Author
Sodiomon B. Sirima
Bio: Sodiomon B. Sirima is an academic researcher from University of Oxford. The author has contributed to research in topics: Malaria & Plasmodium falciparum. The author has an hindex of 40, co-authored 157 publications receiving 5265 citations.
Topics: Malaria, Plasmodium falciparum, Malaria vaccine, Medicine, Vaccination
Papers published on a yearly basis
Papers
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Pasteur Institute1, Leiden University Medical Center2, University of Tübingen3, International Centre for Diarrhoeal Disease Research, Bangladesh4, University of Ibadan5, Nangarhar University6, Mahidol University7, Walter and Eliza Hall Institute of Medical Research8, Papua New Guinea Institute of Medical Research9, University of Melbourne10, Mbarara University of Science and Technology11, Médecins Sans Frontières12, World Health Organization13, Jiangsu University14, National Institute of Parasitic Diseases15, Pennsylvania State University16, Cheikh Anta Diop University17, University of Lomé18, University of Douala19, Research Institute for Tropical Medicine20, Oswaldo Cruz Foundation21, University of Gondar22, Chinese Academy of Sciences23, Henry M. Jackson Foundation for the Advancement of Military Medicine24, Institut de recherche pour le développement25, University of Antwerp26, University of Kinshasa27, Thammasat University28, University of Bamako29, Medical University of Vienna30, Medicines for Malaria Venture31, Université Félix Houphouët-Boigny32, University of London33, Eijkman Institute for Molecular Biology34, Southwest University of Visual Arts35, Columbia University36, Paris Descartes University37
TL;DR: In this article, the authors analyzed the K13-propeller sequence polymorphism in 14,037 samples collected in 59 countries in which malaria is endemic and identified 108 nonsynonymous K13 mutations, which showed marked geographic disparity in their frequency and distribution.
Abstract: BACKGROUND:
Recent gains in reducing the global burden of malaria are threatened by the emergence of Plasmodium falciparum resistance to artemisinins. The discovery that mutations in portions of a P. falciparum gene encoding kelch (K13)-propeller domains are the major determinant of resistance has provided opportunities for monitoring such resistance on a global scale.
METHODS:
We analyzed the K13-propeller sequence polymorphism in 14,037 samples collected in 59 countries in which malaria is endemic. Most of the samples (84.5%) were obtained from patients who were treated at sentinel sites used for nationwide surveillance of antimalarial resistance. We evaluated the emergence and dissemination of mutations by haplotyping neighboring loci.
RESULTS:
We identified 108 nonsynonymous K13 mutations, which showed marked geographic disparity in their frequency and distribution. In Asia, 36.5% of the K13 mutations were distributed within two areas--one in Cambodia, Vietnam, and Laos and the other in western Thailand, Myanmar, and China--with no overlap. In Africa, we observed a broad array of rare nonsynonymous mutations that were not associated with delayed parasite clearance. The gene-edited Dd2 transgenic line with the A578S mutation, which expresses the most frequently observed African allele, was found to be susceptible to artemisinin in vitro on a ring-stage survival assay.
CONCLUSIONS:
No evidence of artemisinin resistance was found outside Southeast Asia and China, where resistance-associated K13 mutations were confined. The common African A578S allele was not associated with clinical or in vitro resistance to artemisinin, and many African mutations appear to be neutral. (Funded by Institut Pasteur Paris and others.).
398 citations
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Medical Research Council1, Wellcome Trust Centre for Human Genetics2, Wellcome Trust Sanger Institute3, University of Oxford4, Malawi-Liverpool-Wellcome Trust Clinical Research Programme5, University of Buea6, Kwame Nkrumah University of Science and Technology7, Papua New Guinea Institute of Medical Research8, University of Ibadan9, National Institute for Biological Standards and Control10, University of Bamako11, University of London12, University College London13, Bernhard Nocht Institute for Tropical Medicine14, University of Colombo15, University of Khartoum16, Wellcome Trust17, University of Ghana18, National Institute for Medical Research19, Muhimbili University of Health and Allied Sciences20, Sapienza University of Rome21, University of Malawi22, University of Maryland, Baltimore23, Pasteur Institute24, Mahidol University25, Michigan State University26, Stockholm University27
TL;DR: These findings provide proof of principle that fine-resolution multipoint imputation, based on population-specific sequencing data, can substantially boost authentic GWA signals and enable fine mapping of causal variants in African populations.
