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At least 109 records · Page 6Linked to original sources
PubMed1997

Multiple antigen constructs (MACs): induction of sterile immunity against sporozoite stage of rodent malaria parasites, Plasmodium berghei and Plasmodium yoelii.

We prepared multiple antigen constructs (MACs) using circumsporozoite (CS) protein-based B-epitopes from Plasmodium berghei, (PPPPNPND)2 and Plasmodium yoelii, (QGPGAP)3QG, along with a P. berghei T-helper epitope KQIRDSITEEWS. Mice were immunized with individual MACs in oil-in-water or water-in-oil vehicles containing block copolymer (P1005) and detoxified RaLPS (RaLPS) as well as other adjuvants. Sporozoite challenge results demonstrated that MACs in adjuvant could induce antibodies capable of active and passive protection. Water-in-oil vaccines induced the highest level of protection in mice immunized with either P. berghei or P. yoelii MACs. In a study aimed at co-eliciting immunity against P. berghei and P. yoelii, three immunizations with MACs induced protective antibodies against P. berghei but not P. yoelii parasite challenge. Therefore, it can be concluded that individually MACs are capable of inducing strong and protective immune responses to either species of rodent malaria, and that protection can be passively transferred. When MAC formulations were used together as a combined vaccine, P. berghei MACs induced a strong protective antibody response while P. yoelii MACs induced a weaker nonprotective response.

Animals↗
PubMed2003

A multiplex polymerase chain reaction for a differential diagnosis of Plasmodium falciparum and Plasmodium vivax.

A multiplex PCR was designed for the differential diagnosis of the two parasite species by targeting the 18S rRNA gene with a set of primer combinations, amplifying DNA fragments of 1451-bp and 833-bp for P. falciparum and P. vivax, respectively. The sensitivity of this PCR test was high, as minimal as 0.1 parasite per one microliter of blood sample and a minimum of four copies of the target gene could be detected. For the diagnosis of mixed infection of two Plasmodium spp., there were no apparent competition or cross-reaction between the majority and minority Plasmodium species. The multiplex PCR was evaluated on 210 clinical samples and 60 normal controls. The PCR test yielded highly concordant results with microscopic examination, with the only one exception of a mixed (P. falciparum plus P. vivax) infection case, which was diagnosed as a single infection of P. falciparum by microscopy. We propose that the multiplex PCR is a sensitive, specific, and rapid tool that can serve as a useful differential diagnostic tool for detecting P. falciparum and P. vivax.

Animals↗
PubMedDate not supplied

Plants as sources of antimalarial drugs, Part 4: Activity of Brucea javanica fruits against chloroquine-resistant Plasmodium falciparum in vitro and against Plasmodium berghei in vivo.

Extracts of Brucea javanica fruit have been prepared and monitored for their in vitro and in vivo antiplasmodial activities. The antimalarial activity of the fruit was found to be attributable to its quassinoid constituents. Nine of the quassinoids possessed in vitro IC50 values between 0.046-0.0008 microgram/ml against the chloroquine resistant Plasmodium falciparum strain (Kl) tested. The two quassinoid glycosides tested were considerably less active in vitro than the aglycones. Four quassinoids were found to possess activity in vivo against Plasmodium berghei infections in mice after oral dosing. All five quassinoids tested in vivo showed some toxicity.

Animals↗
PubMed2001

Anti-mosquito midgut antibodies block development of Plasmodium falciparum and Plasmodium vivax in multiple species of Anopheles mosquitoes and reduce vector fecundity and survivorship.

