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At least 631 records · Page 35Linked to original sources
PubMed2001

Meiotic recombination, cross-reactivity, and persistence in Plasmodium falciparum.

We incorporate a representation of Plasmodium falciparum recombination within a discrete-event model of malaria transmission. We simulate the introduction of a new parasite genotype into a human population in which another genotype has reached equilibrium prevalence and compare the emergence and persistence of the novel recombinant forms under differing cross-reactivity relationships between the genotypes. Cross-reactivity between the parental (initial and introduced) genotypes reduces the frequency of appearance of recombinants within three years of introduction from 100% to 14%, and delays their appearance by more than a year, on average. Cross-reactivity between parental and recombinant genotypes reduces the frequency of appearance to 36% and increases the probability of recombinant extinction following appearance from 0% to 83%. When a recombinant is cross-reactive with its parental types, its probability of extinction is influenced by cross-reactivity between the parental types in the opposite manner; that is, its probability of extinction after appearance decreases. Frequencies of P. falciparum outcrossing are mediated by frequencies of mixed-genotype infections in the host population, which are in turn mediated by the structure of cross-reactivity between parasite genotypes. The three leading hypotheses about how meiosis relates to oocyst production lead to quantitative, but no qualitative, differences in these results.

Alleles↗
PubMed2002

Evaluation of the OptiMAL rapid antigen test and species-specific PCR to detect placental Plasmodium falciparum infection at delivery.

During pregnancy, Plasmodium falciparum infection of the placenta frequently occurs in the absence of parasites in peripheral blood. We investigated the abilities of the OptiMAL rapid immunochromatographic strip test for P. falciparum lactate dehydrogenase and species-specific PCR performed on peripheral blood to detect placental infection or malaria-associated low birth weight. Of 509 Malawian women screened by microscopy, 76 had malaria infection. Among these 509 women, the frequency of peripheral blood parasitemia was low. The OptiMAL test gave positive results in 37 of 171 women tested (one of whom had placental but not peripheral blood parasitemia) and had sensitivities of 71% for peripheral parasitemia and 38% for placental parasitemia compared to the microscopy values. The specificity for peripheral parasitemia was 94%. In 135 women, PCR had sensitivities of 94% for peripheral blood malaria detected by microscopy and 72% for placental infection. In samples examined by PCR, the prevalence of malaria in peripheral blood increased from 26.7% by microscopy to 51.9%. Women with placental malaria and women with malaria in peripheral blood samples by microscopy or OptiMAL testing, but not women with malaria detected only by PCR, had lower-birth-weight babies than did women without malaria by these criteria. Positive results by PCR in the absence of microscopic parasitemia were not associated with low birth weight. Neither OptiMAL nor PCR testing of peripheral blood is adequately sensitive to detect all placental malaria infection, but a positive result by OptiMAL testing identifies women with a high proportion of low-birth-weight babies.

Adolescent↗
PubMed1996

Point mutations in the dihydrofolate reductase and dihydropteroate synthetase genes and in vitro susceptibility to pyrimethamine and cycloguanil of Plasmodium falciparum isolates from Papua New Guinea.

Plasmodium falciparum isolates from 24 Papua New Guinean patients with symptomatic malaria were tested for susceptibility to pyrimethamine and cycloguanil. Thirteen isolates were sensitive to both agents and the remainder exhibited varying degrees of resistance. No isolates were found to be resistant to one agent yet sensitive to the other and a positive correlation suggesting cross-resistance was found. Parasite DNA extracted from the patients' stained blood slides was amplified and sequenced to examine point mutations in the dihydrofolate reductase (DHFR) and dihydropteroate synthetase genes (DHPS) associated with antifolate resistance. All resistant isolates possessed mutations in the DHFR gene at codon 108, the majority changing from Ser to Asn, but one isolate from Ser to Thr, a change not previously reported in field isolates. A second mutation of the DHFR gene at Cys-59 to Arg was present in isolates with higher level resistance, but not exclusively so. Sequencing the DHPS gene, as a predictor of sulfadoxine resistance, revealed only one example that was different from DHPS alleles of sensitive isolates.

