| 1. |
- Niemi, MEK, et al.
(författare)
-
- 2021
-
swepub:Mat__t
|
|
| 2. |
- Kanai, M, et al.
(författare)
-
- 2023
-
swepub:Mat__t
|
|
| 3. |
- Campbell, PJ, et al.
(författare)
-
Pan-cancer analysis of whole genomes
- 2020
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
-
Tidskriftsartikel (refereegranskat)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
|
|
| 4. |
- Weinstein, John N., et al.
(författare)
-
The cancer genome atlas pan-cancer analysis project
- 2013
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:10, s. 1113-1120
-
Forskningsöversikt (refereegranskat)abstract
- The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile. © 2013 Nature America, Inc. All rights reserved.
|
|
| 5. |
- Wulf Hanson, Sarah, et al.
(författare)
-
A global systematic analysis of the occurrence, severity, and recovery pattern of long COVID in 2020 and 2021
- 2022
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Importance: While much of the attention on the COVID-19 pandemic was directed at the daily counts of cases and those with serious disease overwhelming health services, increasingly, reports have appeared of people who experience debilitating symptoms after the initial infection. This is popularly known as long COVID.Objective: To estimate by country and territory of the number of patients affected by long COVID in 2020 and 2021, the severity of their symptoms and expected pattern of recovery.Design: We jointly analyzed ten ongoing cohort studies in ten countries for the occurrence of three major symptom clusters of long COVID among representative COVID cases. The defining symptoms of the three clusters (fatigue, cognitive problems, and shortness of breath) are explicitly mentioned in the WHO clinical case definition. For incidence of long COVID, we adopted the minimum duration after infection of three months from the WHO case definition. We pooled data from the contributing studies, two large medical record databases in the United States, and findings from 44 published studies using a Bayesian meta-regression tool. We separately estimated occurrence and pattern of recovery in patients with milder acute infections and those hospitalized. We estimated the incidence and prevalence of long COVID globally and by country in 2020 and 2021 as well as the severity-weighted prevalence using disability weights from the Global Burden of Disease study.Results: Analyses are based on detailed information for 1906 community infections and 10526 hospitalized patients from the ten collaborating cohorts, three of which included children. We added published data on 37262 community infections and 9540 hospitalized patients as well as ICD-coded medical record data concerning 1.3 million infections. Globally, in 2020 and 2021, 144.7 million (95% uncertainty interval [UI] 54.8-312.9) people suffered from any of the three symptom clusters of long COVID. This corresponds to 3.69% (1.38-7.96) of all infections. The fatigue, respiratory, and cognitive clusters occurred in 51.0% (16.9-92.4), 60.4% (18.9-89.1), and 35.4% (9.4-75.1) of long COVID cases, respectively. Those with milder acute COVID-19 cases had a quicker estimated recovery (median duration 3.99 months [IQR 3.84-4.20]) than those admitted for the acute infection (median duration 8.84 months [IQR 8.10-9.78]). At twelve months, 15.1% (10.3-21.1) continued to experience long COVID symptoms.Conclusions and relevance: The occurrence of debilitating ongoing symptoms of COVID-19 is common. Knowing how many people are affected, and for how long, is important to plan for rehabilitative services and support to return to social activities, places of learning, and the workplace when symptoms start to wane.Key Points: Question: What are the extent and nature of the most common long COVID symptoms by country in 2020 and 2021?Findings: Globally, 144.7 million people experienced one or more of three symptom clusters (fatigue; cognitive problems; and ongoing respiratory problems) of long COVID three months after infection, in 2020 and 2021. Most cases arose from milder infections. At 12 months after infection, 15.1% of these cases had not yet recovered.Meaning: The substantial number of people with long COVID are in need of rehabilitative care and support to transition back into the workplace or education when symptoms start to wane.
|
|
| 6. |
- Wulf Hanson, Sarah, et al.
