Author
Steve M. Taylor
Other affiliations: Durham University, Malawi-Liverpool-Wellcome Trust Clinical Research Programme, University of California, San Francisco ...read more
Bio: Steve M. Taylor is an academic researcher from Duke University. The author has contributed to research in topics: Malaria & Plasmodium falciparum. The author has an hindex of 30, co-authored 91 publications receiving 2727 citations. Previous affiliations of Steve M. Taylor include Durham University & Malawi-Liverpool-Wellcome Trust Clinical Research Programme.
Topics: Malaria, Plasmodium falciparum, Sulfadoxine, Population, Pregnancy
Papers published on a yearly basis
Papers
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TL;DR: Haemoglobin AS, CC, and AC genotypes and homozygous and heterozygous α-thalassaemia provide significant protection from severe malaria syndromes, but these haemoglobinopathies differ substantially in the degree of protection provided and confer mild or no protection against uncomplicated malaria and asymptomatic parasitaemia.
Abstract: Summary Background Haemoglobinopathies can reduce the risk of malaria syndromes. We aimed to quantify the relation between different haemoglobin mutations and malaria protection to strengthen the foundation for translational studies of malaria pathogenesis and immunity. Methods We systematically searched the Medline and Embase databases for studies that estimated the risk of malaria in patients with and without haemoglobinopathies up to Sept 9, 2011, and identified additional studies from reference lists. We included studies that enrolled mainly children or pregnant women and had the following outcomes: Plasmodium falciparum severe malaria, uncomplicated malaria, asymptomatic parasitaemia, or pregnancy-associated malaria, and Plasmodium vivax malaria. Two reviewers identified studies independently, assessed quality of the studies, and extracted data. We produced odds ratios (ORs; 95% CIs) for case-control studies and incidence rate ratios (IRRs; 95% CIs) for prospective studies. We did the meta-analysis with a random-effects model when equivalent outcomes were reported in more than one study. Findings Of 62 identified studies, 44 reported data for haemoglobin AS, 19 for haemoglobin AC and CC, and 18 for α-thalassaemia. Meta-analysis of case-control studies showed a decreased risk of severe P falciparum malaria in individuals with haemoglobin AS (OR 0·09, 95% CI 0·06–0·12), haemoglobin CC (0·27, 0·11–0·63), haemoglobin AC (0·83, 0·67–0·96), homozygous α-thalassaemia (0·63, 0·48–0·83), and heterozygous α-thalassaemia (0·83, 0·74–0·92). In meta-analysis of prospective trials only haemoglobin AS was consistently associated with protection from uncomplicated malaria (IRR 0·69, 95% CI 0·61–0·79); no haemoglobinopathies led to consistent protection from asymptomatic parasitaemia. Few clinical studies have investigated β-thalassaemia, haemoglobin E, P vivax malaria, or pregnancy-associated malaria. Interpretation Haemoglobin AS, CC, and AC genotypes and homozygous and heterozygous α-thalassaemia provide significant protection from severe malaria syndromes, but these haemoglobinopathies differ substantially in the degree of protection provided and confer mild or no protection against uncomplicated malaria and asymptomatic parasitaemia. Through attenuation of severity of malaria, haemoglobinopathies could serve as a model for investigation of the mechanisms of malaria pathogenesis and immunity. Funding US National Institute of Allergy and Infectious Diseases.
255 citations
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Duke University1, University of North Carolina at Chapel Hill2, Liverpool School of Tropical Medicine3, University of Ouagadougou4, University of London5, Kwame Nkrumah University of Science and Technology6, Medical Research Council7, Centers for Disease Control and Prevention8, Kenya Medical Research Institute9, University of Malawi10, Karolinska Institutet11, University of Health and Allied Sciences12, University of California, San Francisco13, University of Kinshasa14, University of Massachusetts Amherst15
TL;DR: An assay to quantify rare polymorphisms in parasite populations that uses a pooled deep-sequencing approach to score allele frequencies is developed and validated by evaluating mixtures of laboratory parasite strains, and used to screen P. falciparum parasites from >1100 African infections collected since 2002.