The mosquito midgut plays a central role in the sporogonic development of malaria parasites. We have found that polyclonal sera, produced against mosquito midguts, blocked the passage of Plasmodium falciparum ookinetes across the midgut, leading to a significant reduction of infections in mosquitoes. Anti-midgut mAbs were produced that display broad-spectrum activity, blocking parasite development of both P. falciparum and Plasmodium vivax parasites in five different species of mosquitoes. In addition to their parasite transmission-blocking activity, these mAbs also reduced mosquito survivorship and fecundity. These results reveal that mosquito midgut-based antibodies have the potential to reduce malaria transmission in a synergistic manner by lowering both vector competence, through transmission-blocking effects on parasite development, and vector abundance, by decreasing mosquito survivorship and egg laying capacity. Because the intervention can block transmission of different malaria parasite species in various species of mosquitoes, vaccines against such midgut receptors may block malaria transmission worldwide.

Animals↗
PubMed1994

Life-spans of human T-cell responses to determinants from the circumsporozoite proteins of Plasmodium falciparum and Plasmodium vivax.

The longevity of specific human memory T-cell responses is largely unknown. However, a knowledge of the duration of memory is important for understanding immunity to an organism and for planning vaccine intervention. To address this, we have examined T-cell memory to malaria by determining T-cell responses by subjects recently exposed to peptides spanning the circumsporozoite (CS) proteins of two species of malaria-causing organisms, Plasmodium falciparum and Plasmodium vivax. Responses to vivax CS peptides by exposed Thai subjects were more frequent than responses by nonexposed individuals, permitting identification of determinants seen by vivax-induced responses. At the population level, there appears to be life-long memory, as the time since individuals were exposed did not diminish responsiveness to these determinants. In contrast, falciparum-exposed subjects were largely indistinguishable from nonexposed controls in responsiveness to falciparum CS determinants. However, a single peptide (F16: DNEKLRKPKHKKLKQPGDGN) was recognized significantly more frequently by P. falciparum-exposed than nonexposed Thai subjects. T cells responsive to this peptide were CD450+ and produced gamma-interferon. In contrast to the response to the vivax determinants and the other falciparum determinants, responsiveness to F16 was undetectable or minimal 2 years after exposure. Our data provide the average life-spans of certain malaria-specific T cells and are consistent with, but do not prove, the hypothesis that antigenic persistence (in the form of P. vivax hypnozoites) correlates with persistence of human T-cell memory.

Adult↗
PubMed1998

Precise timing of expression of a Plasmodium falciparum-derived transgene in Plasmodium berghei is a critical determinant of subsequent subcellular localization.

The development of transfection technology for malaria parasites holds significant promise for a more detailed characterization of molecules targeted by vaccines or drugs. One asexual blood stage vaccine candidate, apical membrane antigen-1 (AMA-1) of merozoite rhoptries has been shown to be the target of inhibitory, protective antibodies in both in vitro and in vivo studies. We have investigated heterologous (trans-species) expression of the human malaria Plasmodium falciparum AMA-1 (PF83/AMA-1) in the rodent parasite Plasmodium berghei. Transfected P. berghei expressed correctly folded and processed PF83/AMA-1 under control of both pb66/ama-1 and dhfr-ts promoters. Timing of expression was highly promoter-dependent and was critical for subsequent subcellular localization. Under control of pb66/ama-1, PF83/AMA-1 expression and localization in P. berghei was limited to the rhoptries of mature schizonts, similar to that observed for PF83/AMA-1 in P. falciparum. In contrast the dhfr-ts promoter permitted PF83/AMA-1 expression throughout schizogony as well as in gametocytes and gametes. Localization was aberrant and included direct expression at the merozoite and gamete surface. Processing from the full-length 83-kDa protein to a 66-kDa protein was observed not only in schizonts but also in gametocytes, indicating that processing could be mediated outside of rhoptries by a common protease. Trans-species expressed PF83/AMA-1 was highly immunogenic in mice, resulting in a response against a functionally critical domain of the molecule.

Animals↗
PubMed1977

Evidence for differences in erythrocyte surface receptors for the malarial parasites, Plasmodium falciparum and Plasmodium knowlesi.