(författare)
-
Estimated Global Proportions of Individuals With Persistent Fatigue, Cognitive, and Respiratory Symptom Clusters Following Symptomatic COVID-19 in 2020 and 2021
- 2022
-
Ingår i: Journal of the American Medical Association (JAMA). - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 328:16, s. 1604-1615
-
Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: Some individuals experience persistent symptoms after initial symptomatic SARS-CoV-2 infection (often referred to as Long COVID).OBJECTIVE: To estimate the proportion of males and females with COVID-19, younger or older than 20 years of age, who had Long COVID symptoms in 2020 and 2021 and their Long COVID symptom duration.DESIGN, SETTING, AND PARTICIPANTS: Bayesian meta-regression and pooling of 54 studies and 2 medical record databases with data for 1.2 million individuals (from 22 countries) who had symptomatic SARS-CoV-2 infection. Of the 54 studies, 44 were published and 10 were collaborating cohorts (conducted in Austria, the Faroe Islands, Germany, Iran, Italy, the Netherlands, Russia, Sweden, Switzerland, and the US). The participant data were derived from the 44 published studies (10 501 hospitalized individuals and 42 891 nonhospitalized individuals), the 10 collaborating cohort studies (10 526 and 1906), and the 2 US electronic medical record databases (250 928 and 846 046). Data collection spanned March 2020 to January 2022.EXPOSURES: Symptomatic SARS-CoV-2 infection.MAIN OUTCOMES AND MEASURES: Proportion of individuals with at least 1 of the 3 self-reported Long COVID symptom clusters (persistent fatigue with bodily pain or mood swings; cognitive problems; or ongoing respiratory problems) 3 months after SARS-CoV-2 infection in 2020 and 2021, estimated separately for hospitalized and nonhospitalized individuals aged 20 years or older by sex and for both sexes of nonhospitalized individuals younger than 20 years of age.RESULTS: A total of 1.2 million individuals who had symptomatic SARS-CoV-2 infection were included (mean age, 4-66 years; males, 26%-88%). In the modeled estimates, 6.2% (95% uncertainty interval [UI], 2.4%-13.3%) of individuals who had symptomatic SARS-CoV-2 infection experienced at least 1 of the 3 Long COVID symptom clusters in 2020 and 2021, including 3.2% (95% UI, 0.6%-10.0%) for persistent fatigue with bodily pain or mood swings, 3.7% (95% UI, 0.9%-9.6%) for ongoing respiratory problems, and 2.2% (95% UI, 0.3%-7.6%) for cognitive problems after adjusting for health status before COVID-19, comprising an estimated 51.0% (95% UI, 16.9%-92.4%), 60.4% (95% UI, 18.9%-89.1%), and 35.4% (95% UI, 9.4%-75.1%), respectively, of Long COVID cases. The Long COVID symptom clusters were more common in women aged 20 years or older (10.6% [95% UI, 4.3%-22.2%]) 3 months after symptomatic SARS-CoV-2 infection than in men aged 20 years or older (5.4% [95% UI, 2.2%-11.7%]). Both sexes younger than 20 years of age were estimated to be affected in 2.8% (95% UI, 0.9%-7.0%) of symptomatic SARS-CoV-2 infections. The estimated mean Long COVID symptom cluster duration was 9.0 months (95% UI, 7.0-12.0 months) among hospitalized individuals and 4.0 months (95% UI, 3.6-4.6 months) among nonhospitalized individuals. Among individuals with Long COVID symptoms 3 months after symptomatic SARS-CoV-2 infection, an estimated 15.1% (95% UI, 10.3%-21.1%) continued to experience symptoms at 12 months.CONCLUSIONS AND RELEVANCE: This study presents modeled estimates of the proportion of individuals with at least 1 of 3 self-reported Long COVID symptom clusters (persistent fatigue with bodily pain or mood swings; cognitive problems; or ongoing respiratory problems) 3 months after symptomatic SARS-CoV-2 infection.
|
|
| 7. |
- Ally, M., et al.
(författare)
-
Cross-sectional and longitudinal evaluation of plasma glial fibrillary acidic protein to detect and predict clinical syndromes of Alzheimer's disease
- 2023
-
Ingår i: Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring. - 2352-8729. ; 15:4
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: This study examined plasma glial fibrillary acidic protein (GFAP) as a biomarker of cognitive impairment due to Alzheimer's disease (AD) with and against plasma neurofilament light chain (NfL), and phosphorylated tau (p-tau)181+231.Methods: Plasma samples were analyzed using Simoa platform for 567 participants spanning the AD continuum. Cognitive diagnosis, neuropsychological testing, and dementia severity were examined for cross-sectional and longitudinal outcomes.Results: Plasma GFAP discriminated AD dementia from normal cognition (adjusted mean difference = 0.90 standard deviation [SD]) and mild cognitive impairment (adjusted mean difference = 0.72 SD), and demonstrated superior discrimination compared to alternative plasma biomarkers. Higher GFAP was associated with worse dementia severity and worse performance on 11 of 12 neuropsychological tests. Longitudinally, GFAP predicted decline in memory, but did not predict conversion to mild cognitive impairment or dementia.Discussion: Plasma GFAP was associated with clinical outcomes related to suspected AD and could be of assistance in a plasma biomarker panel to detect in vivo AD.
|
|
| 8. |
- Hawkins, Stephen J., et al.
