changed, and coordinated efforts are needed to implement the powerful post genomic technologies. There is an urgent need to exploit this huge mass of new data for the development of new control methods. This development requires a rational approach of functional genomics and integrative biology. The purpose of this article is to briefly summarize current data and discuss experimental approaches and perspectives.


Assuntos
Genômica/tendências , Vacinas Antimaláricas , Malária/tratamento farmacológico , Malária/genética , Plasmodium falciparum/genética , Plasmodium falciparum/patogenicidade , Plasmodium yoelii/genética , Plasmodium yoelii/patogenicidade , Animais , Antimaláricos/farmacologia , Genética Populacional , Humanos , Malária/prevenção & controle
7.
Clin Exp Immunol ; 129(2): 326-31, 2002 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12165090

RESUMO

Merozoite surface protein 2 (MSP2) expressed by Plasmodium falciparum asexual blood stages has been identified as a promising vaccine candidate. In order to explore allelic family-specific humoral responses which may be responsible for parasite neutralization during natural infections, isolates from individuals with either asymptomatic infections or uncomplicated malaria and residing in a Central African area where Plasmodium transmission is high and perennial, were analysed using MSP2 as polymorphic marker. The family-specific antibody responses were assessed by ELISA using MSP2 synthetic peptides. We observed an age-dependence of P. falciparum infection complexity. The decrease of infection complexity around 15 years of age was observed simultaneously with an increase in the mean number of MSP2 variants recognized. No significant difference in the P. falciparum genetic diversity and infection complexity was found in isolates from asymptomatic subjects and patients with uncomplicated malaria. The longitudinal follow-up showed a rapid development of immune responses to various regions of MSP2 variants within one week. Comparing humoral responses obtained with the other major antigen on the merozoite surface, MSP1, our findings suggest that different pathways of responsiveness are involved in antibody production to merozoite surface antigens.


Assuntos
Anticorpos Antiprotozoários/sangue , Antígenos de Protozoários/genética , Antígenos de Protozoários/imunologia , Malária Falciparum/imunologia , Plasmodium falciparum/genética , Plasmodium falciparum/imunologia , Proteínas de Protozoários/genética , Proteínas de Protozoários/imunologia , Adolescente , Adulto , Fatores Etários , Alelos , Sequência de Aminoácidos , Animais , Antígenos de Superfície/genética , Criança , Pré-Escolar , Epitopos/genética , Gabão , Variação Genética , Humanos , Imunoglobulina G/sangue , Lactente , Recém-Nascido , Dados de Sequência Molecular , Fragmentos de Peptídeos/genética , Fragmentos de Peptídeos/imunologia
8.
J Infect Dis ; 184(3): 330-6, 2001 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-11443559

RESUMO

A point mutation in the promoter of the nitric oxide synthase 2 gene (NOS2), termed NOS2(Lambaréné) (NOS2-G954C), protects heterozygous carriers against severe malaria as effectively as the sickle cell trait. In a prospective longitudinal study, 841 individual infections of initially 200 children (151 wild-type vs. 49 NOS2(Lambaréné) carriers) were monitored for 4 years, to assess the rates of malarial attacks in the 2 groups; carriers of the NOS2(Lambaréné) polymorphism were significantly less likely to experience malarial attacks than were others (P=.002). The distribution of the NOS2(Lambaréné) polymorphism was investigated in malaria-endemic areas. It was found to be present with the highest frequency in Africa and at a lower frequency in Asia. Ex vivo studies showed that cells isolated from people with this polymorphism have a 7-fold higher baseline NOS activity, compared with the levels detected in cells from subjects with the wild-type gene (P=.003).


Assuntos
Frequência do Gene , Imunidade Inata/genética , Malária/genética , Óxido Nítrico Sintase/genética , Óxido Nítrico Sintase/metabolismo , Óxido Nítrico/biossíntese , Mutação Puntual , Polimorfismo de Nucleotídeo Único , Estudos de Casos e Controles , Criança , DNA/sangue , Feminino , Gabão , Triagem de Portadores Genéticos , Alemanha , Humanos , Malária/fisiopatologia , Masculino , Nigéria , Óxido Nítrico Sintase Tipo II , Papua Nova Guiné , Reação em Cadeia da Polimerase , Senegal , Tailândia
9.
Am J Trop Med Hyg ; 64(5-6): 303-9, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11463122