Animals↗
PubMed2002

In-vitro sensitivity of Plasmodium falciparum to chloroquine, halofantrine, mefloquine and quinine in Madagascar.

OBJECTIVE: To determine how sensitive Plasmodium falciparum is to the major antimalarial drugs in Madagascar. DESIGN: Assessment of Plasmodium falciparum isolates sensitivity to antimalarials, by use of the in-vitro radioisotope method. SETTING: Ankazobe and Saharevo in the foothill areas; and Toamasina and Tolagnaro in the coastal areas (between January 1998 and November 1999). SUBJECTS: Primary Plasmodium falciparum isolates from patients with uncomplicated malaria attack. RESULTS: Between January 1998 and November 1999, of the 293 in-vitro tests done with at least one antimalarial, 70% (205/293) were interpretable. As there was no significant difference between results from the four study sites, the data have been expressed as a whole. All of the successfully tested isolates were sensitive to halofantrine (n = 56) and to quinine (n = 199), 5.8% (12/205) of the isolates were resistant to chloroquine and 2% (4/199) to mefloquine. The geometric mean IC50 was 0.3 microg/L for halofantrine (95% CI = 0.1-0.4 microg/L); 9.4 microg/L for chloroquine (95% CI = 7.3-10.8 microg/L); 3.8 microg/L for mefloquine (95% CI = 3.3-4.3 microg/L); and 26.8 microg/L for quinine (95% CI = 24.3-29.4 microg/L). The low positive correlation found between halofantrine and chloroquine IC50s (n = 56; r = 0.41, P = 0.002) suggests a risk of cross-resistance between these two drugs. CONCLUSION: The degree and frequency of chloroquine resistance in-vitro is stationary in Madagascar compared to previous results during the last decade. The in-vitro sensitivity of P. falciparum to quinine, mefloquine and halofantrine encourages the use of these drugs as alternative in case of chloroquine treatment failure. Nevertheless, it is important to maintain and to extend malaria and drug sensitivity surveillance in Madagascar.

Animals↗
PubMed2003

Cross-binding between Plasmodium falciparum CTL epitopes and HLA class I molecules.

Plasmodium falciparum CTL epitope minigenes containing HLA-A2 and HLA-B7 subtype supermotifs were cloned into a plasmid expression vector; this expression was measured in eight human HLA class I molecule specific cell lines. Three assays for in vitro antigen presentation analysis were developed to examine the cross-binding between CTL epitopes and HLA class I molecules, including cell surface peptide-MHC class I binding assay, binding stabilization assay and MHC class I assembling assay. The results demonstrated that the HLA-B51 restricted CTL epitope of Plasmodium falciparum could be presented by other HLA class I molecules; however, no other presentation was found for HLA-A2.1 CTL epitope. This work suggests the possibility for improved vaccine-coverage rates by development of a CTL vaccine which contains epitopes capable of cross-binding among different MHC class I alleles.

Animals↗
PubMed2001

Human antibodies against Plasmodium falciparum liver-stage antigen 3 cross-react with Plasmodium yoelii preerythrocytic-stage epitopes and inhibit sporozoite invasion in vitro and in vivo.

The Plasmodium falciparum liver-stage antigen 3 (LSA3), a recently identified preerythrocytic antigen, induces protection against malaria in chimpanzees. Using antibodies from individuals with hyperimmunity to malaria affinity purified on recombinant or synthetic polypeptides of LSA3, we identified four non-cross-reactive B-cell epitopes in Plasmodium yoelii preerythrocytic stages. On sporozoites the P. yoelii protein detected has a molecular mass similar to that of LSA3. T-cell epitopes cross-reacting with P. yoelii were also demonstrated using peripheral blood lymphocytes from LSA3-immunized chimpanzees. In contrast, no cross-reactive epitopes were found in Plasmodium berghei. LSA3-specific human antibodies exerted up to 100% inhibition of in vitro invasion of P. yoelii sporozoites into mouse hepatocytes. This strong in vitro activity was reproduced in vivo by passive transfer of LSA3 antibodies. These results indicate that the homologous epitopes may be biologically functional and suggest that P. yoelii could be used as a model to assess the antisporozoite activity of anti-LSA3 antibodies.

