4,456 research outputs found
Malaria transmission after artemether-lumefantrine and dihydroartemisinin-piperaquine: a randomized trial.
No full textBACKGROUND: Artemisinin-based combination therapy (ACT) reduces the potential for malaria transmission, compared with non-ACTs. It is unclear whether this effect differs between ACTs. METHODS: A total of 298 children (age, 6 months to 10 years) with uncomplicated falciparum malaria were randomized to artemether-lumefantrine (AL; n = 153) or dihydroartemisinin-piperaquine (DP; n = 145) in Mbita, a community in western Kenya. Gametocyte carriage was determined by molecular methods on days 0, 1, 2, 3, 7, 14, 28, and 42 after treatment initiation. The gametocyte infectiousness to mosquitoes was determined by mosquito-feeding assays on day 7 after beginning therapy. RESULTS: The cumulative risk of recurrent parasitemia on day 42 after initiation of treatment, unadjusted by polymerase chain reaction findings, was 20.7% (95% confidence interval [CI], 14.4-28.2) for AL, compared with 3.7% (95% CI, 1.2-8.5) for DP (P < .001). The mean duration of gametocyte carriage was 5.5 days (95% CI, 3.6-8.5) for AL and 15.3 days (95% CI, 9.7-24.2) for DP (P = .001). The proportion of mosquitoes that became infected after feeding on blood from AL-treated children was 1.88% (43 of 2293), compared with 3.50% (83 of 2371) for those that fed on blood from DP-treated children (P = .06); the oocyst burden among mosquitoes was lower among those that fed on blood from AL-treated children (P = .005) CONCLUSIONS: While DP was associated with a longer prophylactic time after treatment, gametocyte carriage and malaria transmission to mosquitoes was lower after AL treatment. CLINICAL TRIALS REGISTRATION: NCT00868465
The Plasmodium falciparum, Nima-related kinase Pfnek-4: a marker for asexual parasites committed to sexual differentiation
No full text<b>Background</b>
Malaria parasites undergo, in the vertebrate host, a developmental switch from asexual replication to sexual differentiation leading to the formation of gametocytes, the only form able to survive in the mosquito vector. Regulation of the onset of the sexual phase remains largely unknown and represents an important gap in the understanding of the parasite's complex biology.
<b>Methods:</b>
The expression and function of the Nima-related kinase Pfnek-4 during the early sexual development of the human malaria parasite Plasmodium falciparum were investigated, using three types of transgenic Plasmodium falciparum 3D7 lines: (i) episomally expressing a Pfnek-4-GFP fusion protein under the control of its cognate pfnek-4 promoter; (ii) episomally expressing negative or positive selectable markers, yeast cytosine deaminase-uridyl phosphoribosyl transferase, or human dihydrofolate reductase, under the control of the pfnek-4 promoter; and (iii) lacking a functional pfnek-4 gene. Parasite transfectants were analysed by fluorescence microscopy and flow cytometry. In vitro growth rate and gametocyte formation were determined by Giemsa-stained blood smears.
<b>Results:</b>
The Pfnek-4-GFP protein was found to be expressed in stage II to V gametocytes and, unexpectedly, in a subset of asexual-stage parasites undergoing schizogony. Culture conditions stimulating gametocyte formation resulted in significant increase of this schizont subpopulation. Moreover, sorted asexual parasites expressing the Pfnek-4-GFP protein displayed elevated gametocyte formation when returned to in vitro culture in presence of fresh red blood cells, when compared to GFP- parasites from the same initial population. Negative selection of asexual parasites expressing pfnek-4 showed a marginal reduction in growth rate, whereas positive selection caused a marked reduction in parasitaemia, but was not sufficient to completely abolish proliferation. Pfnek-4- clones are not affected in their asexual growth and produced normal numbers of stage V gametocytes.
<b>Conclusions:</b>
The results indicate that Pfnek-4 is not strictly gametocyte-specific, and is expressed in a small subset of asexual parasites displaying high rate conversion to sexual development. Pfnek-4 is not required for erythrocytic schizogony and gametocytogenesis. This is the first study to report the use of a molecular marker for the sorting of sexually-committed schizont stage P. falciparum parasites, which opens the way to molecular characterization of this pre-differentiated subpopulation
Molecular monitoring of Plasmodium falciparum resistance to artemisinin in Tanzania.