(författare)
-
The Intertidal Zone of the North-East Atlantic Region
- 2019
-
Ingår i: Interactions in the Marine Benthos: Global Patterns and Processes (Systematics Association Special Volume Series, pp. 7-46). - : Cambridge university press. - 9781108416085
-
Bokkapitel (refereegranskat)abstract
- The rocky shores of the north-east Atlantic have been long studied. Our focus is from Gibraltar to Norway plus the Azores and Iceland. Phylogeographic processes shape biogeographic patterns of biodiversity. Long-term and broadscale studies have shown the responses of biota to past climate fluctuations and more recent anthropogenic climate change. Inter- and intra-specific species interactions along sharp local environmental gradients shape distributions and community structure and hence ecosystem functioning. Shifts in domination by fucoids in shelter to barnacles/mussels in exposure are mediated by grazing by patellid limpets. Further south fucoids become increasingly rare, with species disappearing or restricted to estuarine refuges, caused by greater desiccation and grazing pressure. Mesoscale processes influence bottom-up nutrient forcing and larval supply, hence affecting species abundance and distribution, and can be proximate factors setting range edges (e.g., the English Channel, the Iberian Peninsula). Impacts of invasive non-native species are reviewed. Knowledge gaps such as the work on rockpools and host–parasite dynamics are also outlined.
|
|
| 9. |
|
|
| 10. |
|
|
| 11. |
|
|
| 12. |
|
|
| 13. |
|
|
| 14. |
- Ally, M., et al.
(författare)
-
Learner use of learning objects
- 2005
-
Konferensbidrag (refereegranskat)abstract
- This article reports findings from a study exploring the generativity (Gibbons, Nelson, & Richards, 2000; Parrish, 2004) and discoverability (Friesen, 2001) of learning objects in the hands of the learner. Through the convergence of two separate pilot projects—the Canadian EduSource initiative through Athabasca University, and the researchers’ ongoing study of affective learning in online learning environments (Cleveland-Innes & Ally, 2004)—learner perspectives of learning object use and value was evaluated. Participants in the study of affective outcomes in the workplace worked independently with learning objects and outlined the interaction with learning object repositories and individual learning objects. Analysis of learners’ activity and response indicates that selection of learning object repositories and objects is based on personal needs and expectations for satisfying desired learning outcomes. Data analysis found pedagogical and contextual implications of learning object technology from the point of view of the learner. Results suggest that there is opportunity to combine learning object technology with consideration for learner engagement in designs that support lifelong learning principles and focus on learner development rather than the content or the technology. Cet article nous fait part des résultats d’une ́étude explorant la générativité (Gibbons, Nelson, & Richards, 2000; Parrish, 2004) et la facilité à trouver (Friesen, 2001) des objets d’apprentissage entre les mains des apprenants. Grace à la convergence de deux projets pilotes distincts—l’initiative EduSource de l’Université Athabasca, et l’étude en cours des auteurs de l’apprentissage affectif dans des environnements d’apprentissage en ligne (Cleveland-Innes & Ally, 2004)—la perspective des apprenants à propos de l’utilisation et de la valeur des objets d’apprentissage a été évalué. Les participants à l’étude sur les conséquences affectives en milieu de travail ont utilisé des objets d’apprentissage de manière indépendante et ont souligné l’interaction entre les dépôts d’objets et les objets d’apprentissage individuels. L’analyse de l’activité et de la réponse des apprenants indique que le choix des dépôts d’objets d’apprentissage et des objets eux-memes est basé sur les besoins personnels et les attentes de l’apprenant sur les capacités des objets à satisfaire les besoins d’apprentissage. L’analyse des données a permis d’identifier des conséquences pé́dagogiques et contextuelles de la technologie derrière les objets d’apprentissage, du point de vue de l’apprenant. Les résultats suggèrent qu’il y a une opportunité de combiner la technologie soutenant les objets d’apprentissage et une péoccupation pour l’engagement de l’apprenant grâce à des designs qui soutiennent les principes de l’apprentissage à vie et se centrent sur le développement de l’apprenant plutôt que sur le contenu de la technologie.
|
|
| 15. |
|
|
| 16. |
- Ambele, Raiton Malema, et al.