Animals↗
PubMed2005

[Genetic diversity of Plasmodium falciparum and its implications in the epidemiology of malaria].

Genetic diversity provides Plasmodium falciparum with the potential capacity of avoiding the immune response, and possibly supporting the selection of drug or vaccine resistant parasites. These genetic characters play key roles in the selection of appropriate malaria control measures. Diverse clones of Plasmodium falciparum, often denoted as strains, has been documented, and the degree of genetic diversity supported by several kinds of PCR (polymerase chain reaction) assays. Many studies in different endemic regions with differences in their level of disease transmission have clarified the interactions between the parasite populations and malaria epidemiology. This paper describes recombination events of the malaria parasite life cycle that originate such genetic diversity in P. falciparum, reviewing different studies on this aspect and its implications in the immunity and development of control measures in regions with different degrees of endemicity.

Animals↗
PubMedDate not supplied

Genetic evidence that RI chloroquine resistance of Plasmodium falciparum is caused by recrudescence of resistant parasites.

Isolates of Plasmodium falciparum from patients in a Sudanese village exhibiting RI resistance to chloroquine have been typed for allelic variants of 2 merozoite surface antigens, MSP1 and MSP2. Blood forms were taken from each patient before chloroquine was administered, and after parasites had reappeared following treatment. Each patient was found to be infected with genetically different parasites. However, in each patient the parasites of the recrudescent infections possessed the same alleles of each gene as those of the primary infection. The results show that the parasites which reappeared after chloroquine were a genuine recrudescence of the primary forms, and not derived from a new infection.

Alleles↗
PubMed1999

Genotypes of merozoite surface protein 2 of Plasmodium falciparum in Tanzania.

The merozoite surface protein 2 (MSP2) of Plasmodium falciparum is extremely polymorphic: 82 different msp2 alleles were found in 4 studies of molecular epidemiology conducted in Tanzania. This diversity renders msp2 suitable as a marker gene for the genotyping of P. falciparum infections. Amplification of msp2 by the polymerase chain reaction (PCR), and subsequent restriction digests of the PCR product (PCR-restriction fragment length polymorphism genotyping), has proved to be an informative tool for enumerating multiple concurrent infections in a blood sample, and distinguishing individual alleles. Depending on the specific questions asked in a genotyping study, analytical techniques of different degrees of complexity are employed. The restriction fragments resulting from a single HinfI digest generally allow the enumeration of multiple concurrent infections and the determination of their allelic families. When a restriction pattern is too complex to be resolved, owing to the high number of concurrent infections, or due to the appearance of previously undescribed alleles, one or more additional digests (DdeI, RsaI, ScrfI) may be necessary. To determine individual alleles unequivocally, in particular in longitudinal studies, when several consecutive samples need to be compared with each other, a more detailed analysis involving all 3 additional digests is applied. The methodological experience and results gained in 4 epidemiological field studies involving msp2 genotyping are summarized. We also provide the HinfI restriction patterns and some nucleotide sequences of the alleles found so far in our studies in Tanzania.

Alleles↗
PubMed2001

Use of variability in the stage-specific transcription levels of Plasmodium falciparum in the selection of target genes.

The malarial parasite Plasmodium falciparum exhibits several morphological and developmental stages. We have quantified the level of expression of a battery of genes in the ring and trophozoite stage-two of the most prominent stages in the erythrocytic development of the parasite. Using optimized RT-PCR, we observed that some of the genes show a large variation in stage-specific expression. We have also correlated the level of mRNA expression (of the target enzyme) to its metabolic requirement using specific inhibitors. This protocol gives us a handle to identify vulnerable target genes that could be used to develop antimalarials.