No full textArtemisinin-based combination therapies (ACTs) are recommended for use against uncomplicated malaria in areas of multi-drug resistant malaria, such as sub-Saharan Africa. However, their long-term usefulness in these high transmission areas remains unclear. It has been suggested that documentation of the S769N PfATPase6 mutations may indicate an emergence of artemisinin resistance of Plasmodium falciparum in the field. The present study assessed PfATPase6 mutations (S769N and A623E) in 615 asymptomatic P. falciparum infections in Tanzania but no mutant genotype was detected. This observation suggests that resistance to artemisinin has not yet been selected in Tanzania, supporting the Ministry of Health's decision to adopt artemether+lumefantrine as first-line malaria treatment. The findings recommend further studies to assess PfATPase6 mutations in sentinel sites and verify their usefulness in monitoring emergency of ACT resistance
Isrogrogidda Falka Af-soomaaliga: Aragti ku aadan Midaynta Qoraalkiisa
No full textQoraagu wuxuu diraasad ku sameeyey sidii loo midayn lahaa af Soomaaliga qoraaal ahaan loo adeegsada. Gaar ahaan wuxuu diiradda saarayaa sidii loo midayn lahaa qaababka isrogrogga falalka oo haatan loo adeegsado siyaabo aan midaysanayn.In questo articolo, l'autore analizza e avanza una proposta relativamente alla standardizzazione del somalo scritto, in particolar modo delle forme di coniugazione dei verbi somali che attualmente non sono scritte in modo omogenea.In this article, the author analyzes and provides a proposal about the standardization of written Somali, in particular relating to verb conjugation forms whose orthography still differs today.Cabdirashid M. Ismaaciil, Cabdalla C. Mansuur, Saynab A. Sharci (eds.
Coastal Research and its Economic Justification
No full textProper and thorough planning of coastal engineering projects is discussed and the economie justification of research work indicated. Examples are given concerning navigational problems, coastal protection problems, and harbor sediment problems.KWP-collectio
Expression of Plasmodium falciparum genes involved in erythrocyte invasion varies among isolates cultured directly from patients.
No full textPlasmodium falciparum merozoites invade erythrocytes using a range of alternative ligands that includes erythrocyte binding antigenic proteins (EBAs) and reticulocyte binding protein homologues (Rh). Variation in the expression of some of these genes among culture-adapted parasite lines correlates with the use of different erythrocyte receptors. Here, expression profiles of four Rh genes and eba175 are analysed in a sample of 42 isolates cultured from malaria patients in Kenya. The profiles cluster into distinct groups, largely because of very strong negative correlations between the levels of expression of particular gene pairs (Rh1 versus Rh2b, eba175 versus Rh2b, and eba175 versus Rh4), previously associated with alternative invasion pathways in culture-adapted parasite lines. High levels of eba175 are seen in isolates in expression profile group I, and may be associated with sialic acid-dependent invasion. Groups II and III are, respectively, characterized by high levels of Rh2b and Rh4, and are more likely to be associated with sialic acid-independent invasion
Midaynta iyo Horumarinta Af-soomaaliga
No full textQoraagu wuxuu maqaalkan ku falanqaynayaa arrimo ku saabsan midaynta af Soomaaliga qoran, oo dadka qaarkood ay ku doodaan in ay dhibaato ka taagantahay, iyagoo u aanaynaya kala duwanaanta lahjadaha Soomaaliyeed iyo farta af Soomaaliga oo aan xasillayn. Qoraha oo soo bandhigayaa in arrimahaasu aanu sax ahayn, wuxuuna muujinayaa caqabadaha dhabta ah ee hortaagan houmarinta af Soomaaliga: afku wuxuu la'yahay dawlad si rasmi ah u adeegsato, weerar ba'anna waxaa ku haya af Ingiriisiga, xagga ereyadana nabaadguur xooggan ayaa ku dhacaya, gaar ahaan ereyada la xiriira dhaqanka Soomaaliyeed.L'autore, in questo articolo, analizzando la questione della lingua somala scritta, cerca di illustrare che la situazione del somalo standard non è cosi problematica come a detta di alcuni somali, specialmente, nell'ortografia e nella differenza tra i dialetti, ma il problema somalo è bensì riscontrabile in altri fattori: la mancanza di un stato che continui ad adottare il somalo come lingua ufficiale, l'estinzione di tantissimi vocaboli in disuso, nonché la forte influenza dalla lingua inglese.The author in this article, in analysing the written somali language, wants to show the somali standard situation is not so bad, like some Somalis say, especially in orthography and in vernaculars difference. In spite of, the somali language problem is recognisable in some others factors: lack of state that usually chooses somali language as official language, extinction of many terms in disuse and also the strong influence of English.Cabdirashid M. Ismaaciil, Cabdalla C. Mansuur, Saynab A. Sharci (eds.
