Biomedical subjects

Ananias A Escalante

Publications and source records attributed to Ananias A Escalante.

14 recordsLinked to original sources

PubMed2026

Malaria Risk among Internally Mobile Individuals and Heterogeneous Mobility Patterns in Two Hypoendemic Communities: Implications for Malaria Elimination in the Peruvian Amazon.

BACKGROUND: Human mobility is increasingly recognized as a key factor influencing malaria transmission dynamics, particularly in low-transmission settings approaching elimination. This study aimed to assess mobility patterns and their association with malaria risk in two hypoendemic communities in the Peruvian Amazon. METHOD: A longitudinal study was conducted in the communities of Libertad and Urcomiraño (Mazán River basin). Monthly population screenings were combined with weekly active and passive case detection. A total of 678 individuals were enrolled. Mobility patterns were assessed through structured questionnaires, and social network analysis was used to characterize travel connections. Log-binomial regression analysis was applied to identify risk factors associated with malaria infection. RESULT: Internally, mobile individuals in Libertad showed a higher malaria incidence (>32.47 cases per 1,000 person-months) than those in Urcomiraño (<10.15 cases per 1,000 person-months). Travel networks were mainly connected to Mazan district and Iquitos city, followed by local streams such as Armas and Arahuana. Mobility was primarily driven by family, administrative and occupational activities. Male sex (PR = 2.15, 95% CI: 1.37 - 3.37) and age ≥15 years (PR = 1.98, 95% CI: 1.24 - 3.19) were significantly associated with malaria infection (p-value < 0.05). CONCLUSION: Internally mobile populations represent a key high-risk group sustaining malaria transmission in hypoendemic settings. Targeted interventions focusing on mobile individuals should be integrated into malaria elimination strategies in the Peruvian Amazon and similar endemic regions.

Malaria elimination↗

PubMed2006

The origin and age of Plasmodium vivax.

The evolutionary history of Plasmodium vivax has recently been addressed in terms of its origin as a parasite of humans and the age of extant populations. The consensus is that P. vivax originated as a result of a host switch from a non-human primate to hominids and that the extant populations did not originate as recently as previously proposed. Here, we show that, in a comparison of parasite isolates from across the world, Asian populations of P. vivax are the oldest. We discuss how this result, together with the phylogenetic evidence that P. vivax derived from Plasmodium found in Southeast Asian macaques, is most simply explained by assuming an Asian origin of this parasite. Nevertheless, the available data show only the tip of the iceberg. We discuss how sampling might affect time estimates to the most recent common ancestor for P. vivax populations and suggest that spatially explicit estimates are needed to understand the demographic history of this parasite better.

Animals↗

PubMed2006

A comparative study of the genetic diversity of the 42kDa fragment of the merozoite surface protein 1 in Plasmodium falciparum and P. vivax.

We investigated the genetic diversity of the 42kDa fragment of the merozoite surface protein 1 (MSP-1) antigen in Plasmodium falciparum and P. vivax, as well as in non-human primate malarial parasites. This fragment undergoes a proteolytic cleavage generating two fragments of 19kDa (MSP-1(19)) and 33kDa (MSP-1(33)) that are critical in erythrocyte invasion. We found that overall the MSP-1(33) fragment exhibits greater genetic diversity than the MSP-1(19) regardless of the species. We have found evidence for positive natural selection only in the human malaria parasites by comparing the rate of non-synonymous versus synonymous substitutions. In addition, we found clear differences between the two major human malaria parasites. In the case of P. falciparum, positive natural selection is acting on the MSP-1(19) region while the MSP-1(33) is neutral or under purifying selection. The opposite pattern was observed in P. vivax. Our results suggest different roles of this antigen in the host-parasite immune interaction in each of the major human malarial parasites.

Amino Acid Motifs↗

PubMed2006

Pyrosequencing, a high-throughput method for detecting single nucleotide polymorphisms in the dihydrofolate reductase and dihydropteroate synthetase genes of Plasmodium falciparum.

A pyrosequencing protocol was developed as a rapid and reliable method to identify the mutations of the dhfr and dhps genes of Plasmodium falciparum that are associated with antifolate resistance. The accuracy and specificity of this method were tested using six laboratory-cultured P. falciparum isolates harboring known single nucleotide polymorphisms (SNPs) in the genes dhfr (codons 50, 51, 59, 108, and 164) and dhps (codons 436, 437, 540, 581, and 613). The lowest threshold for detection of all the SNPs tested by pyrosequencing was the equivalent of two to four parasite genomes. Also, this method was highly specific for P. falciparum, as it did not amplify any DNA products from the other species of human malaria parasites. We also mixed wild-type and mutant-type parasite DNAs in various proportions to determine how pyrosequencing, restriction fragment length polymorphism (RFLP), and direct conventional sequencing (for dhfr) compared with each other in detecting different SNPs in the mixture. In general, pyrosequencing and RFLP showed comparable sensitivities in detecting most of the SNPs in dhfr except for the 164L mutation, which required at least twice the amount of DNA for pyroseqencing as for RFLP. For detecting SNPs in dhps, pyrosequencing was slightly more sensitive than RFLP and direct sequencing. Overall, pyrosequencing was faster and less expensive than either RFLP or direct sequencing. Thus, pyrosequencing is a practical alternative method that can be used in a high-throughput format for molecular surveillance of antimalarial-drug resistance.