(författare)
-
A review of the Development Trend of Personalized learning Technologies and its Applications
- 2022
-
Ingår i: International Journal of Advances in Scientific Research and Engineering. - : Sretechjournal Publication. - 2454-8006. ; 8:11, s. 75-91
-
Tidskriftsartikel (refereegranskat)abstract
- Personalized learning tailors material and strategy to student requirements, interests, and goals in e-learning. These developments help educational institutions and other organizations to keep up with the fast pace of information technology, communications, and computing power. Studies show that self-adaptive learning and relevant learning information improve study efficiency. Compared to traditional teaching methods, the practice of online education is well in its infancy. On the other hand, the pedagogy and evaluation of students in online courses have a large gap that has to be filled, necessitating significant improvements in e-learning. We call this approach to education "personalized learning," which is a central focus of today's leading online education platforms. Several studies have been conducted on e-learning and personalized learning, but few investigated the development trend of personalized learning technologies and applications. Therefore this study examines the literature to close the gap and promote the development trend for personalized learning technologies and applications in higher education from 2010 to 2021 by analyzing related journal articles. The pivotal studies used inclusion criteria after a search generated 372 complete research articles and reduced them to 146 publications based on their proposed learning domains and research themes. Through carefully reviewing current trends and successes in numerous aspects of personalized learning, this discussion analyzes prospective future research directions in the field of personalized learning.
|
|
| 17. |
- Bakari, Catherine, et al.
(författare)
-
Trends of Plasmodium falciparum molecular markers associated with resistance to artemisinins and reduced susceptibility to lumefantrine in Mainland Tanzania from 2016 to 2021
- 2024
-
Ingår i: MALARIA JOURNAL. - 1475-2875. ; 23:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background Therapeutic efficacy studies (TESs) and detection of molecular markers of drug resistance are recommended by the World Health Organization (WHO) to monitor the efficacy of artemisinin-based combination therapy (ACT). This study assessed the trends of molecular markers of artemisinin resistance and/or reduced susceptibility to lumefantrine using samples collected in TES conducted in Mainland Tanzania from 2016 to 2021. Methods A total of 2,015 samples were collected during TES of artemether-lumefantrine at eight sentinel sites (in Kigoma, Mbeya, Morogoro, Mtwara, Mwanza, Pwani, Tabora, and Tanga regions) between 2016 and 2021. Photo-induced electron transfer polymerase chain reaction (PET-PCR) was used to confirm presence of malaria parasites before capillary sequencing, which targeted two genes: Plasmodium falciparum kelch 13 propeller domain (k13) and P. falciparum multidrug resistance 1 (pfmdr1). Results Sequencing success was >= 87.8%, and 1,724/1,769 (97.5%) k13 wild-type samples were detected. Thirty-seven (2.1%) samples had synonymous mutations and only eight (0.4%) had non-synonymous mutations in the k13 gene; seven of these were not validated by the WHO as molecular markers of resistance. One sample from Morogoro in 2020 had a k13 R622I mutation, which is a validated marker of artemisinin partial resistance. For pfmdr1, all except two samples carried N86 (wild-type), while mutations at Y184F increased from 33.9% in 2016 to about 60.5% in 2021, and only four samples (0.2%) had D1246Y mutations. pfmdr1 haplotypes were reported in 1,711 samples, with 985 (57.6%) NYD, 720 (42.1%) NFD, and six (0.4%) carrying minor haplotypes (three with NYY, 0.2%; YFD in two, 0.1%; and NFY in one sample, 0.1%). Between 2016 and 2021, NYD decreased from 66.1% to 45.2%, while NFD increased from 38.5% to 54.7%. Conclusion This is the first report of the R622I (k13 validated mutation) in Tanzania. N86 and D1246 were nearly fixed, while increases in Y184F mutations and NFD haplotype were observed between 2016 and 2021. Despite the reports of artemisinin partial resistance in Rwanda and Uganda, this study did not report any other validated mutations in these study sites in Tanzania apart from R622I suggesting that intensified surveillance is urgently needed to monitor trends of drug resistance markers and their impact on the performance of ACT.
|
|
| 18. |
|
|
| 19. |
|
|
| 20. |
- Cleveland-Innes, Marta, et al.