A well-conserved Plasmodium falciparum var gene shows an unusual stage-specific transcript pattern
No full textThe var multicopy gene family encodes Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) variant antigens, which, through their ability to adhere to a variety of host receptors, are thought to be important virulence factors. The predominant expression of a single cytoadherent PfEMP1 type on an infected red blood cell, and the switching between different PfEMP1 types to evade host protective antibody responses, are processes thought to be controlled at the transcriptional level. Contradictory data have been published on the timing of var gene transcription. Reverse transcription-polymerase chain reaction (RT-PCR) data suggested that transcription of the predominant var gene occurs in the later (pigmented trophozoite) stages, whereas Northern blot data indicated such transcripts only in early (ring) stages. We investigated this discrepancy by Northern blot, with probes covering a diverse var gene repertoire. We confirm that almost all var transcript types were detected only in ring stages. However, one type, the well-conserved varCSA transcript, was present constitutively in different laboratory parasites and does not appear to undergo antigenic variation. Although varCSA has been shown to encode a chondroitin sulphate A (CSA)-binding PfEMP1, we find that the presence of full-length varCSA transcripts does not correlate with the CSA-binding phenotype
Om inloppet ifrån Östersjön : till SöderTelje eller Egelsta wiken
No full textAuthor: Nathanael Gerhard af Schultén.Dated: "Carlberg den 12 Januari 1806."Digital reproduction, The National Library of Finland, Centre for Preservation and Digitisation, MikkeliA description of the Baltic Sea.TravelEuropeanaSchultén, Nathanael Gerhard af (1750-1825
Artemether resistance in vitro is linked to mutations in PfATP6 that also interact with mutations in PfMDR1 in travellers returning with Plasmodium falciparum infections.
No full textBACKGROUND: Monitoring resistance phenotypes for Plasmodium falciparum, using in vitro growth assays, and relating findings to parasite genotype has proved particularly challenging for the study of resistance to artemisinins.
METHODS: Plasmodium falciparum isolates cultured from 28 returning travellers diagnosed with malaria were assessed for sensitivity to artemisinin, artemether, dihydroartemisinin and artesunate and findings related to mutations in pfatp6 and pfmdr1.
RESULTS: Resistance to artemether in vitro was significantly associated with a pfatp6 haplotype encoding two amino acid substitutions (pfatp6 A623E and S769N; (mean IC50 (95% CI) values of 8.2 (5.7 - 10.7) for A623/S769 versus 623E/769 N 13.5 (9.8 - 17.3) nM with a mean increase of 65%; p = 0.012). Increased copy number of pfmdr1 was not itself associated with increased IC50 values for artemether, but when interactions between the pfatp6 haplotype and increased copy number of pfmdr1 were examined together, a highly significant association was noted with IC50 values for artemether (mean IC50 (95% CI) values of 8.7 (5.9 - 11.6) versus 16.3 (10.7 - 21.8) nM with a mean increase of 87%; p = 0.0068). Previously described SNPs in pfmdr1 are also associated with differences in sensitivity to some artemisinins.
CONCLUSIONS: These findings were further explored in molecular modelling experiments that suggest mutations in pfatp6 are unlikely to affect differential binding of artemisinins at their proposed site, whereas there may be differences in such binding associated with mutations in pfmdr1. Implications for a hypothesis that artemisinin resistance may be exacerbated by interactions between PfATP6 and PfMDR1 and for epidemiological studies to monitor emerging resistance are discussed
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