Human erythrocytes lacking various blood group determinants were susceptible to invasion by Plasmodium falciparum including Duffy-negative erythrocytes that are refractory to invasion by Plasmodium knowlesi. Erythrocytes treated with trypsin or neuraminidase had reduced susceptibility of P. falciparum and normal susceptibility to P. knowlesi. Chymotrypsin treatment (0.1 mg/ml) blocked invasion only by P. knowlesi. The differential effect of enzymatic cleavage of determinats from the erythrocyte surface on invasion by these parasites suggests that P. falciparum and P. knowlesi interact with different determinants on the erythrocyte surface.

Chymotrypsin↗
PubMed1982

Circumsporozoite proteins of human malaria parasites Plasmodium falciparum and Plasmodium vivax.

Monoclonal antibodies were raised against sporozoites of two species of malaria parasites, Plasmodium falciparum and Plasmodium vivax. The antibodies reacted with polypeptides (circumsporozoite proteins) that are uniformly distributed over the entire surface of sporozoites, as shown by indirect immunofluorescence and by the circumsporozoite precipitin reaction. The epitopes recognized by the monoclonal antibodies were expressed on sporozoites from different geographical isolates of the homologous species but were not detected on sporozoites of heterologous species nor on blood forms of the parasite. The monoclonal antibody to P. falciparum specifically immunoprecipitated two polypeptides of apparent 67,000 mol wt (Pf67) and 58,000 mol wt (Pf58) from extracts of [35S]methionine-labeled P. falciparum sporozoites. Similarly, the anti-P. vivax monoclonal immunoprecipitated two proteins of 51,000 mol wt (Pv51) and 45,000 mol wt (Pv45) from extracts of metabolically labeled P. vivax sporozoites. The extracts were also reacted with the serum of human volunteers successfully vaccinated with sporozoites of either P. vivax or P. falciparum. The patterns of immunoprecipitation were almost identical to those obtained with the corresponding monoclonal antibodies. The circumsporozoite proteins of P. falciparum and P. vivax play a role in immune protection. Incubation of the appropriate monoclonal antibody with viable sporozoites of the homologous species significantly reduced parasite infectivity, as determined by sporozoite neutralization assays carried out in splenectomized chimpanzees.

Animals↗
PubMed2002

Randomized, placebo-controlled trial of atovaquone/proguanil for the prevention of Plasmodium falciparum or Plasmodium vivax malaria among migrants to Papua, Indonesia.

The increasing prevalence of resistance to antimalarial drugs reduces options for malaria prophylaxis. Atovaquone/proguanil (Malarone; GlaxoSmithKline) has been >95% effective in preventing Plasmodium falciparum malaria in lifelong residents of areas of holoendemicity, but data from persons without clinical immunity or who are at risk for Plasmodium vivax malaria have not been described. We conducted a randomized, double-blinded study involving 297 people from areas of nonendemicity in Indonesia who migrated to Papua (where malaria is endemic) < or =26 months before the study period. Subjects received prophylaxis with 1 Malarone tablet (250 mg of atovaquone and 100 mg of proguanil hydrochloride; n=148) or placebo (n=149) per day for 20 weeks. Hematologic and clinical chemistry values did not change significantly. The protective efficacy of atovaquone/proguanil was 84% (95% confidence interval [CI], 44%-95%) for P. vivax malaria, 96% (95% CI, 72%-99%) for P. falciparum malaria, and 93% (95% CI, 77%-98%) overall. Atovaquone/proguanil was well tolerated, safe, and effective for the prevention of drug-resistant P. vivax and P. falciparum malaria in individuals without prior malaria exposure who migrated to Papua, Indonesia.

Adolescent↗
PubMed1993

Mice immunized with a synthetic peptide construct corresponding to an epitope present on a Plasmodium falciparum antigen are protected against Plasmodium chabaudi challenge.