RESUMO

Pregnancy is associated with a greater susceptibility to Plasmodium falciparum infections, which may result in serious complications affecting both the mother and the fetus. To compare allelic diversity and multiplicity of infection in the same women during and outside pregnancy, we conducted a retrospective analysis of the monthly fingerprick blood samples collected during a longitudinal survey conducted in Ndiop, a Senegalese village with mesoendemic malaria. Merozoite surface protein-1 (msp1) block 2 and merozoite surface protein-2 (msp2) genotypes were determined for 308 blood samples collected from 20 women. Pregnancy was associated with a significantly higher prevalence of P. falciparum infection, higher parasite densities, and a higher multiplicity of infection. The highest multiplicity of infection was observed in the youngest pregnant women. Because of co-linearity, it was not possible to dissociate the impact of age from that of parity on multiplicity of infection. Some individual msp1 and msp2 alleles showed a highly skewed pregnancy-associated distribution. These results indicate that pregnancy is associated with increased permissiveness to a large number of clones, as well as with infection by specific genotypes.


Assuntos
Alelos , Antígenos de Protozoários/genética , Malária Falciparum/epidemiologia , Proteína 1 de Superfície de Merozoito/genética , Plasmodium falciparum/genética , Complicações Parasitárias na Gravidez/epidemiologia , Proteínas de Protozoários/genética , Adolescente , Adulto , Animais , Feminino , Humanos , Malária Falciparum/complicações , Malária Falciparum/genética , Plasmodium falciparum/imunologia , Reação em Cadeia da Polimerase , Gravidez , Estações do Ano , Senegal/epidemiologia
10.
J Infect Dis ; 184(2): 237-41, 2001 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-11424024

RESUMO

Why severe Plasmodium falciparum malaria occurs in only a small percentage of patients is unclear. The possibility that specific parasite characteristics contribute to severity has been investigated in French Guiana, a hypoendemic area, where parasite diversity is low and all patients with severe cases are referred to a single intensive care unit. Parasite genotyping in geographically and temporally matched patients with mild and severe disease showed that the association of a specific msp-1 allele (B-K1) with a specific var gene (var-D) was overrepresented among patients with severe versus mild disease (47% vs. 3%, respectively; P<.001). Moreover, this genotype combination was consistently observed in the most severe clinical cases. Reverse-transcription polymerase chain reaction demonstrated programmed expression of var-D in vivo, which is consistent with its potential implication in severe disease. These results provide field evidence of an association of severe malaria with specific genetic characteristics of parasites and open the way for intervention strategies targeting key virulence factors of parasites.


Assuntos
DNA de Protozoário/análise , Malária Falciparum/diagnóstico , Malária Falciparum/parasitologia , Plasmodium falciparum/classificação , Animais , Guiana Francesa/epidemiologia , Genótipo , Humanos , Malária Falciparum/etnologia , Plasmodium falciparum/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Índice de Gravidade de Doença
11.
Trans R Soc Trop Med Hyg ; 95(2): 225-32, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11355566

RESUMO

Genetic diversity of malaria parasites represents a major issue in understanding several aspects of malaria infection and disease. Genotyping of Plasmodium falciparum infections with polymerase chain reaction (PCR)-based methods has therefore been introduced in epidemiological studies. Polymorphic regions of the msp1, msp2 and glurp genes are the most frequently used markers for genotyping, but methods may differ. A multicentre study was therefore conducted to evaluate the comparability of results from different laboratories when the same samples were analysed. Analyses of laboratory-cloned lines revealed high specificity but varying sensitivity. Detection of low-density clones was hampered in multiclonal infections. Analyses of isolates from Tanzania and Papua New Guinea revealed similar positivity rates with the same allelic types identified. The number of alleles detected per isolate, however, varied systematically between the laboratories especially at high parasite densities. When the analyses were repeated within the laboratories, high agreement was found in getting positive or negative results but with a random variation in the number of alleles detected. The msp2 locus appeared to be the most informative single marker for analyses of multiplicity of infection. Genotyping by PCR is a powerful tool for studies on genetic diversity of P. falciparum but this study has revealed limitations in comparing results on multiplicity of infection derived from different laboratories and emphasizes the need for highly standardized laboratory protocols.


