Blood loss and replacement in plasmodial infections. III. Plasmodium cynomolgi, Plasmodium gonderi and Plasmodium knowlesi in Macaca mulatta mulatta, the rhesus monkey.
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Animals↗
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[Studies of the duration of the course of Plasmodium vivax, Plasmodium falciparum and Plasmodium malariae infections].
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Humans↗
Observations on the pre-erythrocytic stages of Plasmodium relictum, Plasmodium cathemerium, and Plasmodium gallinaceum in various birds.
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Animals↗
[Cross serological reactions between Plasmodium falciparum and Plasmodium cynomolgi Bastianellii. Application to the serodiagnosis, by immunofluorescence, of human Plasmodium falciparum malaria].
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Adolescent↗
Quantitative cytochemistry of malaria infected erythrocytes (Plasmodium berghei, Plasmodium chabaudi and Plasmodium vinckei).
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Cytodiagnosis↗
[Comparative analysis at the nucleotide level of the genes encoding the lactate dehydrogenase enzyme of Plasmodium vivax and Plasmodium falciparum.].
In this study, the nucleotide sequence of the enzyme lactate dehydrogenase from Plasmodium vivax has been compared to the same enzyme from another malaria parasite Plasmodium falciparum. It was found that the identity between two sequences was 74.8%. The percentage of the GC value was found to be higher in the Plasmodium vivax lactate dehydrogenase (46.6%) than in that of Plasmodium falciparum (33%). The nucleotide sequence that corresponds to the 5 amino acid insertion in Plasmodium lactate dehydrogenase is also present in Plasmodium vivax. This site will be targeted in the design of novel antimalarials for Plasmodium vivax as has been for Plasmodium falciparum.
English Abstract↗
Plasmodium inui is not closely related to other quartan Plasmodium species.
Plasmodium inui (Halberstaedter and von Prowazek, 1907), a malarial parasite of Old World monkeys that occurs in isolated pockets throughout the Celebes, Indonesia, Malaysia, and the Philippines, has traditionally been considered to be related more closely to Plasmodium malariae of humans (and its primate counterpart Plasmodium brasilianum), than to other primate Plasmodium species. This inference was made in part because of the similarities in the periodicities or duration of the asexual cycle in the blood, the extended sporogonic cycle, and the longer period of time for development of the pre-erythrocytic stages in the liver. Both P. inui and P. malariae have quartan (72 hr) periodicities associated with their asexual cycle, whereas other primate malarias, such as Plasmodium fragile and Plasmodium cynomolgi, are associated with tertian periodicities (48 hr), and Plasmodiumn knowlesi, with a quotidian (24 hr) periodicity. Phylogenetic analyses of portions of orthologous small subunit ribosomal genes reveal that P. inui is actually more closely related to the Plasmodium species of the "vivax-type" lineage than to P. malariae. Ribosomal sequence analysis of many different, geographically isolated, antigenically distinct P. inui isolates reveals that the isolates are nearly identical in sequence and thus members of the same species.
Animals↗
Rapid immunochromatographic malarial antigen detection unreliable for detecting Plasmodium malariae and Plasmodium ovale.
In order to determine the reliability of two commercial tests for the rapid detection of plasmodial antigen in cases of infection with Plasmodium ovale and Plasmodium malariae, the products were evaluated in four centers and a search of the relevant literature was performed. The results of the present and previous studies were compared. With overall sensitivities ranging between 18.8% and 47.6% for Plasmodium malariae and between 20% and 31.3% for Plasmodium ovale, it is evident that neither test is reliable for the detection of Plasmodium ovale and Plasmodium malariae infections.
Animals↗
Plasmodium vivax polymorphs and Plasmodium falciparum circumsporozoite proteins in Anopheles (Diptera: Culicidae) from Belize, Central America.
