RESUMO
Comparing patterns of genetic variation at multiple loci in the genome of a species can potentially identify loci which are under selection. The large number of polymorphic microsatellites in the malaria parasite Plasmodium falciparum are available markers to screen for selectively important loci. The Pfs48/45 gene on Chromosome 13 encodes an antigenic protein located on the surface of parasite gametes, which is a candidate for a transmission blocking vaccine. Here, genotypic data from 255 P. falciparum isolates are presented, which show that alleles and haplotypes of five single nucleotide polymorphisms (SNPs) in the Pfs48/45 gene are exceptionally skewed in frequency among different P. falciparum populations, compared with alleles at 11 microsatellite loci sampled widely from the parasite genome. Fixation indices measuring inter-population variance in allele frequencies (F(ST)) were in the order of four to seven times higher for Pfs48/45 than for the microsatellites, whether considered (i) among populations within Africa, or (ii) among different continents. Differing mutational processes at microsatellite and SNP loci could generally affect the population structure at these different types of loci, to an unknown extent which deserves further investigation. The highly contrasting population structure may also suggest divergent selection on the amino acid sequence of Pfs48/45 in different populations, which plausibly indicates a role for the protein in determining gamete recognition and compatibility.
Assuntos
Variação Genética/genética , Malária Falciparum/epidemiologia , Glicoproteínas de Membrana/genética , Repetições de Microssatélites/genética , Plasmodium falciparum/genética , Proteínas de Protozoários/genética , África/epidemiologia , Alelos , Animais , Brasil/epidemiologia , Frequência do Gene , Genética Populacional , Haplótipos , Humanos , Malária Falciparum/parasitologia , Malásia/epidemiologia , Plasmodium falciparum/crescimento & desenvolvimento , Polimorfismo de Nucleotídeo ÚnicoRESUMO
The origin and geographical spread of Plasmodium falciparum is here determined by analysis of mitochondrial DNA sequence polymorphism and divergence from its most closely related species P. reichenowi (a rare parasite of chimpanzees). The complete 6 kb mitochondrial genome was sequenced from the single known isolate of P. reichenowi and from four different cultured isolates of P. falciparum, and aligned with the two previously derived P. falciparum sequences. The extremely low synonymous nucleotide polymorphism in P. falciparum (pi=0.0004) contrasts with the divergence at such sites between the two species (kappa=0.1201), and supports a hypothesis that P. falciparum has recently emerged from a single ancestral population. To survey the geographical distribution of mitochondrial haplotypes in P. falciparum, 104 isolates from several endemic areas were typed for each of the identified single nucleotide polymorphisms. The haplotypes show a radiation out of Africa, with unique types in Southeast Asia and South America being related to African types by single nucleotide changes. This indicates that P. falciparum originated in Africa and colonised Southeast Asia and South America separately.
Assuntos
DNA Mitocondrial/genética , Genoma de Protozoário , Malária Falciparum/parasitologia , Plasmodium falciparum/genética , Plasmodium/genética , África , Animais , Sudeste Asiático , DNA de Protozoário/genética , Evolução Molecular , Haplótipos , Humanos , Dados de Sequência Molecular , Plasmodium falciparum/classificação , Polimorfismo de Nucleotídeo Único , Seleção Genética , América do SulRESUMO
Strongyloides stercoralis L3-specific antibody isotype responses amongst individuals with known long-standing (28-46 years) infection were compared with those of 'young' (6-29 years of age) and 'old' (30-80 years of age) infected individuals from an endemic Jamaican population. Characterization of age-dependent isotype patterns in the endemic community showed that immunoglobulin (Ig) G1 responses were significantly inversely correlated with age. Additionally, a trend towards lower IgE levels in the older age group was observed. Comparison with responses amongst known chronically infected individuals showed that IgG1 and IgE levels were similar to those of the 'old' endemic group, but were significantly lower than those of the 'young' group. In contrast, IgA levels were similar in both endemic groups, but were elevated in chronically infected individuals. IgG4 levels were similar in all groups studied. These findings suggest that age correlates with infection chronicity in communities endemic for S. stercoralis, and that individuals acquire infection early in their lives and remain infected into adulthood. Early and sustained upregulation of IgG4 may facilitate the establishment of infection and, in combination with developing IgE hyporesponsiveness, may promote chronic asymptomatic strongyloidiasis. Conversely, upregulated IgA may be involved in controlling chronic infection levels which are reflected in reduced IgG1 production.
Assuntos
Anticorpos Anti-Helmínticos/sangue , Doenças Endêmicas , Estrongiloidíase/imunologia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Criança , Doença Crônica , Humanos , Imunoglobulina A/sangue , Imunoglobulina E/sangue , Imunoglobulina G/sangue , Jamaica , Pessoa de Meia-IdadeRESUMO
Recently described enzyme-linked immunosorbent assay (ELISA) and immunoblot methods for the detection of serum IgG against Strongyloides stercoralis larval antigens were prospectively evaluated for the diagnosis of endemic strongyloidiasis. A modification of the ELISA involved preincubation of sera with Onchocerca gutturosa phosphate-buffered saline-soluble extract to remove cross-reactivity with other helminths. The sensitivity of the ELISA increased from 80% to 85% following preincubation. Similarly, there was an increase in specificity from 94% to 97%. The IgG recognition of 41-, 31-, and 28-kD filariform larval components showed sensitivities of 100%, 85%, and 65%, respectively. Both the ELISA following incubation of sera with O. gutturosa extract and serum IgG reactivity to a 41-kD larval component using immunoblotting are sensitive and specific techniques for diagnosing endemic strongyloidiasis.