Inhibitory monoclonal antibody (MoAb) 8E7/55 recognizes a parasitophorous vacuole membrane (PVM) antigen in Plasmodium falciparum. Previous studies have identified the epitope, DNNLVSGP, recognized by the MoAb. A synthetic peptide containing this sequence was synthesized and coupled to diphtheria toxoid (DT) and was found capable of generating antibodies when used as an immunogen in mice which recognize the native antigen exp-1. In this study we demonstrate the ability of the MoAb and antisera generated against the peptide construct to recognize a 54 kD PVM antigen in Plasmodium chabaudi. The P. chabaudi antigen is synthesized in trophozoites and released to the surrounding culture media outside the parasitized erythrocyte. Mice immunized with the peptide conjugate are protected when challenged with a lethal strain of P. chabaudi. Protection in the mice correlated with the antibody titre prior to challenge. If the PVM antigen from P. chabaudi is a homologue of exp-1 from P. falciparum, then these experiments may provide a guide to the antibody titres required in human trials before antibody mediated protection could be expected. The discovery that a PVM localized antigen is secreted into the surrounding in vitro culture media provides us with a valuable model system for further investigation of protein trafficking pathways in malaria-infected erythrocytes.

Amino Acid Sequence↗
PubMed2005

Motility and infectivity of Plasmodium berghei sporozoites expressing avian Plasmodium gallinaceum circumsporozoite protein.

Avian and rodent malaria sporozoites selectively invade different vertebrate cell types, namely macrophages and hepatocytes, and develop in distantly related vector species. To investigate the role of the circumsporozoite (CS) protein in determining parasite survival in different vector species and vertebrate host cell types, we replaced the endogenous CS protein gene of the rodent malaria parasite Plasmodium berghei with that of the avian parasite P. gallinaceum and control rodent parasite P. yoelii. In anopheline mosquitoes, P. berghei parasites carrying P. gallinaceum and rodent parasite P. yoelii CS protein gene developed into oocysts and sporozoites. Plasmodium gallinaceum CS expressing transgenic sporozoites, although motile, failed to invade mosquito salivary glands and to infect mice, which suggests that motility alone is not sufficient for invasion. Notably, a percentage of infected Anopheles stephensi mosquitoes showed melanotic encapsulation of late stage oocysts. This was not observed in control infections or in A. gambiae infections. These findings shed new light on the role of the CS protein in the interaction of the parasite with both the mosquito vector and the rodent host.

Animals↗
PubMedDate not supplied

Common epitopes in the circumsporozoite proteins of Plasmodium berghei and Plasmodium gallinaceum identified by monoclonal antibodies to the P. gallinaceum circumsporozoite protein.

Monoclonal antibodies that react with the circumsporozoite protein of the avian malaria Plasmodium gallinaceum sporozoites also reacted with circumsporozoite protein of the rodent malaria Plasmodium berghei. Two types of reactivity were identified: 1) two monoclonal antibodies reacted with P. berghei sporozoite protein by enzyme-linked immunosorbent assay, Western blot and indirect immunofluorescence antibody, 2) six other monoclonal antibodies reacted with P. berghei sporozoites by ELISA and Western blot only. We studied whether these differences could be explained by reactivity in enzyme-linked immunosorbent assay with different P. berghei circumsporozoite peptides. Although all P. gallinaceum monoclonal antibodies reacted with the P. berghei repeats, the first group reacted with a conserved peptide sequence, N1, whereas the second group did not. These results suggest that circumsporozoite proteins from P. gallinaceum and P. berghei share common epitopes. The biological significance of our finding is not yet clear. Indeed, the cross-reactive monoclonal antibodies giving a positive indirect immunofluorescence antibody with the P. berghei sporozoites only caused a borderline effect on the living P. berghei parasites in vitro as measured by inhibition of sporozoite infectivity.

Amino Acid Sequence↗
PubMedDate not supplied

Mixed Plasmodium falciparum-Plasmodium malariae infection and hemoglobin SC disease: a case report.