Eight species of Anopheles mosquitoes from indoor/outdoor human landing collections in Belize, Central America, were examined for human Plasmodium circumsporozoite protein (CSP) using an enzyme-linked immunosorbent assay (ELISA). A total of 14 of 9,104 females tested were positive from general surveys throughout Belize and three of 11,966 were positive from a longitudinal study in Caledonia, northern Belize. ELISA results, using pooled head-thorax preparations and species-specific monoclonal antibodies directed against the circumsporozoite proteins of Plasmodium falciparum and two Plasmodium vivax polymorphs (210 and VK247), found four species reactive: Anopheles vestitipennis (3 pools), Anopheles darlingi (2 pools), Anopheles albimanus (10 pools), and Anopheles gabaldoni (2 pools). The minimum field infection rates (MFIR) for combined Plasmodium species from the general survey were 0.282% for An. vestitipennis, 0.271% for An. darlingi, 0.126% for An. albimanus, and 0.395% for An. gabaldoni. MFIRs for combined Plasmodium species from the longitudinal study in the village of Caledonia were 0.018% for both An. vestitipennis and An. albimanus and 1.66% for An. gabaldoni. Positive CSP pools were collected from the Cayo, Corozal, Orange Walk, Stann Creek, and Toledo political districts. No CSP positive pools were detected from collections in the Belize District. The study provides valuable information on the spatial distribution and species type of Plasmodium positive mosquitoes. This information, in combination with other vector data, suggest that An. vestitipennis and An. darlingi are commonly involved in malaria transmission. Additionally, these species appear to be much more efficient vectors than An. albimanus in Belize.
Animals↗
Hepatocyte CD81 is required for Plasmodium falciparum and Plasmodium yoelii sporozoite infectivity.
Plasmodium sporozoites are transmitted through the bite of infected mosquitoes and first invade the liver of the mammalian host, as an obligatory step of the life cycle of the malaria parasite. Within hepatocytes, Plasmodium sporozoites reside in a membrane-bound vacuole, where they differentiate into exoerythrocytic forms and merozoites that subsequently infect erythrocytes and cause the malaria disease. Plasmodium sporozoite targeting to the liver is mediated by the specific binding of major sporozoite surface proteins, the circumsporozoite protein and the thrombospondin-related anonymous protein, to glycosaminoglycans on the hepatocyte surface. Still, the molecular mechanisms underlying sporozoite entry and differentiation within hepatocytes are largely unknown. Here we show that the tetraspanin CD81, a putative receptor for hepatitis C virus, is required on hepatocytes for human Plasmodium falciparum and rodent Plasmodium yoelii sporozoite infectivity. P. yoelii sporozoites fail to infect CD81-deficient mouse hepatocytes, in vivo and in vitro, and antibodies against mouse and human CD81 inhibit in vitro the hepatic development of P. yoelii and P. falciparum, respectively. We further demonstrate that the requirement for CD81 is linked to sporozoite entry into hepatocytes by formation of a parasitophorous vacuole, which is essential for parasite differentiation into exoerythrocytic forms.
Animals↗
Monoclonal antibody identifies circumsporozoite protein of Plasmodium malariae and detects a common epitope on Plasmodium brasilianum sporozoites.
We produced a hybridoma secreting an immunoglobulin G1 monoclonal antibody against the circumsporozoite protein of the human malaria parasite Plasmodium malariae (Uganda 1/CDC). The monoclonal antibody produces a circumsporozoite precipitation reaction when incubated with viable sporozoites of P. malariae and reacts at high titers with heat-fixed sporozoites in an indirect immunofluorescent antibody test. Using the purified monoclonal antibody and Western blot analysis, we identified two polypeptides with apparent molecular weights of 60,000 (Pm 60) and 48,000 (Pm 48) in extracts of P. malariae sporozoites. Two-dimensional electrophoretic analysis of Pm 60 and the circumsporozoite protein Pm 48 indicated their isoelectric points to be acidic, with values of 5.3 and 4.7 to 5.0, respectively. A two-site immunoradiometric assay showed that the circumsporozoite protein recognized by the monoclonal antibody contains a repetitive epitope. P. malariae monoclonal antibody also reacted strongly with sporozoites of the simian parasite Plasmodium brasilianum, indicating a shared epitope on sporozoites of the two species. The P. malariae antibody did not bind sporozoite antigens of any other primate malarias, including Plasmodium falciparum, Plasmodium vivax, and Plasmodium ovale.