Abstract: We report a genome-wide association (GWA) study of severe malaria in The Gambia. The initial GWA scan included 2,500 children genotyped on the Affymetrix 500K GeneChip, and a replication study included 3,400 children. We used this to examine the performance of GWA methods in Africa. We found considerable population stratification, and also that signals of association at known malaria resistance loci were greatly attenuated owing to weak linkage disequilibrium (LD). To investigate possible solutions to the problem of low LD, we focused on the HbS locus, sequencing this region of the genome in 62 Gambian individuals and then using these data to conduct multipoint imputation in the GWA samples. This increased the signal of association, from P = 4 × 10(-7) to P = 4 × 10(-14), with the peak of the signal located precisely at the HbS causal variant. Our findings provide proof of principle that fine-resolution multipoint imputation, based on population-specific sequencing data, can substantially boost authentic GWA signals and enable fine mapping of causal variants in African populations.
384 citations
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TL;DR: The findings support the view that, after appropriate training and with adequately packaged drugs made available, mothers can recognize and treat promptly and correctly malarial episodes in their children and, by doing so, reduce the incidence of severe disease.
Abstract: In rural, malaria-endemic Burkina Faso, we evaluated the impact of the use of pre-packaged antimalarial drugs (PPAM), by mothers in the home, on the progression of disease in children from uncomplicated fever to severe malaria. In each village of one province, a core group of opinion leaders (mainly older mothers) was trained in the management of uncomplicated malaria, including the administration of PPAM. Full courses of antimalarial (chloroquine) and antipyretic (aspirin) drugs were packaged in age-specific bags and made widely available through community health workers who were supplied through the existing drug distribution system. Drugs were sold under a cost-recovery scheme. Local schoolteachers conducted surveys in a random sample of 32 villages at the end of the high transmission seasons in 1998 and 1999. Disease history and the treatment received were investigated for all children under the age of 6 years having suffered from a fever episode in the previous 4 weeks. 'Uncomplicated malaria' was defined as every episode of fever and 'severe malaria' as every episode of fever followed by convulsions or loss of consciousness. During the study period, 56%[95% confidence interval (CI) 50-62%] of 3202 fever episodes in children under 6 years of age were treated promptly by mothers with the pre-packaged drugs made available by the study. A total of 59% of children receiving PPAM were reported to have received the drugs over the prescribed 3-day period, while 52% received the correct age-specific dose. PPAM use was similar among literate (61%) and non-literate mothers (55%) (P = 0.08). The overall reported risk of developing severe malaria was 8%. This risk was lower in children treated with PPAM (5%) than in children not treated with PPAM (11%) (risk ratio = 0.47; 95% CI 0.37, 0.60; P < 0.0001). This estimate of the impact of PPAM was largely unchanged when account was taken of potential confounding by age, sex, maternal literacy status, year or village. Our findings support the view that, after appropriate training and with adequately packaged drugs made available, mothers can recognize and treat promptly and correctly malarial episodes in their children and, by doing so, reduce the incidence of severe disease.
197 citations
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University of Oxford1, Royal Victoria Teaching Hospital2, University of London3, Medical Research Council4, University of Bamako5, Sapienza University of Rome6, University for Development Studies7, University of Ghana8, Kwame Nkrumah University of Science and Technology9, University of Ibadan10, University of Buea11, Wellcome Trust12, Imperial College London13, University of Melbourne14, University of Malawi15, University College London16, University of Western Australia17, Papua New Guinea Institute of Medical Research18, Swansea University19, Divine Word University20
TL;DR: The finding that G6PD deficiency has opposing effects on different fatal complications of P. falciparum infection indicates that the evolutionary origins of this common human genetic disorder are more complex than previously supposed.