Animals↗

PubMed2006

Antifolate resistance in Plasmodium falciparum: multiple origins and identification of novel dhfr alleles.

BACKGROUND: Sulfadoxine-pyrimethamine has been widely used as first-line therapy for uncomplicated malaria throughout sub-Saharan Africa. Recent studies conducted in Asia and Africa suggest the triple-mutant dhfr genotype (51I/59R/108N) may have been generated as a single event in Southeast Asia, with subsequent spread of the single lineage to the African continent, but this hypothesis needs further validation. METHODS: Direct sequencing of polymerase chain reaction (PCR) products, pyrosequencing, and cloning of PCR products were utilized to identify mutations in dhfr. To investigate the evolutionary history of dhfr alleles, we assayed microsatellite loci flanking dhfr along chromosome 4. RESULTS: A total of 15 of 479 samples from western Kenya showed the presence of I164L, in 5 different genotypes. We document C50R in 2 of our samples. Using microsatellite markers, we show 2 haplotypes for both the 51I/108N/164L and 51I/59R/108N/164L genotypes. Our results also show multiple lineages for the triple-mutant dhfr genotype in Africa. CONCLUSIONS: These findings highlight the importance of local characterization of alleles before molecular surveillance of drug-resistant alleles is considered in different endemic settings and populations.

Alleles↗

PubMed2005

A monkey's tale: the origin of Plasmodium vivax as a human malaria parasite.

The high prevalence of Duffy negativity (lack of the Duffy blood group antigen) among human populations in sub-Saharan Africa has been used to argue that Plasmodium vivax originated on that continent. Here, we investigate the phylogenetic relationships among 10 species of Plasmodium that infect primates by using three genes, two nuclear (beta-tubulin and cell division cycle 2) and a gene from the plastid genome (the elongation factor Tu). We find compelling evidence that P. vivax is derived from a species that inhabited macaques in Southeast Asia. Specifically, those phylogenies that include P. vivax as an ancient lineage from which all of the macaque parasites could originate are significantly less likely to explain the data. We estimate the time to the most recent common ancestor at four neutral gene loci from Asian and South American isolates (a minimum sample of seven isolates per locus). Our analysis estimates that the extant populations of P. vivax originated between 45,680 and 81,607 years ago. The phylogeny and the estimated time frame for the origination of current P. vivax populations are consistent with an "out of Asia" origin for P. vivax as hominoid parasite. The current debate regarding how the Duffy negative trait became fixed in Africa needs to be revisited, taking into account not only human genetic data but also the genetic diversity observed in the extant P. vivax populations and the phylogeny of the genus Plasmodium.

Africa↗

PubMed2004

Genetic distance in housekeeping genes between Plasmodium falciparum and Plasmodium reichenowi and within P. falciparum.

The time to the most recent common ancestor of the extant populations of Plasmodium falciparum is controversial. The controversy primarily stems from the limited availability of sequences from Plasmodium reichenowi, a chimpanzee malaria parasite closely related to P. falciparum. Since the rate of nucleotide substitution differs in different loci and DNA regions, the estimation of genetic distance between P. falciparum and P. reichenowi should be performed using orthologous sequences that are evolving neutrally. Here, we obtained full-length sequences of two housekeeping genes, sarcoplasmic and endoplasmic reticulum Ca2+ -ATPase (serca) and lactate dehydrogenase (ldh), from 11 isolates of P. falciparum and 1 isolate of P. reichenowi and estimate the interspecific genetic distance (divergence) between the two species and intraspecific genetic distance (polymorphism) within P. falciparum. Interspecific distance and intraspecific distance at synonymous sites of interspecies-conserved regions of serca and ldh were 0.0672 +/- 0.0088 and 0.0011 +/- 0.0007, respectively, using the Nei and Gojobori method. Based on the ratio of interspecific distance to intraspecific distance, the time to the most recent common ancestor of P. falciparum was estimated to be (8.30 +/- 5.40) x 10(4) and (11.62 +/- 7.56) x 10(4) years ago, assuming the divergence time of the two parasite species to be 5 and 7 million years ago, respectively.

Amino Acid Sequence↗

PubMed2004

Assessing the effect of natural selection in malaria parasites.

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.

Animals↗

PubMed2003

The genetic diversity of Plasmodium vivax populations.

Little is known of the genetic diversity and population structure of Plasmodium vivax, a debilitating and highly prevalent malaria parasite of humans. This article reviews the known polymorphic genetic markers, summarizes current data on the population structure of this parasite and discusses future prospects for using knowledge of the genetic diversity to improve control measures.