(författare)
-
Athabasca University eduSource project : Building an accessible learning object repository
- 2005
-
Ingår i: Australasian Journal of Educational Technology. - 1449-3098 .- 1449-5554. ; 21:5, s. 367-381
-
Tidskriftsartikel (refereegranskat)abstract
- Athabasca University - Canada's Open University (AU) made the commitment to put all of its courses online as part of its Strategic University Plan. In pursuit of this goal, AU participated in the eduSource project, a pan-Canadian effort to build the infrastructure for an interoperable network of learning object repositories. AU acted as a leader in the eduSource work package, responsible for the metadata and standards for learning objects. In addition, the team of professionals, academics, librarians and other researchers worked to create an accessible repository of learning objects across university departments and subjects. Most critically, the team worked beyond the development of a learning object repository and considered the adaptation of content and related applications, pedagogical approaches and the use of learning objects by instructional designers, faculty and the learners themselves. This paper describes one institution's approach to learning object repository development, from a technical and pedagogical perspective, along with some of the lessons learned during the process.
|
|
| 21. |
- Cleveland-Innes, Marta, et al.
(författare)
-
Learning to feel : Education, affective outcomes and the use of online teaching and learning
- 2006
-
Konferensbidrag (refereegranskat)abstract
- Research employing an experimental design pilot tested two delivery platforms, WebCT and ElluminateLive, for the generation of affective learning outcomes in the workplace. Ten different organizations across Western Canada asked their call centre/help desk staff to participate in an online course on customer service. One hundred and one participants were randomly assigned to two types of online learning management systems. Data comparing results of the two groups are inconclusive in relation to delivery outcomes, but indicate there is potential for soft skill development and affective gain using online delivery. Both groups performed well on tests of knowledge regarding appropriate affect in customer service environments. Soft skill assessment showed small gains from time one to time two for participants studying in both platforms. Differences between groups were seen in two observations. There was greater engagement and interaction among participants in the WebCT group. Additionally, the WebCT group yielded higher exam scores, but differences between exam means were not statistically significant.
|
|
| 22. |
- Cleveland-Innes, Marta, et al.
(författare)
-
Learning to feel : Education, affective outcomes and the use of online teaching and learning
- 2009
-
Ingår i: European Journal of Open, Distance and E-Learning. - 1027-5207. ; 2
-
Tidskriftsartikel (refereegranskat)abstract
- Research employing an experimental design pilot tested two delivery platforms, WebCT and ElluminateLive, for the generation of affective learning outcomes in the workplace. Ten different organizations across Western Canada asked their call centre/help desk staff to participate in an online course on customer service. One hundred and one participants were randomly assigned to two types of online learning management systems. Data comparing results of the two groups are inconclusive in relation to delivery outcomes, but indicate there is potential for soft skill development and affective gain using online delivery. Both groups performed well on tests of knowledge regarding appropriate affect in customer service environments. Soft skill assessment showed small gains from time one to time two for participants studying in both platforms. Differences between groups were seen in two observations. There was greater engagement and interaction among participants in the WebCT group. Additionally, the WebCT group yielded higher exam scores, but differences between exam means were not statistically significant.
|
|
| 23. |
|
|
| 24. |
|
|
| 25. |
|
|
| 26. |
- Ishengoma, Deus S., et al.