Assuntos
Malária Falciparum/genética , Análise de Variância , Animais , Antígenos de Protozoários/genética , Genótipo , Humanos , Proteína 1 de Superfície de Merozoito/genética , Plasmodium falciparum/genética , Reação em Cadeia da Polimerase/métodos , Polimorfismo de Fragmento de Restrição , Proteínas de Protozoários/genética
12.
Infect Immun ; 69(5): 3190-6, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-11292740

RESUMO

gamma delta T cells have variously been implicated in the protection against, and the pathogenesis of, malaria, but few studies have examined the gamma delta T-cell response to malaria in African children, who suffer the large majority of malaria-associated morbidity and mortality. This is unfortunate, since available data suggest that simple extrapolation of conclusions drawn from studies of nonimmune adults ex vivo and in vitro is not always possible. Here we show that both the frequencies and the absolute numbers of gamma delta T cells are transiently increased following treatment of Plasmodium falciparum malaria in Ghanaian children and they can constitute 30 to 50% of all T cells shortly after initiation of antimalarial chemotherapy. The bulk of the gamma delta T cells involved in this perturbation expressed V delta 1 and had a highly activated phenotype. Analysis of the T-cell receptors (TCR) of the V delta 1(+) cell population at the peak of their increase showed that all expressed V gamma chains were used, and CDR3 length polymorphism indicated that the expanded V delta 1 population was highly polyclonal. A very high proportion of the V delta 1(+) T cells produced gamma interferon, while fewer V delta 1(+) cells than the average proportion of all CD3(+) cells produced tumor necrosis factor alpha. No interleukin 10 production was detected among TCR-gamma delta(+) cells in general or V delta 1(+) cells in particular. Taken together, our data point to an immunoregulatory role of the expanded V delta 1(+) T-cell population in this group of semi-immune P. falciparum malaria patients.


Assuntos
Ativação Linfocitária , Malária Falciparum/imunologia , Receptores de Antígenos de Linfócitos T gama-delta/análise , Subpopulações de Linfócitos T/imunologia , Complexo CD3/análise , Criança , Pré-Escolar , Citocinas/sangue , Humanos , Malária Falciparum/tratamento farmacológico
13.
Eur J Immunol ; 31(2): 539-50, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11180119

RESUMO

The MSP-1 merozoite surface antigen of the human malaria parasite Plasmodium falciparum is a major target of immune response. The domain called block 2 shows extensive allelic diversity, with more than 50 alleles identified, grouped into three allelic families. Presence of anti-block 2 antibodies has been associated with reduced risk for clinical malaria, but whether or not allele-specific antibodies are implicated remains unclear. To study the fine specificity of the human antibody response, we have used a series of 82 overlapping, N-biotinylated, 15-mer peptides scanning reference alleles and including numerous sequence variants. Peptide antigenicity was validated using sera from mice immunized with recombinant proteins. A cross-sectional survey conducted in a Senegalese village with intense malaria transmission indicated an overall 56 % seroprevalence. The response was specific for individuals and unrelated to the HLA type. Each responder reacted to a few peptides, unrelated to the infecting parasite genotype(s). Seroprevalence of each individual peptide was low, with no identifiable immunodominant epitope. Anti-block 2 antibodies were mostly of the IgG3 isotype, consistent with an involvement in cytophilic antibody-mediated merozoite clearance. The number of responders increased with age, but there was no accumulation of novel specificities with age and hence with exposure to an increasingly large number of alleles. A 15-month longitudinal follow up outlined a remarkably fixed response, with identical reactivity profiles, independent of the past or current parasite types, a pattern reminiscent of clonal imprinting. The implications of the characteristics of the anti-block 2 antibody response in parasite clearance are discussed.