Abstract: Plasmodium falciparum parasites that are resistant to artemisinins have been detected in Southeast Asia. Resistance is associated with several polymorphisms in the parasite's K13-propeller gene. The molecular epidemiology of these artemisinin resistance genotypes in African parasite populations is unknown. We developed an assay to quantify rare polymorphisms in parasite populations that uses a pooled deep-sequencing approach to score allele frequencies, validated it by evaluating mixtures of laboratory parasite strains, and then used it to screen P. falciparum parasites from >1100 African infections collected since 2002 from 14 sites across sub-Saharan Africa. We found no mutations in African parasite populations that are associated with artemisinin resistance in Southeast Asian parasites. However, we observed 15 coding mutations, including 12 novel mutations, and limited allele sharing between parasite populations, consistent with a large reservoir of naturally occurring K13-propeller variation. Although polymorphisms associated with artemisinin resistance in P. falciparum in Southeast Asia are not prevalent in sub-Saharan Africa, numerous K13-propeller coding polymorphisms circulate in Africa. Although their distributions do not support a widespread selective sweep for an artemisinin-resistant phenotype, the impact of these mutations on artemisinin susceptibility is unknown and will require further characterization. Rapid, scalable molecular surveillance offers a useful adjunct in tracking and containing artemisinin resistance.
253 citations
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TL;DR: This Series paper summarises recent progress and highlights unresolved issues related to the burden of malaria in pregnancy and suggests pregnant women could be used to monitor malaria transmission.
Abstract: Over the past 10 years, knowledge of the burden, economic costs, and consequences of malaria in pregnancy has improved, and the prevalence of malaria caused by Plasmodium falciparum has declined substantially in some geographical areas. In particular, studies outside of Africa have increased the evidence base of Plasmodium vivax in pregnancy. Rapid diagnostic tests have been poor at detecting malaria in pregnant women, while PCR has shown a high prevalence of low density infection, the clinical importance of which is unknown. Erythrocytes infected with P falciparum that express the surface protein VAR2CSA accumulate in the placenta, and VAR2CSA is an important target of protective immunity. Clinical trials for a VAR2CSA vaccine are ongoing, but sequence variation needs to be carefully studied. Health system and household costs still limit access to prevention and treatment services. Within the context of malaria elimination, pregnant women could be used to monitor malaria transmission. This Series paper summarises recent progress and highlights unresolved issues related to the burden of malaria in pregnancy.
193 citations
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TL;DR: This study describes the application of a resource-conserving testing algorithm employing sample pooling for real-time PCR assays for malaria in a cohort of 182 pregnant women in Kinshasa and highlights both substantial discordance between malaria diagnostics and the utility and parsimony of employing a sample Pooling strategy for molecular diagnostics in clinical and epidemiologic malaria studies.
Abstract: Molecular assays can provide critical information for malaria diagnosis, speciation, and drug resistance, but their cost and resource requirements limit their application to clinical malaria studies. This study describes the application of a resource-conserving testing algorithm employing sample pooling for real-time PCR assays for malaria in a cohort of 182 pregnant women in Kinshasa. A total of 1,268 peripheral blood samples were collected during the study. Using a real-time PCR assay that detects all Plasmodium species, microscopy-positive samples were amplified individually; the microscopy-negative samples were amplified after pooling the genomic DNA (gDNA) of four samples prior to testing. Of 176 microscopy-positive samples, 74 were positive by the real-time PCR assay; the 1,092 microscopy-negative samples were initially amplified in 293 pools, and subsequently, 35 samples were real-time PCR positive (3%). With the real-time PCR result as the referent standard, microscopy was 67.9% sensitive (95% confidence interval [CI], 58.3% to 76.5%) and 91.2% specific (95% CI, 89.4% to 92.8%) for malaria. In total, we detected 109 parasitemias by real-time PCR and, by pooling samples, obviated over 50% of reactions and halved the cost of testing. Our study highlights both substantial discordance between malaria diagnostics and the utility and parsimony of employing a sample pooling strategy for molecular diagnostics in clinical and epidemiologic malaria studies.
