Search

Your search keyword '"Mackinnon, Margaret J."' showing total 147 results
Start Over Author "Mackinnon, Margaret J."
147 results on '"Mackinnon, Margaret J."'

8. Evolutionary genetics of malaria parasites

Author

Mackinnon, Margaret J.

Subjects
591.35
Abstract

Two empirical studies on parasite virulence using the laboratory model of the rodent malaria parasite, Plasmodium chabaudi, in inbred mice, were conducted. In the first, the average virulence and transmissibility in eight parasite clones obtained from the wild were measured over four replicate experiments. Large amounts of genetic (between-clone) variation in virulence and transmissibility were observed. Virulence was strongly correlated, both phenotypically and genetically, to population growth rate (parasitaemia) and less strongly correlated to transmissibility. These results provide strong support for the basic tenet of most evolutionary models of parasite virulence, namely, that virulence is a by-product of the parasite's need to replicate fast in order to be transmitted. In the second study, between-host selection for high and low virulence was performed within two parasite clones. Over eleven generations, all the selection lines increased in virulence and transmissibility. Thus, despite artificial between-host selection, parasitic variation within clones coupled with inadvertent within-host selection, allowed the parasite to adapt to a novel host. Together, these studies show that virulence is strongly determined by parasite genetics. A large data set on disease severity from a 3-year longitudinal field study in Sri Lanka was analysed for the effects of host genetic variability, age, immune experience, parasite species (P. falciparum vs. P. vivax), bednet use, sex and other host or environmental factors. The results highlighted the importance of short-term acquired immunity in causing large between-host variation in virulence. This is consistent with the view that parasite variability is responsible for inefficient clinical immunity to malarial disease, although this could not be examined directly and alternative explanations are possible. Two theoretical models incorporating parasite population structure into population genetics were used to predict the probability and rate of evolution of multi-locus drug resistance. All of these studies suggest that parasite genetic variation plays a key role in the evolution of the malaria host-parasite association.

Published
1998

18. The effects of selection on linkage analysis for quantitative traits

Author

Mackinnon, Margaret J. and Georges, Michel A.J.

Subjects
Linkage (Genetics) -- Research, Quantitative genetics -- Research, Biological sciences
Abstract

A study was conducted to evaluate effects of within-sample selection on linkage analyses between genetic markers and quantitative traits. Results show that truncation for the trait of interest decreases variation between marker genotype means. The process reduces the power to identify linked quantitative trait loci (QTL). The reduction size is conditioned by proportion selected, magnitude of QTL effect, recombination rate between marker locus and QTL and QTL allele frequency.

Published
1992

20. Artemisinin resistance in Plasmodium falciparum is associated with an altered temporal pattern of transcription

Author

Newton Paul N, Socheat Duong, Russell Bruce, Liong Kek-Yee, Chotivanich Kesinee, Mayxay Mayfong, Yi Poravuth, Ramadoss Ramya, Sim Joan, Mackinnon Margaret J, Imwong Mallika, Mok Sachel, Day Nicholas PJ, White Nicholas J, Preiser Peter R, Nosten François, Dondorp Arjen M, and Bozdech Zbynek

Subjects
Plasmodium falciparum, in vivo artemisinin-resistance, field isolates, comparative genomics, comparative transcriptomics, Biotechnology, TP248.13-248.65, Genetics, QH426-470
Abstract

Abstract Background Artemisinin resistance in Plasmodium falciparum malaria has emerged in Western Cambodia. This is a major threat to global plans to control and eliminate malaria as the artemisinins are a key component of antimalarial treatment throughout the world. To identify key features associated with the delayed parasite clearance phenotype, we employed DNA microarrays to profile the physiological gene expression pattern of the resistant isolates. Results In the ring and trophozoite stages, we observed reduced expression of many basic metabolic and cellular pathways which suggests a slower growth and maturation of these parasites during the first half of the asexual intraerythrocytic developmental cycle (IDC). In the schizont stage, there is an increased expression of essentially all functionalities associated with protein metabolism which indicates the prolonged and thus increased capacity of protein synthesis during the second half of the resistant parasite IDC. This modulation of the P. falciparum intraerythrocytic transcriptome may result from differential expression of regulatory proteins such as transcription factors or chromatin remodeling associated proteins. In addition, there is a unique and uniform copy number variation pattern in the Cambodian parasites which may represent an underlying genetic background that contributes to the resistance phenotype. Conclusions The decreased metabolic activities in the ring stages are consistent with previous suggestions of higher resilience of the early developmental stages to artemisinin. Moreover, the increased capacity of protein synthesis and protein turnover in the schizont stage may contribute to artemisinin resistance by counteracting the protein damage caused by the oxidative stress and/or protein alkylation effect of this drug. This study reports the first global transcriptional survey of artemisinin resistant parasites and provides insight to the complexities of the molecular basis of pathogens with drug resistance phenotypes in vivo.