Assuntos
Anticorpos Antiprotozoários/sangue , Antígenos de Protozoários/imunologia , Proteína 1 de Superfície de Merozoito/imunologia , Plasmodium falciparum/imunologia , Alelos , Sequência de Aminoácidos , Animais , Epitopos , Teste de Histocompatibilidade , Humanos , Imunização , Imunoglobulina G/sangue , Imunoglobulina G/classificação , Vacinas Antimaláricas/imunologia , Dados de Sequência Molecular , Estudos Soroepidemiológicos , Vacinas Sintéticas/imunologia
14.
Parasite Immunol ; 22(11): 535-43, 2000 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11116433

RESUMO

The Pf72/Hsp70-1 antigen is a major target in the naturally acquired immunity against Plasmodium falciparum malaria. We carried out an extensive analysis of the responses to several epitopes on the least conserved C-terminal domain, according to the mode of sensitization: malaria infection or immunization with different immunogens. We found significant differences in the panel of B-cell epitopes recognized by animal models including primates, and by humans sensitized by natural infection. We focused the analysis on one epitope that is unique to Plasmodium species. It is specifically recognized by a monoclonal antibody that mediates the killing of infected hepatocytes in vitro. We produced a polymeric multiple antigenic peptide (MAP) form of this sequence, which enabled us to identify a new B-cell epitope not detected by ELISA with linear peptides. The polymer was strongly recognized by sera from monkeys or humans sensitized by natural infection, whereas the monomer was not. We modelled the three-dimensional structure of the Pf72/Hsp70-1 sequence, using known Escherischia coli DnaK structures as a template. This predicted that the corresponding region would form a loop in the native antigen. The results presented here suggest that the MAP strategy is also particularly useful as a means of obtaining suitable synthetic models for conformation-dependent epitopes.


Assuntos
Antígenos de Protozoários/imunologia , Epitopos de Linfócito B/imunologia , Proteínas de Choque Térmico/imunologia , Malária Falciparum/imunologia , Peptídeos/imunologia , Plasmodium falciparum/imunologia , Sequência de Aminoácidos , Animais , Anticorpos Antiprotozoários/sangue , Anticorpos Antiprotozoários/imunologia , Antígenos de Protozoários/química , Antígenos de Protozoários/genética , Epitopos de Linfócito B/química , Proteínas de Choque Térmico/química , Humanos , Imunização , Malária Falciparum/parasitologia , Camundongos , Camundongos Endogâmicos BALB C , Mimetismo Molecular , Dados de Sequência Molecular , Peptídeos/síntese química , Peptídeos/química , Peptídeos/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Saimiri
15.
J Clin Microbiol ; 38(11): 4049-57, 2000 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11060067

RESUMO

To gain insight on the significance of human T-cell lymphotropic virus type 1 (HTLV-1) indeterminate serological reactivities, we studied villagers of South Cameroon, focusing on a frequent and specific HTLV-1 Gag indeterminate profile (HGIP) pattern (gag p19, p26, p28, and p30 without p24 or Env gp21 and gp46). Among the 102 sera studied, 29 from all age groups had a stable HGIP pattern over a period of 4 years. There was no epidemiological evidence for sexual or vertical transmission of HGIP. Seventy-five percent of HGIP sera reacted positively on MT2 HTLV-1-infected cells by immunofluorescence assay. However, we could not isolate any HTLV-1 virus or detect the presence of p19 Gag protein in cultures of peripheral blood mononuclear cells obtained from individuals with strong HGIP reactivity. PCR experiments conducted with primers for HTLV-1 and HTLV-2 (HTLV-1/2 primers) encompassing different regions of the virus did not yield HTLV-1/2 proviral sequences from individuals with HGIP. Using 11 peptides corresponding to HTLV-1 or HTLV-2 immunodominant B epitopes in an enzyme-linked immunosorbent assay, one epitope corresponding to the Gag p19 carboxyl terminus was identified in 75% of HGIP sera, while it was recognized by only 41% of confirmed HTLV-1-positive sera. A positive correlation between HTLV-1 optical density values and titers of antibody to Plasmodium falciparum was also demonstrated. Finally, passage of sera through a P. falciparum-infected erythrocyte-coupled column was shown to specifically abrogate HGIP reactivity but not the HTLV-1 pattern, suggesting the existence of cross-reactivity between HTLV-1 Gag proteins and malaria-derived antigens. These data suggest that in Central Africa, this frequent and specific Western blot is not caused by HTLV-1 infection but could instead be associated with P. falciparum infection.