(författare)
-
Efficacy and safety of artemether-lumefantrine for the treatment of uncomplicated malaria and prevalence of Pfk13 and Pfmdr1 polymorphisms after a decade of using artemisinin-based combination therapy in mainland Tanzania
- 2019
-
Ingår i: Malaria Journal. - : BMC. - 1475-2875. ; 18
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The World Health Organization recommends regular therapeutic efficacy studies (TES) to monitor the performance of first and second-line anti-malarials. In 2016, efficacy and safety of artemether-lumefantrine (AL) for the treatment of uncomplicated falciparum malaria were assessed through a TES conducted between April and October 2016 at four sentinel sites of Kibaha, Mkuzi, Mlimba, and Ujiji in Tanzania. The study also assessed molecular markers of artemisinin and lumefantrine (partner drug) resistance.Methods: Eligible patients were enrolled at the four sites, treated with standard doses of AL, and monitored for 28 days with clinical and laboratory assessments. The main outcomes were PCR corrected cure rates, day 3 positivity rates, safety of AL, and prevalence of single nucleotide polymorphisms in Plasmodium falciparum kelch 13 (Pfk13) (codon positions: 440-600) and P. falciparum multi-drug resistance 1 (Pfmdr1) genes (codons: N86Y, Y184F and D1246Y), markers of artemisinin and lumefantrine resistance, respectively.Results: Of 344 patients enrolled, three withdrew, six were lost to follow-up; and results were analysed for 335 (97.4%) patients. Two patients had treatment failure (one early treatment failure and one recrudescent infection) after PCR correction, yielding an adequate clinical and parasitological response of > 98%. Day 3 positivity rates ranged from 0 to 5.7%. Common adverse events included cough, abdominal pain, vomiting, and diarrhoea. Two patients had serious adverse events; one died after the first dose of AL and another required hospitalization after the second dose of AL (on day 0) but recovered completely. Of 344 samples collected at enrolment (day 0), 92.7% and 100% were successfully sequenced for Pfk13 and Pfmdr1 genes, respectively. Six (1.9%) had non-synonymous mutations in Pfk13, none of which had been previously associated with artemisinin resistance. For Pfmdr1, the NFD haplotype (codons N86, 184F and D1246) was detected in 134 (39.0%) samples; ranging from 33.0% in Mlimba to 45.5% at Mkuzi. The difference among the four sites was not significant (p = 0.578). All samples had a single copy of the Pfmdr1 gene.Conclusion: The study indicated high efficacy of AL and the safety profile was consistent with previous reports. There were no known artemisinin-resistance Pfk13 mutations, but there was a high prevalence of a Pfmdr1 haplotype associated with reduced sensitivity to lumefantrine (but no reduced efficacy was observed in the subjects). Continued TES and monitoring of markers of resistance to artemisinin and partner drugs is critical for early detection of resistant parasites and to inform evidence-based malaria treatment policies.
|
|
| 27. |
- Ishengoma, Deus S., et al.
(författare)
-
Microsatellites reveal high polymorphism and high potential for use in anti-malarial efficacy studies in areas with different transmission intensities in mainland Tanzania
- 2024
-
Ingår i: MALARIA JOURNAL. - : Springer Nature. - 1475-2875. ; 23:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background Tanzania is currently implementing therapeutic efficacy studies (TES) in areas of varying malaria transmission intensities as per the World Health Organization (WHO) recommendations. In TES, distinguishing reinfection from recrudescence is critical for the determination of anti-malarial efficacy. Recently, the WHO recommended genotyping polymorphic coding genes, merozoite surface proteins 1 and 2 (msp1 and msp2), and replacing the glutamate-rich protein (glurp) gene with one of the highly polymorphic microsatellites in Plasmodium falciparum to adjust the efficacy of antimalarials in TES. This study assessed the polymorphisms of six neutral microsatellite markers and their potential use in TES, which is routinely performed in Tanzania. Methods Plasmodium falciparum samples were obtained from four TES sentinel sites, Kibaha (Pwani), Mkuzi (Tanga), Mlimba (Morogoro) and Ujiji (Kigoma), between April and September 2016. Parasite genomic DNA was extracted from dried blood spots on filter papers using commercial kits. Genotyping was done using six microsatellites (Poly-alpha, PfPK2, TA1, C3M69, C2M34 and M2490) by capillary method, and the data were analysed to determine the extent of their polymorphisms and genetic diversity at the four sites. Results Overall, 83 (88.3%) of the 94 samples were successfully genotyped (with positive results for >= 50.0% of the markers), and > 50.0% of the samples (range = 47.6-59.1%) were polyclonal, with a mean multiplicity of infection (MOI) ranging from 1.68 to 1.88 among the four sites. There was high genetic diversity but limited variability among the four sites based on mean allelic richness (R-S = 7.48, range = 7.27-8.03, for an adjusted minimum sample size of 18 per site) and mean expected heterozygosity (H-e = 0.83, range = 0.80-0.85). Cluster analysis of haplotypes using STRUCTURE, principal component analysis, and pairwise genetic differentiation (F-ST) did not reveal population structure or clustering of parasites according to geographic origin. Of the six markers, Poly-alpha was the most polymorphic, followed by C2M34, TA1 and C3M69, while M2490 was the least polymorphic. Conclusion Microsatellite genotyping revealed high polyclonality and genetic diversity but no significant population structure. Poly-alpha, C2M34, TA1 and C3M69 were the most polymorphic markers, and Poly-alpha alone or with any of the other three markers could be adopted for use in TES in Tanzania.
|
|