In today's society, immigration and travel has resulted in large-scale population movements. This poses an additional challenge to the clinician when he or she takes the patient's history. The differential diagnosis of any presentation would need to include any diseases endemic to the area where the patient had been in. Ghana is considered a holoendemic high-risk area for the transmission of malaria. Moreover, compound heterozygous inheritance of hemoglobin (Hb) S and HbC often occurs in this area. We present a case of mixed Plasmodium falciparum-Plasmodium malariae infection complicating HbSC disease in a 34-year-old Ghanaian immigrant. We postulate that the malaria infection has transformed the patient's silent combined hemoglobinopathies (HbS/HbC) into a syndrome resembling a sickle cell crisis.

Adult↗
PubMed2006

Evaluation of the activities of pyrimethamine analogs against Plasmodium vivax and Plasmodium falciparum dihydrofolate reductase-thymidylate synthase using in vitro enzyme inhibition and bacterial complementation assays.

Pyrimethamine analogs were examined as potential agents against vivax malaria using a bacterial surrogate system carrying Plasmodium vivax dihydrofolate reductase-thymidylate synthase (PvDHFR-TS), in which the PvDHFR complemented chemically knocked out host dihydrofolate reductase. The system was initially tested with P. falciparum dihydrofolate reductase-thymidylate synthase and was found to have good correlation with the parasite-based system. The 50% inhibitory concentrations derived from PvDHFR-TS-dependent bacteria were correlated with their corresponding inhibition constants (Ki) from an enzyme inhibition assay, pointing to the likelihood that the potent enzyme inhibitors will also have potent antimalarial activities. Active compounds against both wild-type and S58R S117N (SP21) double-mutant P. vivax include analogs with structures which can avert a steric clash with the asparagine (S117N) side chain of the mutant, similar to those found for homologous Plasmodium falciparum mutants, raising the possibility that the same compounds can be developed against both types of antifolate-resistant malaria. This rapid and convenient drug screening system should be useful for development of new antifolates against P. vivax, for which a continuous culture system is not yet available.

Animals↗
PubMed1984

Role of macrophages in malaria: O2 metabolite production and phagocytosis by splenic macrophages during lethal Plasmodium berghei and self-limiting Plasmodium yoelii infection in mice.

The role of splenic macrophages in resistance to lethal Plasmodium berghei or self-limiting Plasmodium yoelii was studied by testing their rate of phagocytosis and their production of O2 metabolites (H2O2 and O2-) upon nonspecific stimulation with zymosan. It was found that, compared with P. berghei, infection of mice with P. yoelii resulted in an earlier appearance and in higher numbers of adherent cells in the spleen. Furthermore, the capacity of macrophages to generate O2 metabolites was significantly higher in P. yoelii- than in P. berghei-infected mice. This difference in the production of O2 metabolites was more pronounced when calculated on a per spleen basis. On the other hand, phagocytosis by macrophages was similar in both types of infection. The data suggest that lethal and nonlethal malaria species differ in their capacity to induce the production of O2 metabolites by macrophages, thereby influencing the final course of disease.

Animals↗
PubMed1985

Monoclonal antibodies produced against sporozoites of the human parasite Plasmodium malariae abolish infectivity of sporozoites of the simian parasite Plasmodium brasilianum.

We have used a sporozoite neutralization assay to define the biological relevance of the cross-reactivity of two monoclonal antibodies, raised against sporozoites of the human parasite Plasmodium malariae (Uganda 1/CDC), with sporozoites of the simian parasite Plasmodium brasilianum (Colombian). In vitro incubation of each of these two monoclonal antibodies with sporozoites of P. brasilianum totally abolished the infectivity of these parasites for Saimiri sciureus. Using Western blot analysis and one of the P. malariae monoclonal antibodies, we identified two sporozoite proteins characteristic of the Colombian isolate of P. brasilianum with apparent molecular weights of 56,000 and 66,000. The same monoclonal antibody identified two proteins in an extract of the Peruvian isolate of P. brasilianum with apparent molecular weights of 59,000 and 69,000.

Animals↗