1,721,420 research outputs found
Infection Dynamics of Plasmodium falciparum in Papua New Guinea
Full text linkMalaria is one of the leading causes of illness and death in Papua New Guinea (PNG), mainly affecting children under 5 years of age. The current first line treatment for uncomplicated malaria is a combination therapy of sulfadoxine-pyrimethamine and chloroquine (CQ) or amodiaquine, however, frequent treatment failures have been reported shortly after its implementation. Drug resistance has mainly been associated with single nucleotide polymorphisms in five different genes. Different studies have indicated that mutations associated with drug resistance incur fitness costs to the parasite in absence of drug pressure. Among these are reports from different countries where a decreasing prevalence of mutations associated with CQ resistance was observed after CQ has been suspended as first line treatment. As it is experimentally difficult to estimate the fitness of Plasmodium parasites, a surrogate marker is needed to quantify fitness costs associated with drug resistance mutations. We hypothesised that the parasites’ survival within the human host can be used as surrogate marker for parasite fitness. In a pilot study we determined the drug resistance-associated haplotypes of parasite clones at 25 loci on 4 marker genes, and compared their prevalence between newly acquired and chronic infections. A reduced frequency of a 7-fold mutated haplotype and increased frequency of a 5-fold mutated haplotype in long term persistent infections indicated an impaired survival of highly mutated parasites and suggested that the duration of infections is a promising marker for parasite fitness that deserved further investigation. A further approach to define duration of infections more precisely was undertaken with samples from a longitudinal field survey in PNG. A cohort of 269 1-4.5 years old children was followed over a period of 16 months. This provided consecutive blood samples collected in 2-monthly follow-up visits plus a blood sample from each morbid episode. All samples were genotyped for the polymorphic marker gene merozoite surface protein 2 (msp2) in order to distinguish individual parasite clones within a host. The persistence of genotypes in consecutive blood samples of each child was determined. Unexpected high numbers of antimalarial treatments given in the course of this study led to a high turn-over rate of parasite clones and prevented the establishment of asymptomatic long-term infections. The shortage of long untreated periods in our study participants hampered the determination of a novel molecular parameter termed “duration of infection” for each individual parasite clone. This parameter could have been useful for modelling the transmission success and fitness of drug resistant versus drug sensitive parasite clones. We concluded that this approach requires a cohort of semi-immune individuals where treatment is given rarely, e.g. older children or adults, where P. falciparum infections less frequently cause morbid episodes. The high incidence of morbidity in our study cohort allowed us to investigate molecular parameters that have an impact on the development of a subsequent clinical episode. We found that in children >3 years, a higher multiplicity of infection (MOI) at baseline reduced the risk of a P. falciparum episode. These results are in agreement with previous reports and support the concept of premunition. Furthermore, we studied the impact of co-infecting Plasmodium species on MOI and found an increased MOI in the presence of a heterologous species. This can be explained by the observation of reduced parasite densities in mixed-species infections, leading to a decreased need for treatment and thus facilitating the accumulation of multiple clones. Our results provide further evidence for interactions among co-infecting P. falciparum clones as well as among co-infecting Plasmodium species. During the 16 months field survey all morbid episodes were treated with Coartem®. Analysis of msp2 genotyping results revealed an unexpected high number of Coartem® treatment failures. After confirmation of recrudescent parasites with 2 additional marker genes and exclusion of host genetic factors to be responsible for treatment failures, the most likely explanation for the frequently observed Coartem® failures was a combination of poor adherence to the treatment regimen and a lack of fat supplementation which is required for absorption of the drug. Our results disagree with findings from a clinical trial reporting Coartem® to be highly effective in PNG. In contrast, our observations from a non-trial setting highlight potential problems of Coartem® usage in routine clinical practice. In the course of this thesis, genotyping techniques for merozoite surface proteins (msp) 1 and 2 were optimized and applied. Using these high resolution typing techniques based on capillary electrophoresis, we investigated the effect of transmission intensity on diversity and complexity of msp1 and msp2 in samples from PNG and Tanzania. We observed a greater MOI and a greater number of distinct alleles in samples from Tanzania. Genetic diversity was greater for msp2 than for msp1. In both these areas of different malaria endemicity msp2 was found to be superior for distinguishing individual parasite clones. The probability of two infections carrying by chance the same msp2 allele was lower than this probability calculated for msp1. Based on the frequency distribution of msp2 alleles and on the distribution of observed numbers of infections, we estimated the true MOI adjusted for the probability of multiple infections sharing the same allele. For our high resolution typing technique this adjustment made little difference to the estimated mean MOI compared to the observed