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Naturally acquired immunity to plasmodium falciparum malaria : antibody responses and immunological memory
No full textPlasmodium falciparum malaria is a significant public health concern particularly in Sub-Saharan Africa. Effective malaria vaccines will contribute significantly towards controlling the disease but their development is hampered by the incomplete understanding of immunity to malaria. Whereas naturally acquired immunity is known to have an important antibody mediated component, the targets and functional correlates as well longevity of these responses are largely unknown and merit further understanding. The studies presented in this thesis, investigate several aspects of naturally acquired immunity to some of the major merozoite vaccine candidate antigens.In longitudinally monitored children in Tanzania, antibody responses against seven merozoite surface antigens were investigated in relation to the genetic diversity of P. falciparum infections, as determined by genotyping of one of the merozoite surface protein genes. The breadth of anti-merozoite antibody responses was positively correlated with the number of concurrent P. falciparum clones in asymptomatic children. Further, broad antibody responses and genetically diverse infections, in combination, were more strongly associated with protection against malaria than they were individually suggesting that multicomponent malaria vaccines mimicking naturally acquired immunity should ideally induce antibody responses that can be boosted by natural infections.The inhibitory activity of naturally acquired antibodies on the in vitro growth of P. falciparum in relation to merozoite invasion phenotype was investigated in a case-control study in Tanzanian children. The growth-inhibitory activities (GIA) of plasma were different when tested on different parasite lines. The association between GIA and protection against clinical malaria was also parasite line-dependent thus emphasizing the importance of invasion phenotypes as well as the need to consider the choice of parasite lines in the use of GIA as a correlate of protection against clinical malaria in epidemiological and vaccine studies.Within a longitudinally monitored population in Kenya, temporal dynamics of anti-merozoite antibody responses were investigated in children with different susceptibilities to malaria. Overall, antibody levels were similar in children experiencing multiple episodes or only single episodes suggesting that differences in disease susceptibility are not attributable to differences in the acquisition of anti-merozoite antibody responses, and may be explained by other factors, such as differences in the intensity of exposure to the parasite in this setting of low-moderate malaria transmission.To investigate the longevity of immune responses induced by natural P. falciparum infections, circulating merozoite antigen-specific antibodies and memory B-cells (MBCs) were studied in travelers who had been diagnosed and treated for malaria in Stockholm 1-16 years previously. P. falciparum-specific MBCs, but not antibodies, were found to have been maintained for up to 16 years without re-exposure to the parasite.In conclusion, single natural P. falciparum infections induce long-lived memory-B cell responses to merozoite antigens, however, broad and protective antibody responses require repeated exposure and preferably persistent genetically diverse infections to confer clinical immunity to malaria. Taken together, these studies advance the understanding of naturally acquired immunity to malaria and have important implications for the development of malaria vaccines.List of scientific papersI. Josea Rono, Faith H. A. Osier, Daniel Olsson, Scott Montgomery, Leah Mhoja, Ingegerd Rooth, Kevin Marsh and Anna Färnert. Breadth of anti-merozoite antibody responses is associated with the genetic diversity of symptomatic Plasmodium falciparum infections and protection against clinical malaria. Clinical Infectious Diseases. 2013 Sep 24. [Epub ahead of print] https://doi.org/10.1093/cid/cit556 II. Josea Rono, Anna Färnert, Daniel Olsson, Faith Osier, Ingegerd Rooth, Kristina E. M. Persson. Plasmodium falciparum line-dependent association of in vitro growth-inhibitory activity and risk of malaria. Infection and Immunity. 2012 May; 80(5):1900-8. Epub 2012 Mar 5. https://doi.org/10.1128/IAI.06190-11 III. Josea Rono, Anna Färnert, John Ojal, George Nyangweso, Linda Murungi, Gathoni Kamuyu, Juliana Wambua, Ally Olotu, Kevin Marsh, and Faith H. A. Osier Five-year Temporal Dynamics of Naturally Acquired Antibodies to Plasmodium falciparum Merozoite Antigens in Children experiencing Multiple episodes of Malaria. [Manuscript]IV. Francis M Ndungu, Klara Lundblom, Josea Rono, Joseph Illingworth, Sara Eriksson and Anna Färnert. Long-Lived Plasmodium falciparum-Specific Memory B cells in Naturally Exposed Swedish Travelers. European Journal of Immunology. 2013 Jul 23. https://doi.org/10.1002/eji.201343630 </p
Antibody acquisition models: a new tool for serological surveillance of malaria transmission intensity
Get PDFSerology has become an increasingly important tool for the surveillance of a wide range of infectious diseases. It has been particularly useful to monitor malaria transmission in elimination settings where existing metrics such as parasite prevalence and incidence of clinical cases are less sensitive. Seroconversion rates, based on antibody prevalence to Plasmodium falciparum asexual blood-stage antigens, provide estimates of transmission intensity that correlate with entomological inoculation rates but lack precision in settings where seroprevalence is still high. Here we present a new and widely applicable method, based on cross-sectional data on individual antibody levels. We evaluate its use as a sero-surveillance tool in a Tanzanian setting with declining malaria prevalence. We find that the newly developed mathematical models produce more precise estimates of transmission patterns, are robust in high transmission settings and when sample sizes are small, and provide a powerful tool for serological evaluation of malaria transmission intensity
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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