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Query: UMLS:C0024530 (malaria)
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Since the 1970's, the diversity of Plasmodium parasites in African great apes has been neglected. Surprisingly, P. reichenowi, a chimpanzee parasite, is the only such parasite to have been molecularly characterized. This parasite is closely phylogenetically related to P. falciparum, the principal cause of the greatest malaria burden in humans. Studies of malaria parasites from anthropoid primates may provide relevant phylogenetic information, improving our understanding of the origin and evolutionary history of human malaria species. In this study, we screened 130 DNA samples from chimpanzees (Pan troglodytes) and gorillas (Gorilla gorilla) from Cameroon for Plasmodium infection, using cytochrome b molecular tools. Two chimpanzees from the subspecies Pan t. troglodytes presented single infections with Plasmodium strains molecularly related to the human malaria parasite P. ovale. These chimpanzee parasites and 13 human strains of P. ovale originated from a various sites in Africa and Asia were characterized using cytochrome b and cytochrome c oxidase 1 mitochondrial partial genes and nuclear ldh partial gene. Consistent with previous findings, two genetically distinct types of P. ovale, classical and variant, were observed in the human population from a variety of geographical locations. One chimpanzee Plasmodium strain was genetically identical, on all three markers tested, to variant P. ovale type. The other chimpanzee Plasmodium strain was different from P. ovale strains isolated from humans. This study provides the first evidence of possibility of natural cross-species exchange of P. ovale between humans and chimpanzees of the subspecies Pan t. troglodytes.
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PMID:Chimpanzee malaria parasites related to Plasmodium ovale in Africa. 1943 42

Atovaquone is a substituted 2-hydroxy-naphthoquinone used therapeutically against Plasmodium falciparum (malaria) and Pneumocystis pathogens. It acts by inhibiting the cytochrome bc(1) complex via interactions with the Rieske iron-sulfur protein and cytochrome b in the ubiquinol oxidation pocket. As the targeted pathogens have developed resistance to this drug there is an urgent need for new alternatives. To better understand the determinants of inhibitor binding in the ubiquinol oxidation pocket of the bc(1) complex we synthesized a series of hydroxy-naphthoquinones bearing a methyl group on the benzene ring that is predicted to interact with the nuclear encoded Rieske iron-sulfur protein. We have also attempted to overcome the metabolic instability of a potent cytochrome bc(1) complex inhibitor, a 2-hydroxy-naphthoquinone with a branched side chain, by fluorinating the terminal methyl group. We have tested these new 2-hydroxy-naphthoquinones against yeast and bovine cytochrome bc(1) complexes to model the interaction with pathogen and human enzymes and determine parameters that affect efficacy of binding of these inhibitors. We identified a hydroxy-naphthoquinone with a trifluoromethyl function that has potential for development as an anti-fungal and anti-parasitic therapeutic.
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PMID:Probing binding determinants in center P of the cytochrome bc(1) complex using novel hydroxy-naphthoquinones. 1966 Apr 31

Assessing parasite specificity to vector is crucial to understanding the emergence of vector-borne diseases and the evolution of parasite diversity. Avian malaria parasites have a cosmopolitan distribution and broad avian host range, which together predict they are vector generalists, but little is known about parasite-vector associations in the wild. We tested this prediction by asking if 5 different mosquito species, known to feed on birds and abundant in the northeastern United States, were naturally infected in the field with identical avian Plasmodium spp. lineages. Mosquitoes were not pooled but rather analyzed individually, and, possibly as a result, lineage diversity was higher than reported in previous avian malaria vector studies. Plasmodium spp. lineages were rare in Aedes canadensis and absent in Aedes aurifer and Culiseta melanura. We sequenced a standard Plasmodium cytochrome b marker from Culex pipiens pipiens, Culex restuans, and Ae. canadensis. Most Plasmodium clades were shared by Cx. pipiens and Cx. restuans. In addition, 4 individual lineages were shared by both mosquito species, including the most common lineage. One Plasmodium clade, however, was only found in Cx. restuans. We therefore found limited support for our prediction that avian Plasmodium spp. vector breadth accompanies host breadth. The association of both Culex species with most Plasmodium clades, and the presence of a single parasite lineage in 3 mosquito species representing 2 genera, suggests that avian Plasmodium species are not tightly coevolved with vector species.
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PMID:Avian malaria parasites share congeneric mosquito vectors. 1969 68