Animals↗
Complete nucleotide sequences of the mitochondrial genomes of two avian malaria protozoa, Plasmodium gallinaceum and Plasmodium juxtanucleare.
We analyzed mitochondrial genomes of two avian malaria protozoa, Plasmodium gallinaceum and Plasmodium juxtanucleare. Both mitochondrial genomes were estimated to be 6,002 and 6,014 bp in length, respectively, and to have the identical gene organization and contents to that of other Plasmodium species previously analyzed; three functional genes for cytochrome c oxidase subunit I, III, and cytochrome (cyt b), with following sets of discontinuous and scrambled 15 ribosomal subunit RNA (rRNA) genes. Similarities of the three protein-coding genes showed closer relationship within avian malaria protozoa rather than mammalian Plasmodium species. In addition, we showed the tandem repeated structure of each mitochondrial genome of both P. gallinaceum and P. juxtanucleare as well as previously found in mammalian Plasmodium species. This study revealed the complete sequences and structure of the mitochondrial genomes of avian malaria protozoa for the first time.
Animals↗
[A new Plasmodium species from a lemur: Plasmodium coulangesi n. sp].
The splenectomy of a female Lemur macaco macaco, showing a scanty blood infection by Haemosporidians and a Trypanosome was followed by a dramatic increase of the rate of intra-erythrocytic parasitaemia. Three species of Plasmodium where then identified. The first species was unknown; it is described in this paper and named Plasmodium coulangesi n. sp. It is characterised by--the low (6). constant number of merozoites in mature schizonts,--the disposition of the pigment, well apart from the parasitic mass to which it is linked by a tiny wisp of cytoplasm,--the normal host erythrocyte, the shape, size and colour of which are unaltered. The second species was provisionaly designated as Plasmodium sp.; it was previously seen in the same host by Garnham and Uilenberg in 1975 and designated by these authors as Plasmodium girardi Buck, Coudurier et Quesnel, 1952. Only gametocytes of the last species were found; they are similar to those of Plasmodium lemuris Huff and Hoogstraal, 1963.
Animals↗
New observations on the malaria parasites of rodents of the Central African Republic - Plasmodium vinckei petteri subsp. nov. and Plasmodium chabaudi Landau, 1965.
The morphology and enzyme forms of malaria parasites isolated from 50 wild caught specimens of Thamnomys rutilans from the Central African Republic have been studied and three distinct species of Plasmodium identified. One species has been confirmed as Plasmodium yoelii yoelii. Morphological features of both the remaining species correspond to those given by Landau (1965) in her original description of Plasmodium chabaudi. For one of these species the name P. chabaudi has been retained; the other species, which closely resembles subspecies of Plasmodium vinckei from other regions of Africa, has been designated Plasmodium vinckei petteri subsp. nov. P. chabaudi and P.v. petteri are distinguished from each other both in their morphology in the blood and sporogonic stages, and in their enzyme forms.
Animals↗
[An imported case of mixed malaria caused by Plasmodium falciparum and Plasmodium ovale.].
Malaria caused by Plasmodium species is an important parasitic infection in Turkey as in the rest of the world. Malaria cases originating in our country are caused by P. vivax; those caused by other Plasmodium spp. are imported cases. In this article, after work-related travel to Cameroon, a patient who acquired specific clinical signs and symptoms of malaria has been evaluated. The major clinical findings of the patient were fever, chills and shaking. After examination of thin and thick blood smears prepared from the peripheral blood of the patient, a 20% rate of Plasmodium parasitemia was obtained and the case was considered to be a mixed P. falciparum and P. ovale infection. In addition, P. falciparum infection was confirmed using the Optimal Malaria Rapid Test and the presence of another Plasmodium species besides P. falciparum was confirmed. Primaquine was added to quinine and doxycycline therapy for P. ovale hypnozoites. No Plasmodium was found in control blood smears after clinical improvement. In this case, it has been emphasized that in differential diagnosis of fever seen after travel to malaria endemic areas, malaria must be considered and prophylaxis must be carried out before travel.
English Abstract↗
Inhibition of the growth of Plasmodium falciparum and Plasmodium berghei by the DNA polymerase inhibitor HPMPA.