Animals↗
PubMed2004

Geographical and temporal conservation of antibody recognition of Plasmodium falciparum variant surface antigens.

The slow acquisition of protection against Plasmodium falciparum malaria probably reflects the extensive diversity of important antigens. The variant surface antigens (VSA) that mediate parasite adhesion to a range of host molecules are regarded as important targets of acquired protective immunity, but their diversity makes them questionable vaccine candidates. We determined levels of VSA-specific immunoglobulin G (IgG) in human plasma collected at four geographically distant and epidemiologically distinct localities with specificity for VSA expressed by P. falciparum isolates from three African countries. Plasma levels of VSA-specific IgG recognizing individual parasite isolates depended on the transmission intensity at the site of plasma collection but were largely independent of the geographical origin of the parasites. The total repertoire of immunologically distinct VSA thus appears to be finite and geographically conserved, most likely due to functional constraints. Furthermore, plasma samples frequently had high IgG reactivity to VSA expressed by parasites isolated more than 10 years later, showing that the repertoire is also temporally stable. Parasites from patients with severe malaria expressed VSA (VSASM) that were better recognized by plasma IgG than VSA expressed by other parasites, but importantly, VSASM-type antigens also appeared to show substantial antigenic homogeneity. Our finding that the repertoire of immunologically distinct VSA in general, and in particular that of VSASM, is geographically and temporally conserved raises hopes for the feasibility of developing VSA-based vaccines specifically designed to accelerate naturally acquired immunity, thereby enhancing protection against severe and life-threatening P. falciparum malaria.

Africa, Eastern↗
PubMed1992

Dynamics of multi-drug resistance in Plasmodium falciparum in Thailand.

Since the initial report of resistance of Plasmodium falciparum to chloroquine in 1960 in the Thai-Cambodian border resistance to alternative drugs occurred early after their introduction. This development is considered to be the result of population migration and excessive drug pressure along with the presence of a multi-resistance gene within the parasite population. Multi-resistant strains as such have been disseminated throughout the country by returning migrant populations.

Animals↗
PubMedDate not supplied

[Parasitological resistance of Plasmodium falciparum to antimalarial drugs: what physicians should keep in mind].

Plasmodium falciparum drug resistance has considerably modified the attitude of physicians in terms of malaria case management. However, a bad understanding of the resistance phenomenon can lead to non-appropriate therapeutic and/or public health practices. The objective of this paper was to contribute to clarify the concept of parasitological resistance by analysing the different types of resistance observed in vivo. We showed through some examples that the precision of in vivo parasitological results depends on the type of microscopical technique used. We also showed that the classification system into resistance levels RI, RII, and RIII does not correspond to an increase in the resistance of the parasite itself but rather to an increase in the proportion of the resistant strains compared to the sensitive ones circulating in a given population. Mutant strains are circulating in low proportions as long as there is no selective drug pressure. They can be first detected in vitro and, later on, when their proportion increase, they are detected in vivo, first in non-immune subjects and later in semi-immune subjects. Therefore, the role of the host immunity is important in malaria drug resistance. To conclude, increasing use of antimalarial drugs (especially in monotherapy) cannot thwart the resistance, but rather leads to the selection of mutants strains. As the proportion of the mutant strains increases compared to the sensitive (wild) ones, it will reach the microscopic detection level and then, the clinical level. It is important that physicians involved in malaria case management understand these notions in order to avoid non-appropriate therapeutic decisions.

Animals↗
PubMed1992

Recognition of Plasmodium falciparum asexual stage antigens by antibodies in sera from people exposed to Plasmodium vivax.