Assuntos
Anticorpos Antideltaretrovirus/sangue , Produtos do Gene gag/imunologia , Infecções por HTLV-I/imunologia , Vírus Linfotrópico T Tipo 1 Humano/imunologia , Malária Falciparum/imunologia , Adulto , Sequência de Aminoácidos , Animais , Anticorpos Antiprotozoários/sangue , Western Blotting , Camarões/epidemiologia , Criança , Reações Cruzadas , DNA Viral/sangue , Antígenos de Deltaretrovirus/imunologia , Ensaio de Imunoadsorção Enzimática , Epitopos/imunologia , Produtos do Gene gag/química , Infecções por HTLV-I/epidemiologia , Infecções por HTLV-I/virologia , Infecções por HTLV-II/imunologia , Infecções por HTLV-II/virologia , Vírus Linfotrópico T Tipo 1 Humano/genética , Vírus Linfotrópico T Tipo 1 Humano/isolamento & purificação , Vírus Linfotrópico T Tipo 1 Humano/metabolismo , Vírus Linfotrópico T Tipo 2 Humano/genética , Vírus Linfotrópico T Tipo 2 Humano/imunologia , Vírus Linfotrópico T Tipo 2 Humano/isolamento & purificação , Vírus Linfotrópico T Tipo 2 Humano/metabolismo , Humanos , Malária Falciparum/parasitologia , Dados de Sequência Molecular , Peptídeos/síntese química , Peptídeos/imunologia , Plasmodium falciparum/imunologia
16.
Microbes Infect ; 2(8): 945-54, 2000 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10962278

RESUMO

Plasmodium falciparum infection in humans leads to a variety of symptoms ranging from an influenza-like syndrome to life-threatening complications. Animal models are useful tools for the detailed analysis of the interaction between both parasite and host factors leading to these various clinical manifestations. In this review, examining the different clinical, parasitological and haematological parameters associated with P. falciparum infection in spleen-intact monkeys, we propose this model as a good alternative for exploring some aspects of the host-parasite relationship in malaria.


Assuntos
Malária Falciparum/fisiopatologia , Anemia/parasitologia , Animais , Modelos Animais de Doenças , Febre/parasitologia , Doenças Hematológicas/parasitologia , Humanos , Leucócitos/citologia , Malária Falciparum/sangue , Malária Falciparum/imunologia , Plasmodium falciparum/fisiologia , Saimiri , Baço/imunologia , Esplenectomia , Trombocitopenia/parasitologia
17.
Parasitol Res ; 86(8): 692-8, 2000 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10952272

RESUMO

For a better definition of the polymorphic features of Plasmodium falciparum parasite populations, the polymerase chain reaction (PCR) typing technique was used to investigate the genetic diversity and complexity of parasites harbored by acute P. falciparum carriers from three yet unexplored malaria-mesoendemic areas with different transmission levels: two localities in northwestern Brazil (Ariquemes and Porto Velho) and a village in Madagascar (Ankazobe). A total of 89 DNA samples were analyzed by amplification of polymorphic domains from genes encoding merozoite surface antigens 1 and 2 (MSP-1, MSP-2) and thrombospondin-related anonymous protein (TRAP) and by hybridization with allelic-family-specific probes or random-fragment-length polymorphism (RFLP). In all three localities, extensive polymorphism was observed for each marker, but the MSP-2 central repeat was the most diverse one. Similar levels of genetic diversity, allelic frequency, and infection complexity were observed in the two Brazilian localities, although the isolates had been sampled at 2-year intervals, suggesting the stability of the infecting parasite populations presenting in these regions of the Brazilian Amazon. Unexpectedly, although the entomologic inoculation rate was at least 3 times lower in Ankazobe than in the Brazilian areas. Malagasi samples appeared more complex than the Brazilian ones. The implications of these data with regard to parasite population-dynamics studies are discussed.


Assuntos
Antígenos de Protozoários/genética , Malária Falciparum/genética , Proteína 1 de Superfície de Merozoito/genética , Proteínas de Protozoários/genética , Animais , Brasil/epidemiologia , Doenças Endêmicas , Variação Genética , Humanos , Madagáscar/epidemiologia , Polimorfismo de Fragmento de Restrição
18.
Vaccine ; 19(1): 59-67, 2000 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-10924787

RESUMO

We have reported previously that the recombinant Glutathione S-transferase GTR23, induced protection after immunisation of naive or previously exposed Saimiri monkeys. We investigated the immunogenicity of carrier-free R23 repeats in pre-exposed animals in two adjuvant formulations. Three of five monkeys immunised with alum-formulated repeats and one of two animals immunised with the Polyalphaolefine formulation produced high titres of cytophilic antibodies with a primary type kinetics, indicating that the anti-P. falciparum antibodies present on the day of challenge were R23-specific. The four responders in R23-specific antibodies were protected against a challenge infection with the virulent FUP/SP strain. The other three animals failed to respond to immunisation and experienced an infection that required drug treatment. Unlike the other three animals that experienced an infection requiring drug treatment. These experiments support further development of the R23 repeats as a vaccine candidate.