Animals↗

PubMed2002

Diversity and evolution of the envelope gene of dengue virus type 1.

The genetic diversity and phylogenetic relationships of a collection of strains of dengue virus type 1 (DV-1), isolated from different parts of the world, were investigated. Phylogenetic trees derived from the complete sequence of the E gene of 44 strains suggested the existence of five genetic types defined by a maximum nucleotide divergence within each group of 6%. The 22 strains from America were classified into a single genetic type that included strains associated either with classical dengue or hemorrhagic dengue episodes. Using a maximum likelihood procedure based on a single rate with dated tips model and substitution rates calculated at the third codon position, evolution of the five DV-1 genotypes was shown to conform to a molecular clock. The average rate of evolution was estimated to be approximately 16.2 x 10(-4) substitutions/third codon position site/year. Using this estimate, divergence among the DV-1 genotypes was calculated to have occurred approximately 100 years ago. Very low average value of the ratio of nonsynonymous-to-synonymous nucleotide substitutions, relative to the respective sites (0.046), indicated that the evolution of the E gene of the DV-1 is subject mostly to purifying selection.

Dengue↗

PubMed2002

Polymorphism in the gene encoding the Pfs48/45 antigen of Plasmodium falciparum. XI. Asembo Bay Cohort Project.

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.

Alleles↗

PubMed2002

Phylogenetic analysis of the genus Plasmodium based on the gene encoding adenylosuccinate lyase.

Phylogenetic studies of the genus Plasmodium have been performed using sequences of the nuclear, mitochondrial and plastid genes. Here we have analyzed the adenylosuccinate lyase (ASL) gene, which encodes an enzyme involved in the salvage of host purines needed by malaria parasites for DNA synthesis. The ASL gene is present in several eukaryotic as well as prokaryotic organisms and does not have repeat regions, which facilitates the accuracy of the alignment. Furthermore, it has been shown that ASL is not subject to positive natural selection. We have sequenced the ASL gene of several different Plasmodium species infecting humans, rodents, monkeys and birds and used the obtained sequences along with the previously known P. falciparum ASL sequence, for structural and phylogenetic analysis of the genus Plasmodium. The genetic divergence of ASL is comparable with that observed in other nuclear genes such as cysteine proteinase, although ASL cannot be considered conserved when compared to aldolase or superoxide dismutase, which exhibit a slower rate of evolution. Nevertheless, a protein like ASL has a rate of evolution that provides enough information for elucidating evolutionary relationships. We modeled 3D structures of the ASL protein based on sequences used in the phylogenetic analysis and obtained a consistent structure for four different species despite the divergence observed. Such models would facilitate alignment in further studies with a greater number of plasmodial species or other Apicomplexa.

Adenylosuccinate Lyase↗

PubMedDate not supplied

A study of genetic diversity in the gene encoding the circumsporozoite protein (CSP) of Plasmodium falciparum from different transmission areas--XVI. Asembo Bay Cohort Project.

We have investigated the genetic diversity of the gene encoding the CS protein. A total of 75 complete and 96 partial sequences are studied. We find high levels of genetic polymorphisms as evidenced by 50 and 24 alleles at the Th2R and Th3R epitopes, respectively. Overall, we find that African isolates are more polymorphic as compared with parasites from other geographic regions. We conclude that the uneven geographic polymorphism may have an adverse impact on the effectiveness of vaccines based on this antigen alone. We find extensive polymorphism in the repeat allotypes, or RATs. In order to explore how the protein structure may impose restrictions in the number of repeats, we have simulated the stability of the structure of the tandem repeat region. Our analysis suggests that the protein structure may play an important role in the observed polymorphism in the number of CS repeats in Plasmodium falciparum. We explored the linkage and recombination events among the polymorphic sites. We found that putative recombination events overlap with linked sites. We discuss how this pattern is explained by the action of positive natural selection, where the recombination events detected are convergent mutations. We conclude that it is inappropriate to use linkage-recombination patterns on genes under positive selection for assessing the structure of parasite populations.

Alleles↗

PubMedDate not supplied

Evidence for intragenic recombination in Plasmodium falciparum: identification of a novel allele family in block 2 of merozoite surface protein-1: Asembo Bay Area Cohort Project XIV.

We have investigated intragenic recombination in Block 2 of the merozoite surface protein-1 (MSP-1), where three allele-specific families: K1, Mad20, and RO33 were previously known. Using parasites from western Kenya, we have found a fourth Block 2 allele type, which is a recombinant between Mad20 and RO33 alleles. These recombinant alleles, which we have termed MR, contain sequence from the 5' region of Mad20 and the 3' region of RO33. The results of this study provide new data on the complexity of the MSP-1 antigen gene, which is a candidate vaccine antigen, and further support the importance of intragenic recombination in generating genetic variability in Plasmodium falciparum parasites in nature.

Alleles↗