An analysis of Plasmodium falciparum antigen-specific antibodies was performed on 44 serum samples from Guatemala, a region endemic for P. vivax. Most sera showed positive reactivity to P. falciparum asexual stage antigens by indirect immunofluorescent assay, enzyme-linked immunosorbent assay, and immunoprecipitation analysis using biosynthetically labeled parasites. Although several antigens were recognized by these sera, proteins with molecular weights of 195 kD, 140 kD, and in the range of 70-80 kD were strongly recognized by many of the sera studied. No such reactivity was observed for any of the surface antigens in the male and female gametes and zygotes of P. falciparum. These studies suggest that P. vivax and P. falciparum, two major human parasites, may share certain epitopes in several antigens of immunologic significance.

Adolescent↗
PubMed2003

Human migration, mosquitoes and the evolution of Plasmodium falciparum.

To date, coalescent analysis of the Plasmodium falciparum genome sequence has failed to provide a unifying theory regarding the parasite's evolution. While a better understanding of the evolution of the malaria genome will undoubtedly clarify the current controversy, the importance of the parasite's interplay with both the human host and mosquito vector cannot be underestimated. Changes in the population biology or ecology of either one of these species have consequences for malaria transmission and this was never more apparent than in the environmental changes brought about by the advent of agriculture.

Agriculture↗
PubMed2000

Transcriptional mapping and RNA processing of the Plasmodium falciparum mitochondrial mRNAs.

The mitochondrial genome of Plasmodium falciparum encodes three protein coding genes and highly fragmented rRNAs. The genome is polycistronically transcribed and, since gene-size transcripts are much more abundant than the polycistronic transcripts, the latter are presumably cleaved to produce the smaller, mature mRNAs and rRNAs. Mapping the transcripts of the P. falciparum mitochondrial protein coding genes shows that the 3' end of each gene directly abuts the 5' end of the gene located immediately downstream. The 5' ends of the protein coding genes are also closely apposed to adjacent genes, with one directly abutting a gene on the same DNA strand and two others separated by just 13 nt from an rDNA fragment encoded on the opposite strand. These mapping data are consistent with production of the mRNAs by cleavage from a polycistronic precursor transcript. Further processing of the mRNAs comes from addition of oligo(A) tails. Unexpectedly, the presence and length of such tails varies in a gene-specific fashion. In this regard, polyadenylation of the P. falciparum mitochondrial mRNAs is more similar to that seen for the P. falciparum mitochondrial rRNAs than that of mitochondrial mRNAs in other organisms.

Amino Acid Sequence↗
PubMed2002

Prospective assessment of a new polymerase chain reaction target (STEVOR) for imported Plasmodium falciparum malaria.

The diagnostic value of a polymerase chain reaction (PCR)-based method for amplifying a new target of repeated genes (STEVOR) in Plasmodium falciparum was prospectively assessed on samples from 210 febrile patients returning from areas endemic for malaria. This method is capable of detecting 0.01 parasites in one microliter of blood. Plasmodium falciparum STEVOR PCR confirmed the results of the thin- and thick-film direct examination method but identified Plasmodium falciparum in four patients in whom direct examination was inconclusive at the species level. Moreover, PCR was positive in two patients with a negative direct examination. Thus, Plasmodium falciparum STEVOR PCR had 100% sensitivity and specificity and could be used in selected parasitology laboratories when expert advice is required.

Animals↗
PubMedDate not supplied

A field trial of the ParaSight-F test for the diagnosis of Plasmodium falciparum infection.

The rapid manual ParaSight-F test for Plasmodium falciparum is an antigen capture test detecting trophozoite-derived histidine rich protein II, is simple and provides a definitive diagnosis within 10 min. Compared with 913 thick blood film examinations, the ParaSight-F test had 93.4% sensitivity and 98.2% specificity. Compared with 520 blood samples within the same study examined with the aid of the polymerase chain reaction, the ParaSight-F test had 91.6% sensitivity and 99.4% specificity. The ParaSight-F test could be a valuable diagnostic tool for falciparum malaria in any situation requiring rapid diagnosis in the absence of microscopical examination.

Animals↗