153 citations
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Kenya Medical Research Institute1, Centers for Disease Control and Prevention2, University of North Carolina at Chapel Hill3, Duke University4, Liverpool School of Tropical Medicine5, University of the Sciences6, University of Ouagadougou7, University of Malawi8, New York University9, University of Copenhagen10
TL;DR: The efficacy of SP to clear peripheral parasites and prevent new infections during pregnancy is compromised in areas with >90% prevalence of Pfdhps-K540E, and in these high-resistance areas, IPTp-SP use remains associated with increases in birth weight and maternal hemoglobin.
Abstract: Background:
Owing to increasing sulfadoxine-pyrimethamine (SP) resistance in sub-Saharan Africa, monitoring the effectiveness of intermittent preventive therapy in pregnancy (IPTp) with SP is crucial.
Methods:
Between 2009 and 2013, both the efficacy of IPTp-SP at clearing existing peripheral malaria infections and the effectiveness of IPTp-SP at reducing low birth weight (LBW) were assessed among human immunodeficiency virus–uninfected participants in 8 sites in 6 countries. Sites were classified as high, medium, or low resistance after measuring parasite mutations conferring SP resistance. An individual-level prospective pooled analysis was conducted.
Results:
Among 1222 parasitemic pregnant women, overall polymerase chain reaction–uncorrected and –corrected failure rates by day 42 were 21.3% and 10.0%, respectively (39.7% and 21.1% in high-resistance areas; 4.9% and 1.1% in low-resistance areas). Median time to recurrence decreased with increasing prevalence of Pfdhps-K540E. Among 6099 women at delivery, IPTp-SP was associated with a 22% reduction in the risk of LBW (prevalence ratio [PR], 0.78; 95% confidence interval [CI], .69–.88; P < .001). This association was not modified by insecticide-treated net use or gravidity, and remained significant in areas with high SP resistance (PR, 0.81; 95% CI, .67–.97; P = .02).
Conclusions:
The efficacy of SP to clear peripheral parasites and prevent new infections during pregnancy is compromised in areas with >90% prevalence of Pfdhps-K540E. Nevertheless, in these high-resistance areas, IPTp-SP use remains associated with increases in birth weight and maternal hemoglobin. The effectiveness of IPTp in eastern and southern Africa is threatened by further increases in SP resistance and reinforces the need to evaluate alternative drugs and strategies for the control of malaria in pregnancy.
123 citations
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TL;DR: It is suggested that the natural selection against large insertion/deletion is so weak that a large amount of variation is maintained in a population.
11,521 citations
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Donostia International Physics Center1, Rovira i Virgili University2, Victoria University of Wellington3, MacDiarmid Institute for Advanced Materials and Nanotechnology4, University of Cambridge5, University of California, Santa Barbara6, Queen's University Belfast7, Technical University of Denmark8, University of Victoria9, Chung-Ang University10, Leibniz Institute of Photonic Technology11, University of Jena12, Rutgers University13, University of Strathclyde14, University of Liverpool15, University of Iowa16, University of Minnesota17, Heidelberg University18, National Institute of Advanced Industrial Science and Technology19, Chalmers University of Technology20, Humboldt University of Berlin21, University of Michigan22, Jiangnan University23, Stanford University24, Xiamen University25, Ludwig Maximilian University of Munich26, Hokkaido University27, Seoul National University28, University of Illinois at Urbana–Champaign29, Kwansei Gakuin University30, University of Vigo31, Free University of Berlin32, Northwestern University33, University of Duisburg-Essen34, National Research Council35, Indian Institute of Science Education and Research, Thiruvananthapuram36, Duke University37, Northeastern University (China)38, Temple University39, Wuhan University40, Japan Advanced Institute of Science and Technology41, Jilin University42, Ikerbasque43
TL;DR: Prominent authors from all over the world joined efforts to summarize the current state-of-the-art in understanding and using SERS, as well as to propose what can be expected in the near future, in terms of research, applications, and technological development.