Abstract: The Malaria Genomic Epidemiology Network reports a large multicenter association study for severe malaria due to Plasmodium falciparum in 11,890 cases and 17,441 controls from 12 locations in Africa, Asia and Oceania They examine 27 loci previously associated with severe malaria and replicate associations at the HBB, ABO, ATP2B4, G6PD and CD40LG loci, but they fail to replicate other previously reported associations
196 citations
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TL;DR: A randomized trial reported by Alassane Dicko and colleagues shows that intermittent preventive treatment for malaria in children who are protected from mosquitoes by insecticide-treated bednets provides substantial protection from malaria.
Abstract: Background: Previous studies have shown that in areas of seasonal malaria transmission, intermittent preventive treatment of malaria in children (IPTc), targeting the transmission season, reduces the incidence of clinical malaria. However, these studies were conducted in communities with low coverage with insecticide-treated nets (ITNs). Whether IPTc provides additional protection to children sleeping under an ITN has not been established. Methods and Findings: To assess whether IPTc provides additional protection to children sleeping under an ITN, we conducted a randomised, double-blind, placebo-controlled trial of IPTc with sulphadoxine pyrimethamine (SP) plus amodiaquine (AQ) in three localities in Kati, Mali. After screening, eligible children aged 3–59 mo were given a long-lasting insecticide-treated net (LLIN) and randomised to receive three rounds of active drugs or placebos. Treatments were administered under observation at monthly intervals during the high malaria transmission season in August, September, and October 2008. Adverse events were monitored immediately after the administration of each course of IPTc and throughout the follow-up period. The primary endpoint was clinical episodes of malaria recorded through passive surveillance by study clinicians available at all times during the follow-up. Cross-sectional surveys were conducted in 150 randomly selected children weekly and in all children at the end of the malaria transmission season to assess usage of ITNs and the impact of IPTc on the prevalence of malaria, anaemia, and malnutrition. Cox regression was used to compare incidence rates between intervention and control arms. The effects of IPTc on the prevalence of malaria infection and anaemia were estimated using logistic regression. 3,065 children were screened and 3,017 (1,508 in the control and 1,509 in the intervention arm) were enrolled in the study. 1,485 children (98.5%) in the control arm and 1,481 (98.1%) in the intervention arm completed follow-up. During the intervention period, the proportion of children reported to have slept under an ITN was 99.7% in the control and 99.3% in intervention arm (p=0.45). A total of 672 episodes of clinical malaria defined as fever or a history of fever and the presence of at least 5,000 asexual forms of Plasmodium falciparum per microlitre (incidence rate of 1.90; 95% confidence interval [CI] 1.76–2.05 episodes per person year) were observed in the control arm versus 126 (incidence rate of 0.34; 95% CI 0.29–0.41 episodes per person year) in the intervention arm, indicating a protective effect (PE) of 82% (95% CI 78%–85%) (p,0.001) on the primary endpoint. There were 15 episodes of severe malaria in children in the control arm compared to two in children in the intervention group giving a PE of 87% (95% CI 42%–99%) (p=0.001). IPTc reduced the prevalence of malaria infection by 85% (95% CI 73%–92%) (p,0.001) during the intervention period and by 46% (95% CI 31%–68%) (p,0.001) at the end of the intervention period. The prevalence of moderate anaemia (haemoglobin [Hb] ,8 g/dl) was reduced by 47% (95% CI 15%–67%) (p,0.007) at the end of intervention period. The frequencies of adverse events were similar between the two arms. There was no drug-related serious adverse event. Conclusions: IPTc given during the malaria transmission season provided substantial protection against clinical episodes of malaria, malaria infection, and anaemia in children using an LLIN. SP+AQ was safe and well tolerated. These findings indicate that IPTc could make a valuable contribution to malaria control in areas of seasonal malaria transmission alongside other interventions. Trial Registration: ClinicalTrials.gov NCT00738946 Please see later in the article for the Editors’ Summary.
152 citations
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01 Feb 2015
TL;DR: In this article, the authors describe the integrative analysis of 111 reference human epigenomes generated as part of the NIH Roadmap Epigenomics Consortium, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression.