The acyclic adenosine analogue (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine [HPMPA] belongs to a class of nucleoside analogues originally described as having potent activity against a broad spectrum of DNA viruses. We examined the effects of this class of drugs on the growth of cultured Plasmodium falciparum. Strong inhibition was observed by HPMPA (ID50 = 47 nM) at concentrations more than 1000-fold less than the cytotoxic dose for human cells. 3-deaza-HPMPA was even more strongly inhibitory (ID50 = 8 nM), whereas several other acyclic nucleosides were not effective. In mice infected with Plasmodium berghei, increase of parasitaemia can be blocked for 4-6 days by a single injection of HPMPA. Repeated drug administration blocks parasite growth for prolonged periods at doses that are clinically feasible. We also determined the inhibition of several purified Plasmodium DNA polymerases by diphosphorylated HPMPA (HPMPApp). DNA polymerase alpha-like enzymes of P. falciparum and P. berghei are inhibited with an IC50 = 40 microM and a gamma-like DNA polymerase from P. falciparum is even 40-fold more sensitive to the drug. The inhibition by HPMPApp is competitive with dATP, strongly suggesting that Plasmodium DNA polymerases are targets for this class of nucleotide analogue.
Adenine↗
The use of transgenic Plasmodium berghei expressing the Plasmodium vivax antigen P25 to determine the transmission-blocking activity of sera from malaria vaccine trials.
P25 is a major surface protein of Plasmodium ookinetes. Antibodies against P25 prevent the formation of oocysts in the mosquito and thereby block transmission of the parasite through an endemic population. Plasmodium vivax transmission-blocking vaccines based on Pv25 have undergone human trials and inhibit transmission significantly. The current assay to determine transmission-blocking activity (TBA) of these sera, the 'standard membrane feeding assay', is complex and can be performed by few groups worldwide that require both mosquito breeding facilities and access to volunteers naturally infected with P.vivax--a costly, and uncontrolled source of parasites. Here we report the development of novel assays to determine TBA using two clones (Pv25DR and Pv25DR3) of transgenic rodent parasites (Plasmodium berghei) expressing Pv25. We show that oocyst development of the transgenic parasites is inhibited by monoclonal antibody against Pv25 with the same kinetics exhibited by wild type parasites when exposed to mouse monoclonal antibodies targeted to a paralogous protein P28. Human transmission-blocking sera from a clinical vaccine trial of Pv25 inhibited oocyst development of Pv25DR and Pv25DR3, whereas non-blocking sera did not. We further show transmission-blocking activity can be determined in a simple assays of ookinete development in vitro, assays that obviate the need for mosquito colonies. These results demonstrate that transgenic rodent malarias expressing proteins from human Plasmodium species can be cheap, safe, and simple tools for testing TBA from sera. To this end the cloned lines have been deposited with, and are freely available from, MR4.
Animals↗
Crystal structure of Plasmodium berghei lactate dehydrogenase indicates the unique structural differences of these enzymes are shared across the Plasmodium genus.
As Plasmodium rely extensively on homolactic fermentation for energy production, Plasmodium falciparum lactate dehydrogenase (PfLDH)--the key enzyme in this process--has previously been suggested as a novel target for antimalarials. This enzyme has distinctive kinetic and structural properties that distinguish it from its human homologues. In this study, we now describe the expression, kinetic characterisation and crystal structure determination of the LDH from Plasmodium berghei. This enzyme is seen to have a similar kinetic profile to its P. falciparum counterpart, exhibiting the characteristic lack of substrate inhibition that distinguishes plasmodial from human LDHs. The crystal structure of P. berghei lactate dehydrogenase (PbLDH) shows a very similar active site arrangement to the P. falciparum enzyme. In particular, an insertion of five amino acid residues in the active site loop creates an enlarged volume in the substrate binding site, and characteristic changes in the residues lining the NADH cofactor binding pocket result in displacement of the cofactor relative to its observed position in mammalian and all other LDH structures. These results imply the special features previously described for PfLDH may be shared across the Plasmodium genus, supporting the universal application of therapeutics targeting this enzyme.
Amino Acid Sequence↗