Land use changes including deforestation, road construction and agricultural encroachments have been linked to the increased prevalence of several infectious diseases. In order to better understand how deforestation affects the prevalence of vector-borne infectious diseases in wildlife, nine paired sites were sampled (disturbed vs. undisturbed habitats) in Southern Cameroon. We studied the diversity, prevalence and distribution of avian malaria parasites (Plasmodium spp.) and other related haemosporidians (species of Haemoproteus and Leucocytozoon) from these sites in two widespread species of African rainforest birds, the yellow-whiskered greenbul (Andropadus latirostris, Pycnonotidae) and the olive sunbird (Cyanomitra olivacea, Nectariniidae). Twenty-six mitochondrial cytochrome b lineages were identified: 20 Plasmodium lineages and 6 Haemoproteus lineages. These lineages showed no geographic specificity, nor significant differences in lineage diversity between habitat types. However, we found that the prevalence of Leucocytozoon and Haemoproteus infections were significantly higher in undisturbed than in deforested habitats (Leucocytozoon spp. 50.3% vs. 35.8%, Haemoproteus spp. 16.3% vs. 10.8%). We also found higher prevalence for all haemosporidian parasites in C. olivacea than in A. latirostris species (70.2% vs. 58.2%). Interestingly, we found one morphospecies of Plasmodium in C. olivacea, as represented by a clade of related lineages, showed increased prevalence at disturbed sites, while another showed a decrease, testifying to different patterns of transmission, even among closely related lineages of avian malaria, in relation to deforestation. Our work demonstrates that anthropogenic habitat change can affect host-parasite systems and result in opposing trends in prevalence of haemosporidian parasites in wild bird populations.
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PMID:Prevalence and diversity patterns of avian blood parasites in degraded African rainforest habitats. 1975 13

Anopheles funestus, one of the main African malaria vectors, caused a major malaria outbreak in South Africa during 1999/2000, even though South Africa had an effective vector control program in place. The outbreak was due to pyrethroid resistant An. funestus invading KwaZulu/Natal. Increased activity of cytochrome P450 (monooxygenase) was responsible for the pyrethroid resistance in this species. A monooxygenase gene, CYP6P9, was highly overexpressed in the pyrethroid-resistant strain compared with a susceptible strain. Characterization of this gene as well as the redox partners involved in the catalytic cycle of P450s was investigated. The full length of the CYP6P9 sequence was isolated, sequenced and compared between the pyrethroid-resistant and -susceptible strains. Sequence identity between the two strains was 99.3%; the sequence differences were mainly outside of the conserved regions. The functional significance is still unknown, but it is feasible that these variations are associated with differences in insecticide metabolism. A second CYP6 gene (CYP6P13) was also isolated; it shared close similarities with CYP6P9. The putative redox partners, cytochrome b(5) (cyt b(5)) and NADPH-cytochrome P450 reductase (CPR), were isolated from An. funestus (resistant strain) and showed high levels of sequence identity to other insect cyt b(5) and CPRs. Isolation of the coding sequences CYP6P9 and its cognate redox partners enables expression of functional recombinant protein for biochemical and structural analysis.
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PMID:Sequence characterization of cytochrome P450 CYP6P9 in pyrethroid resistant and susceptible Anopheles funestus (Diptera: Culicidae). 2039 40

Very slight sequence differences in the mitochondrial cytochrome b gene, even single nucleotide substitutions, have been proposed as indicative of different species of avian malaria parasites. However, few studies have examined within-species variation in that gene for Plasmodium or related genera. We examined sequences for the entire cytochrome b gene from Plasmodium mexicanum , a parasite of lizards, for sites where microsatellite markers revealed substantial genetic diversity. For sites where the parasite is geographically genetically differentiated, and may have been isolated for thousands of years, there was no sequence variation (1,153 nucleotides) for >160 infections studied. The low degree of variation found in the cytochrome b gene for two human malaria parasites world-wide, as well as the lack of variation for P. mexicanum , contrast with the substantial variation found in surveys of bird malaria parasites, even in restricted geographic regions.
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PMID:Lack of sequence variation of the mitochondrial cytochrome b gene from a malaria parasite, Plasmodium mexicanum. 2047 6