Abstract: The discovery of the enhancement of Raman scattering by molecules adsorbed on nanostructured metal surfaces is a landmark in the history of spectroscopic and analytical techniques. Significant experimental and theoretical effort has been directed toward understanding the surface-enhanced Raman scattering (SERS) effect and demonstrating its potential in various types of ultrasensitive sensing applications in a wide variety of fields. In the 45 years since its discovery, SERS has blossomed into a rich area of research and technology, but additional efforts are still needed before it can be routinely used analytically and in commercial products. In this Review, prominent authors from around the world joined together to summarize the state of the art in understanding and using SERS and to predict what can be expected in the near future in terms of research, applications, and technological development. This Review is dedicated to SERS pioneer and our coauthor, the late Prof. Richard Van Duyne, whom we lost during the preparation of this article.
1,768 citations
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TL;DR: Strong correlations between the presence of a mutant allele, in vitro parasite survival rates and in vivo parasite clearance rates indicate that K13-propeller mutations are important determinants of artemisinin resistance.
Abstract: Plasmodium falciparum resistance to artemisinin derivatives in southeast Asia threatens malaria control and elimination activities worldwide. To monitor the spread of artemisinin resistance, a molecular marker is urgently needed. Here, using whole-genome sequencing of an artemisinin-resistant parasite line from Africa and clinical parasite isolates from Cambodia, we associate mutations in the PF3D7_1343700 kelch propeller domain ('K13-propeller') with artemisinin resistance in vitro and in vivo. Mutant K13-propeller alleles cluster in Cambodian provinces where resistance is prevalent, and the increasing frequency of a dominant mutant K13-propeller allele correlates with the recent spread of resistance in western Cambodia. Strong correlations between the presence of a mutant allele, in vitro parasite survival rates and in vivo parasite clearance rates indicate that K13-propeller mutations are important determinants of artemisinin resistance. K13-propeller polymorphism constitutes a useful molecular marker for large-scale surveillance efforts to contain artemisinin resistance in the Greater Mekong Subregion and prevent its global spread.
1,639 citations
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TL;DR: A review of the global nature of the disease, iron homeostasis in normal and iron-deficient states, clinical findings, treatment, and causes of iron-resistant iron deficiency is given in this article.
Abstract: Iron-deficiency anemia is the most common form of anemia in the world This article reviews the global nature of the disease, iron homeostasis in normal and iron-deficient states, clinical findings, treatment, and causes of iron-resistant iron deficiency
987 citations
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TL;DR: Improved understanding of the molecular response of cells and tissues to ionizing radiation and a new appreciation of the exploitable genetic alterations in tumours have led to the development of treatments combining pharmacological interventions with ionizing Radiation that more specifically target either tumour or normal tissue, leading to improvements in efficacy.
Abstract: Radiotherapy is used to treat approximately 50% of all cancer patients, with varying success. The dose of ionizing radiation that can be given to the tumour is determined by the sensitivity of the surrounding normal tissues. Strategies to improve radiotherapy therefore aim to increase the effect on the tumour or to decrease the effects on normal tissues. These aims must be achieved without sensitizing the normal tissues in the first approach and without protecting the tumour in the second approach. Two factors have made such approaches feasible: namely, an improved understanding of the molecular response of cells and tissues to ionizing radiation and a new appreciation of the exploitable genetic alterations in tumours. These have led to the development of treatments combining pharmacological interventions with ionizing radiation that more specifically target either tumour or normal tissue, leading to improvements in efficacy.
916 citations