Published
2011
Full Text
View/download PDF

21. Establishing the extent of malaria transmission and challenges facing pre-elimination in the Republic of Djibouti

Author

Drakeley Christopher J, Cook Jackie, Nyonda Mary, Ahmed Ifrah A, Kabaria Caroline W, Guessod Hawa H, Osman Mouna A, Mugyenyi Cleopatra K, Mohamed Maoulid B, Noor Abdisalan M, Mackinnon Margaret J, and Snow Robert W

Subjects
Infectious and parasitic diseases, RC109-216
Abstract

Abstract Background Countries aiming for malaria elimination require a detailed understanding of the current intensity of malaria transmission within their national borders. National household sample surveys are now being used to define infection prevalence but these are less efficient in areas of exceptionally low endemicity. Here we present the results of a national malaria indicator survey in the Republic of Djibouti, the first in sub-Saharan Africa to combine parasitological and serological markers of malaria, to evaluate the extent of transmission in the country and explore the potential for elimination. Methods A national cross-sectional household survey was undertaken from December 2008 to January 2009. A finger prick blood sample was taken from randomly selected participants of all ages to examine for parasitaemia using rapid diagnostic tests (RDTs) and confirmed using Polymerase Chain Reaction (PCR). Blood spots were also collected on filter paper and subsequently used to evaluate the presence of serological markers (combined AMA-1 and MSP-119) of Plasmodium falciparum exposure. Multivariate regression analysis was used to determine the risk factors for P. falciparum infection and/or exposure. The Getis-Ord G-statistic was used to assess spatial heterogeneity of combined infections and serological markers. Results A total of 7151 individuals were tested using RDTs of which only 42 (0.5%) were positive for P. falciparum infections and confirmed by PCR. Filter paper blood spots were collected for 5605 individuals. Of these 4769 showed concordant optical density results and were retained in subsequent analysis. Overall P. falciparum sero-prevalence was 9.9% (517/4769) for all ages; 6.9% (46/649) in children under the age of five years; and 14.2% (76/510) in the oldest age group (≥ 50 years). The combined infection and/or antibody prevalence was 10.5% (550/4769) and varied from 8.1% to 14.1% but overall regional differences were not statistically significant (χ2 = 33.98, p = 0.3144). Increasing age (p < 0.001) and decreasing household wealth status (p < 0.001) were significantly associated with increasing combined P. falciparum infection and/or antibody prevalence. Significant P. falciparum hot spots were observed in Dikhil region. Conclusion Malaria transmission in the Republic of Djibouti is very low across all regions with evidence of micro-epidemiological heterogeneity and limited recent transmission. It would seem that the Republic of Djibouti has a biologically feasible set of pre-conditions for elimination, however, the operational feasibility and the potential risks to elimination posed by P. vivax and human population movement across the sub-region remain to be properly established.

Published
2011
Full Text
View/download PDF

22. Adaptation of Plasmodium falciparum to its transmission environment

Author

Rono, Martin K., primary, Nyonda, Mary A., additional, Simam, Joan J., additional, Ngoi, Joyce M., additional, Mok, Sachel, additional, Kortok, Moses M., additional, Abdullah, Abdullah S., additional, Elfaki, Mohammed M., additional, Waitumbi, John N., additional, El-Hassan, Ibrahim M., additional, Marsh, Kevin, additional, Bozdech, Zbynek, additional, and Mackinnon, Margaret J., additional

Published
2017
Full Text
View/download PDF

23. New antigens for multi-component blood-stage vaccines against Plasmodium falciparum malaria

Author

Osier, Faith H, Mackinnon, Margaret J, Crosnier, Cécile, Fegan, Gregory, Kamuyu, Gathoni, Wanaguru, Madushi, Ogada, Edna, McDade, Brian, Rayner, Julian C, Wright, Gavin J, and Marsh, Kevin

Subjects
Time Factors, Merozoites, Plasmodium falciparum, Age Factors, Infant, Newborn, Protozoan Proteins, Antibodies, Protozoan, Infant, Antigens, Protozoan, Kenya, Article, Peptide Fragments, Seroepidemiologic Studies, Child, Preschool, parasitic diseases, Malaria Vaccines, Humans, Prospective Studies, Malaria, Falciparum, Child, Biomarkers
Abstract

An effective blood stage vaccine against Plasmodium falciparum remains a research priority but the number of antigens that have been translated to candidates for testing in clinical trials remains limited. Investigations of the large number of potential targets found in the parasite proteome have been constrained by an inability to produce natively folded recombinant antigens for immunological studies. We overcame these constraints by generating a large library of demonstrably biochemically active merozoite surface and secreted full-length ectodomain proteins. We then systematically examined the antibody reactivity against these proteins in a cohort of Kenyan children (n=286) who were sampled at the start of a malaria transmission season and prospectively monitored for clinical episodes of malaria over the ensuing six months. We found that antibodies to previously untested or little-studied proteins had superior or equivalent potential protective efficacy to the handful of current leading malaria vaccine candidates. Moreover, cumulative responses to combinations comprising five of the ten top ranked antigens, including PF3D7_1136200, MSP2, RhopH3, P41, MSP11, MSP3, PF3D7_0606800, AMA1, Pf113 and MSRP1 were associated with 100% protection against clinical episodes of malaria. These data suggest that not only are there many more potential vaccine candidates for the vaccine development pipeline, but also that highly effective vaccination may be achieved through combining a selection of these antigens as observed in nature.