mean MOI. A central aim of this thesis was to measure molecular parameters of infection dynamics. These can be determined from genotyping longitudinal sets of samples. Some of these parameters were successfully determined: MOI, force of infection (FOI), and detectability. Other parameters such as natural elimination rates and persistence of infections could not be determined due to frequent treatments. We estimated detectability of parasite clones based on samples collected 24 hours apart and investigated its impact on the MOI and FOI. Imperfect detection of parasites occurs as a consequence of sequestration or when parasite densities fluctuate around the detection limit. We found that in our study participants detectability was high. This was likely an effect of high parasite densities in children of this age. The benefit of short-term sampling on measures of MOI and FOI was marginal. We concluded that in future studies carried out in this age group, taking repeated samples 24 hours apart has limited benefit and does not justify the additional costs, work load and discomfort for the study participants. This project contributed to our understanding of the infections dynamics of P. falciparum and the interactions between parasites clones and Plasmodium species. We provided further insights into determinants of malaria episodes and highlighted the potential usefulness of the parameter “duration of infection” as surrogate marker to estimate fitness costs of drug resistance. This thesis provided findings that are relevant for malaria control strategies and treatment guidelines
Marcel Tanner, Global Health Specialist “Extraordinaire” Incl Supplementary Materials with Personal Contributions from Renowned Experts
Full text linkMarcel Tanner, President of the Swiss Academy of the Sciences, Director emeritus of the Swiss Tropical and Public Health Institute (Swiss TPH), and Professor of Epidemiology and Medical Parasitology at the University of Basel, Switzerland, is indeed extraordinary, especially when considering the broad set of global health issues covered by his research [...
No Roots, No Fruits: Marcel Tanner’s Scholarly Contribution, Achievements in Capacity Building, and Impact in Global Health
Full text linkOn 1 October 2022, Marcel Tanner celebrated his 70th birthday with his family and friends on the River Rhein in Basel. Trained in epidemiology (Ph.D.) and public health (MPH), Tanner devoted his entire working life to research, teaching, and capacity building. Indeed, he built up productive partnerships, fostered multinational consortia, served on numerous scientific and strategic advisory boards, and contributed measurably to improving people’s health and well-being. We systematically searched the Web of Science Core Collection to identify Tanner’s scholarly contribution and pursued an in-depth analysis of his scientific oeuvre including the main areas of research, pathogens, diseases, and health systems, and the geographical foci of his scholarly activities. Additionally, we examined Tanner’s impact on personal and institutional capacity building in the arena of global health. We also invited a handful of colleagues to describe their experiences while working with Marcel Tanner. What transpires is a considerable breadth and depth of peer-reviewed publications in tropical medicine; epidemiology, environmental, and occupational health; parasitology; and infectious diseases. More than a third of the 622 peer-reviewed articles, the first piece published in 1978, focused on various aspects of the protozoan parasite Plasmodium and the disease it causes: malaria. Tanner trained, taught, and inspired generations of students, scientists, and practitioners all over the world. His unique ability to bring people and institutions together to work in partnership is at the heart of an impactful career in global health
Estimating the burden of malaria : the need for improved surveillance
No full textIvo Mueller, Laurence Slutsker, and Marcel Tanner highlight the importance of using complementary methods to estimate the burden of malaria and call for a renewed focus on efficient malaria surveillanc
Swiss-Chinese Cooperation in Tropical Medicine: The Role of Professor Marcel Tanner
No full textThis paper is in honour of Professor Marcel Tanner, President of the Swiss Academies of Arts and Sciences, and former Director of the Swiss Tropical and Public Health Institute (Swiss TPH), in Basel, Switzerland. In the 30 plus years since his first visit to China in 1989, Professor Tanner has tirelessly promoted research collaboration between Switzerland and China on health and tropical diseases through international meetings, scholar exchange, and training of young scientists. As a contribution to Professor Tanner’s life’s work of collaboration with Chinese scientists, we summarize here ideas conceived, work initiated and major outcomes. His approach, embodied in his flowery expression: “Alps and Himalayas never meet, but Swiss and Chinese can”, marked the occasion in 2013 when Xinhua Co., Ltd., a pharmaceutical company in Shandong of China, agreed to produce tribendimidine, a new remedy for tropical helminth infections, that was the fruit of long-term research by scientists at the Swiss TPH in Basel, and National Institute of Parasitic Diseases (NIPD) in Shanghai. This was neither the first nor the last of Professor Tanner’s forceful, yet diplomatic influence, and we follow in his footprints when continuing in Swiss-Chinese cooperation in tropical medicine
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
Full text link“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
Full text linkWe 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
Full text linkWe 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
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