Assuntos
Antígenos de Protozoários/administração & dosagem , Malária Falciparum/prevenção & controle , Plasmodium falciparum/imunologia , Adjuvantes Imunológicos/administração & dosagem , Animais , Anticorpos/sangue , Modelos Animais de Doenças , Malária Falciparum/sangue , Malária Falciparum/imunologia , Saimiri , Resultado do Tratamento , Vacinação
19.
Int Immunol ; 12(6): 797-805, 2000 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10837407

RESUMO

TCR gamma delta(+) cells constitute <5% of all circulating T cells in healthy, adult Caucasians, and V(delta)1(+) cells constitute a minority of these cells. In contrast to TCR alpha beta(+) cells, their repertoire is selected extrathymically by environmental antigens. Although increased frequencies of V(delta)1(+) cells are found in several diseases, their function remains obscure. Here we show that the frequency of peripheral blood gamma delta T cells in healthy West Africans is about twice that of Caucasians, mainly due to a 5-fold increase in V(delta)1(+) cells, which is consequently the dominant subset. No age dependency of V(delta)1 frequencies was identified and the V(delta)1(+) cells in the African donors did not show preferential V(gamma) chain usage. Analysis of the CDR3 region size did not reveal any particular skewing of the V(delta)1 repertoire, although oligoclonality was more pronounced in adults compared to children. The proportions of CD8(+), CD38(+) and CD45RA(hi)CD45RO(-) cells within the V(delta)1(+) subset were higher in the African than in the European donors, without obvious differences in expression of activation markers. No significant correlations between levels of V(delta)1(+) cells and environmental antigens or immunological parameters were identified. Taken together, the evidence argues against a CDR3-restricted, antigen-driven expansion of V(delta)1(+) cells in the African study population. Our study shows that high frequencies of TCR gamma delta(+) cells with dominance of the V(delta)1(+) subset can occur at the population level in healthy people, raising questions about the physiological role of V(delta)1(+) T cells in the function and regulation of the immune system.


Assuntos
Receptores de Antígenos de Linfócitos T gama-delta/análise , Subpopulações de Linfócitos T/imunologia , Adulto , Fatores Etários , População Negra , Criança , Humanos , Imunoglobulina G/sangue , Imunofenotipagem , Malária/imunologia , Parasitemia/imunologia , População Branca
20.
Mol Microbiol ; 35(5): 1005-16, 2000 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10712683

RESUMO

Four large multigene families have been described in Plasmodium falciparum malaria parasites (var, rif, stevor and Pf60). var and rif genes code for erythrocyte surface proteins and undergo clonal antigenic variation. We report here the characterization of the first Pf60 gene. The 6.1 gene is constitutively expressed by all mature blood stages and codes for a protein located within the nucleus. It has a single copy, 7-exon, 5' domain, separated by an internal stop codon from a 3' domain that presents a high homology with var exon II. Double-site immunoassay and P. falciparum transient transfection using the reporter luciferase gene demonstrated translation through the internal ochre codon. The 6.1 N-terminal domain has no homology with any protein described to date. Sequence analysis identified a leucine zipper and a putative nuclear localization signal and showed a high probability for coiled coils. Evidence for N-terminal coiled coil-mediated protein interactions was obtained. This identifies the 6.1 protein as a novel nuclear protein. These data show that the Pf60 and var genes form a superfamily with a common 3' domain, possibly involved in regulating homo- or heteromeric interactions.


Assuntos
Códon de Terminação , Família Multigênica , Proteínas Nucleares/genética , Plasmodium falciparum/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Linhagem Celular , Clonagem Molecular , DNA Complementar , Feminino , Humanos , Camundongos , Dados de Sequência Molecular , Fases de Leitura Aberta , Homologia de Sequência de Aminoácidos , Homologia de Sequência do Ácido Nucleico , Transfecção
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