Phylogenetic analyses of the mitochondrial cytochrome b (cytb), apicoplast caseinolytic protease C (clpC), and 18S rRNA sequences of Plasmodium isolates from chimpanzees along with those of the virulent human malaria parasite P. falciparum showed that the common chimpanzee (Pan troglodytes) malaria parasites, assigned by Rich et al. (2009) to P. reichenowi, constitute a paraphyletic assemblage. The assumption that P. falciparum diverged from P. reichenowi as recently as 5000-50,000 years ago would require a rate of synonymous substitution/site/year in cytb and clpC on the order of 10(-5)-10(-6), several orders of magnitude higher than any known from eukaryotic organelle genomes, and would imply an unrealistically recent timing of the most recent common ancestor of P. falciparum mitochondrial genomes. The available data are thus most consistent with the hypothesis that P. reichenowi (in the strict sense) and P. falciparum co-speciated with their hosts about 5-7 million years ago.
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PMID:Malaria parasite sequences from chimpanzee support the co-speciation hypothesis for the origin of virulent human malaria (Plasmodium falciparum). 2054 13

The evolutionary origins of new lineages of pathogens are fundamental to understanding emerging diseases. Phylogenetic reconstruction based on DNA sequences has revealed the sister taxa of human pathogens, but the timing of host-switching events, including the human malaria pathogen Plasmodium falciparum, remains controversial. Here, we establish a rate for cytochrome b evolution in avian malaria parasites relative to its rate in birds. We found that the parasite cytochrome b gene evolves about 60% as rapidly as that of host cytochrome b, corresponding to approximately 1.2% sequence divergence per million years. This calibration puts the origin of P. falciparum at 2.5 million years ago (Ma), the initial radiation of mammalian Plasmodium at 12.8 Ma, and the contemporary global diversity of the Haemosporida across terrestrial vertebrates at 16.2 Ma.
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PMID:A molecular clock for malaria parasites. 2061 81

Although malaria parasites infecting non-human primates are important models for human malaria, little is known of the ecology of infection by these parasites in the wild. We extensively sequenced cytochrome b (cytb) of malaria parasites (Apicomplexa: Haemosporida) from free-living southeast Asian monkeys Macaca nemestrina and Macaca fascicularis. The two most commonly observed taxa were Plasmodium inui and Hepatocystis sp., but certain other sequences did not cluster closely with any previously sequenced species. Most of the major clades of parasites were found in both Macaca species, and the two most commonly occurring parasite infected the two Macaca species at approximately equal levels. However, P. inui showed evidence of genetic differentiation between the populations infecting the two Macaca species, suggesting limited movement of this parasite among hosts. Moreover, coinfection with Plasmodium and Hepatocystis species occurred significantly less frequently than expected on the basis of the rates of infection with either taxon alone, suggesting the possibility of competitive exclusion. The results revealed unexpectedly complex communities of Plasmodium and Hepatocystis taxa infecting wild southeast Asian monkeys. Parasite taxa differed with respect to both the frequency of between-host movement and their frequency of coinfection.
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PMID:Ecology of malaria parasites infecting Southeast Asian macaques: evidence from cytochrome b sequences. 2064 16

Whereas some bird species are heavily affected by blood parasites in the wild, others reportedly are not. Seabirds, in particular, are often free from blood parasites, even in the presence of potential vectors. By means of polymerase chain reaction, we amplified a DNA fragment from the cytochrome b gene to detect parasites of the genera Plasmodium, Leucocytozoon, and Haemoproteus in 14 seabird species, ranging from Antarctica to the tropical Indian Ocean. We did not detect parasites in 11 of these species, including one Antarctic, four subantarctic, two temperate, and four tropical species. On the other hand, two subantarctic species, thin-billed prions Pachyptila belcheri and dolphin gulls Larus scoresbii, were found infected. One of 28 thin-billed prions had a Plasmodium infection whose DNA sequence was identical to lineage P22 of Plasmodium relictum, and one of 20 dolphin gulls was infected with a Haemoproteus lineage which appears phylogenetically clustered with parasites species isolated from passeriform birds such as Haemoproteus lanii, Haemoproteus magnus, Haemoproteus fringillae, Haemoproteus sylvae, Haemoproteus payevskyi, and Haemoproteus belopolskyi. In addition, we found a high parasite prevalence in a single tropical species, the Christmas Island frigatebird Fregata andrewsi, where 56% of sampled adults were infected with Haemoproteus. The latter formed a monophyletic group that includes a Haemoproteus line from Eastern Asian black-tailed gulls Larus crassirostris. Our results are in agreement with those showing that (a) seabirds are poor in hemosporidians and (b) latitude could be a determining factor to predict the presence of hemosporidians in birds. However, further studies should explore the relative importance of extrinsic and intrinsic factors on parasite prevalence, in particular using phylogenetically controlled comparative analyses, systematic sampling and screening of vectors, and within-species comparisons.
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PMID:Hemosporidian blood parasites in seabirds--a comparative genetic study of species from Antarctic to tropical habitats. 2065 73


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