Published
2014

25. New antigens for a multicomponent blood-stage malaria vaccine

Author

Osier, Faith H., primary, Mackinnon, Margaret J., additional, Crosnier, Cécile, additional, Fegan, Gregory, additional, Kamuyu, Gathoni, additional, Wanaguru, Madushi, additional, Ogada, Edna, additional, McDade, Brian, additional, Rayner, Julian C., additional, Wright, Gavin J., additional, and Marsh, Kevin, additional

Published
2014
Full Text
View/download PDF

29. Artemisinin resistance in Plasmodium falciparum is associated with an altered temporal pattern of transcription

Author

Mok, Sachel, primary, Imwong, Mallika, additional, Mackinnon, Margaret J, additional, Sim, Joan, additional, Ramadoss, Ramya, additional, Yi, Poravuth, additional, Mayxay, Mayfong, additional, Chotivanich, Kesinee, additional, Liong, Kek-Yee, additional, Russell, Bruce, additional, Socheat, Duong, additional, Newton, Paul N, additional, Day, Nicholas PJ, additional, White, Nicholas J, additional, Preiser, Peter R, additional, Nosten, François, additional, Dondorp, Arjen M, additional, and Bozdech, Zbynek, additional

Published
2011
Full Text
View/download PDF

30. Establishing the extent of malaria transmission and challenges facing pre-elimination in the Republic of Djibouti

Author

Noor, Abdisalan M, primary, Mohamed, Maoulid B, additional, Mugyenyi, Cleopatra K, additional, Osman, Mouna A, additional, Guessod, Hawa H, additional, Kabaria, Caroline W, additional, Ahmed, Ifrah A, additional, Nyonda, Mary, additional, Cook, Jackie, additional, Drakeley, Christopher J, additional, Mackinnon, Margaret J, additional, and Snow, Robert W, additional

Published
2011
Full Text
View/download PDF

34. Breadth and Magnitude of Antibody Responses to MultiplePlasmodium falciparumMerozoite Antigens Are Associated with Protection from Clinical Malaria

Author

Osier, Faith H. A., primary, Fegan, Gregory, additional, Polley, Spencer D., additional, Murungi, Linda, additional, Verra, Federica, additional, Tetteh, Kevin K. A., additional, Lowe, Brett, additional, Mwangi, Tabitha, additional, Bull, Peter C., additional, Thomas, Alan W., additional, Cavanagh, David R., additional, McBride, Jana S., additional, Lanar, David E., additional, Mackinnon, Margaret J., additional, Conway, David J., additional, and Marsh, Kevin, additional

Published
2008
Full Text
View/download PDF

36. LOW MULTIPLICATION RATES OF AFRICAN PLASMODIUM FALCIPARUM ISOLATES AND LACK OF ASSOCIATION OF MULTIPLICATION RATE AND RED BLOOD CELL SELECTIVITY WITH MALARIA VIRULENCE

Author

DEANS, ANNE-MARIE, primary, PLOWE, CHRISTOPHER V., additional, MACKINNON, MARGARET J., additional, DOUMBO, OGOBARA K., additional, RAZA, AHMED, additional, KONÉ, ABDOULAYE, additional, LYKE, KIRSTEN E., additional, MARSH, KEVIN, additional, KAI, OSCAR, additional, ROWE, J. ALEXANDRA, additional, and THERA, MAHAMADOU A., additional

Published
2006
Full Text
View/download PDF

40. GENETIC COMPLEXITY OF PLASMODIUM FALCIPARUM IN TWO ETHNIC GROUPS OF BURKINA FASO WITH MARKED DIFFERENCES IN SUSCEPTIBILITY TO MALARIA

Author

PAGANOTTI, GIACOMO M., primary, OUÉDRAOGO, ANDRÉ L., additional, COLUZZI, MARIO, additional, SIRIMA, BIENVENU S., additional, MODIANO, DAVID, additional, WALLIKER, DAVID, additional, KONATÉ, AMADOU, additional, VERRA, FEDERICA, additional, MACKINNON, MARGARET J., additional, DIARRA, AMIDOU, additional, and BABIKER, HAMZA A., additional

Published
2004
Full Text
View/download PDF

44. Microbial evolution (Communication arising): Antitoxin vaccines and pathogen virulence

Author

Gandon, Sylvain, Mackinnon, Margaret J., Nee, Sean, and Read, Andrew F.

Subjects
Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Author(s): Sylvain Gandon (corresponding author); Margaret J. Mackinnon; Sean Nee; Andrew F. Read Gandon et al . reply Soubeyrand and Plotkin question our contention that antitoxin vaccines may select for [...]

Published
2002
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results