RESUMO
There are few concepts that have been used across disciplines; one of them is natural selection. The impact that this process has on parasite genetic diversity is reviewed here by discussing examples on drug resistance and vaccine antigens. Emphasis is made on how mechanisms need to be addressed rather than associations, and how such investigations were out of reach of biomedical researchers only a decade ago.
Assuntos
Malária/parasitologia , Plasmodium falciparum/genética , Seleção Genética , Animais , Antígenos de Protozoários/genética , Antígenos de Protozoários/imunologia , Evolução Biológica , Interações Hospedeiro-Parasita , Humanos , Malária/imunologia , Vacinas Antimaláricas/farmacologia , Fenótipo , Plasmodium falciparum/crescimento & desenvolvimentoAssuntos
Criptosporidiose/genética , Cryptosporidium/genética , Infecções por HIV/parasitologia , Adulto , Animais , Fezes/parasitologia , Genótipo , Homossexualidade Masculina , Humanos , Masculino , Dados de Sequência Molecular , Peru , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Suínos , Doenças dos Suínos/genética , Doenças dos Suínos/parasitologiaRESUMO
We have investigated the genetic diversity of the gene encoding the transmission-blocking vaccine antigen Pfs48/45 of Plasmodium falciparum parasites from western Kenya and compared it with parasite populations from Thailand, India, and Venezuela. We report 44 complete new sequences. Overall, the antigen is less polymorphic as compared with other pre-erythrocytic and blood stage antigens. Contrary to other P. falciparum antigens, the number of synonymous substitutions per synonymous site exceeds the number of non-synonymous substitutions per non-synonymous site. We have found that the Pfs48/45 gene of Kenyan parasites is more polymorphic than parasites from other geographic origins. Our analysis reveals that positive natural selection is involved in the maintenance of the observed polymorphism. No evidence of intragenic recombination was found. F(st) values reveal high levels of gene flow between India and Thailand, however, there are strong constraints in gene flow among Kenyan, Southeast Asian, and Venezuelan parasites. No alleles could be linked to a specific geographic region. The results of this study suggest that this gametocyte antigen, like other asexual blood stage antigens, is under selection pressure.
Assuntos
Antígenos de Protozoários/genética , Glicoproteínas de Membrana/genética , Plasmodium falciparum/genética , Polimorfismo Genético/genética , Proteínas de Protozoários/genética , Alelos , Animais , Sequência de Bases , Evolução Molecular , Frequência do Gene , Geografia , Índia , Quênia , Dados de Sequência Molecular , Seleção Genética , Tailândia , VenezuelaRESUMO
During 1992-1994, 33 malaria cases were reported in two regions in Brazil were few sporadic atypical cases occur, most of them in home owners, who are weekenders, while home caretakers live there permanently. Indirect Flurescent antibody Test (IFLAT), with Plasmodium vivax, and Enzime Linked Immunosorbent Assay (ELISA) with repeat peptides of the circumsporozoite (CS) proteins of the 3 known P. vivax variants and P. malarie/P. brasilianum, were performed on 277 sera, obtained within a 5 to 10 km range of malaria cases. Very rarely did any of these donors recall typical malaria episodes. Blood smears of all but 5 were negative. One of the 5 malaria cases included in our serology was of a home owner, 1 of a permanent resident, 3 from Superintendencia de Controle de Endemias employees who went there to capture mosquitoes. In region 1the prevalence of IFLAT positive sera was 73 per cent and 28 per cent among caretakers, 18 per cent and 9.6 per cent among home owners. In region 2 (3 localities) no distinction was possible between caretakers and home owners, IFAT positivity being 38 per cent, 28 per cent and 7 per cent. The relative percentage of positive anti-CS repeats ELISA, differed for each of the peptides among localities. Dwellings are in the vicinity of woods, where monkeys are frequently seen. The origin of these malaria cases, geographical differences and high seropositivity is discussed.
Assuntos
Humanos , Plasmodium malariae/imunologia , Plasmodium vivax/imunologia , Sorologia , Malária/epidemiologiaRESUMO
Passage of malaria infected blood through a two-layered column composed of acid-washed glass beads and CF 11 cellulose removes white cells from parasitized blood. However, because use of glass beads and CF 11 cellulose requires filtration of infected blood separately through these two resins and the addition of ADP, the procedure is time-consuming and may be inapropriate for use in the field, especially when large numbers of blood samples are to be treated. Our modification of this process yields parasitized cells free of contaminating leukocytes, and because of its operational simplicity, large numbers of blood samples can be processed. Our procedure also compares well with those using expensive commercial Sepacell resins in its ability to separate leukocytes from whole blood. As a test of usefulness in molecular biologic investigations, the parasites obtained from the blood of malaria-infected patients using the modified procedure yield genomic DNA whose single copy gene, the circumsporozite gene, efficiently amplifies by polymerase chain reaction
Assuntos
Inibição de Migração Celular , Celulose , Vidro , Leucócitos/imunologia , MaláriaRESUMO
The circumsporozoite (CS) protein that covers the surface of infectious sporozoites is a candidate antigen in malaria vaccine development. To determine the extent of B-and T-epitope polymorphism and to understand the mechanisms of antigenic variability, we have characterized the CS protein gene of Plasmodium vivax from field isolates representing geographically distant regions of Papua New Guinea (PNG) and Brazil. In the central repeat region of the CS protein in addition to variation in the number of repeats, an array of mutations was observed which suggests that point mutations have le to the emergence of the variant CS repeat sequence ANGA (G/D)(N/D)QPG from GDRA(D/A)GQPA. Outside the repeat region of the protein, the nonsilent nucleotide substitutions of independent origin are localized in three domains of the protein that either harbor known T-cell determinants or are analogous to the Plasmodium falciparum immunodominant determinants, Th2R and Th3R. We have found that, with the exception of one CS clone sequence that was shared by one P. vivax isolate each from PNG and Brazil, the P.vivax CS protein types can be grouped into Papuan and Brazilian types. These results suggest that an in-dept study of parasite population dynamics is required before field trials for vaccine formulations based on polymorphic immunodominant determinants are conducted.