Abstract: The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but epigenomic studies lack a similar reference. To address this need, the NIH Roadmap Epigenomics Consortium generated the largest collection so far of human epigenomes for primary cells and tissues. Here we describe the integrative analysis of 111 reference human epigenomes generated as part of the programme, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression. We establish global maps of regulatory elements, define regulatory modules of coordinated activity, and their likely activators and repressors. We show that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease. Our results demonstrate the central role of epigenomic information for understanding gene regulation, cellular differentiation and human disease.
4,409 citations
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Princeton University1, Public Health Foundation of India2, Center for Disease Dynamics, Economics & Policy3, University of the Witwatersrand4, Aga Khan University5, University of Oxford6, Food and Drug Administration7, Institute of Tropical Medicine Antwerp8, Aberdeen Royal Infirmary9, University of Antwerp10, National Veterinary Institute11, Duke University12, Karolinska Institutet13, St. John's University of Tanzania14, University of Cuenca15, Wellcome Trust16, St George's, University of London17, McMaster University18, Uppsala University19
TL;DR: The global situation of antibiotic resistance, its major causes and consequences, and key areas in which action is urgently needed are described and identified.
Abstract: The causes of antibiotic resistance are complex and include human behaviour at many levels of society; the consequences affect everybody in the world. Similarities with climate change are evident. Many efforts have been made to describe the many different facets of antibiotic resistance and the interventions needed to meet the challenge. However, coordinated action is largely absent, especially at the political level, both nationally and internationally. Antibiotics paved the way for unprecedented medical and societal developments, and are today indispensible in all health systems. Achievements in modern medicine, such as major surgery, organ transplantation, treatment of preterm babies, and cancer chemotherapy, which we today take for granted, would not be possible without access to effective treatment for bacterial infections. Within just a few years, we might be faced with dire setbacks, medically, socially, and economically, unless real and unprecedented global coordinated actions are immediately taken. Here, we describe the global situation of antibiotic resistance, its major causes and consequences, and identify key areas in which action is urgently needed.
3,181 citations
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TL;DR: All three fast turnaround sequencers evaluated here were able to generate usable sequence, however there are key differences between the quality of that data and the applications it will support.
Abstract: Next generation sequencing (NGS) technology has revolutionized genomic and genetic research. The pace of change in this area is rapid with three major new sequencing platforms having been released in 2011: Ion Torrent’s PGM, Pacific Biosciences’ RS and the Illumina MiSeq. Here we compare the results obtained with those platforms to the performance of the Illumina HiSeq, the current market leader. In order to compare these platforms, and get sufficient coverage depth to allow meaningful analysis, we have sequenced a set of 4 microbial genomes with mean GC content ranging from 19.3 to 67.7%. Together, these represent a comprehensive range of genome content. Here we report our analysis of that sequence data in terms of coverage distribution, bias, GC distribution, variant detection and accuracy. Sequence generated by Ion Torrent, MiSeq and Pacific Biosciences technologies displays near perfect coverage behaviour on GC-rich, neutral and moderately AT-rich genomes, but a profound bias was observed upon sequencing the extremely AT-rich genome of Plasmodium falciparum on the PGM, resulting in no coverage for approximately 30% of the genome. We analysed the ability to call variants from each platform and found that we could call slightly more variants from Ion Torrent data compared to MiSeq data, but at the expense of a higher false positive rate. Variant calling from Pacific Biosciences data was possible but higher coverage depth was required. Context specific errors were observed in both PGM and MiSeq data, but not in that from the Pacific Biosciences platform. All three fast turnaround sequencers evaluated here were able to generate usable sequence. However there are key differences between the quality of that data and the applications it will support.
1,967 citations
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TL;DR: The design of genomewide association studies is described and the extent to which the data they provide are useful in predicting the risk of disease is considered.
Abstract: Over the past 5 years, genomewide association studies have yielded a wealth of insight into genes and chromosomal loci that contribute to susceptibility to disease. This article, the second in the Genomic Medicine series, describes the design of these studies and considers the extent to which the data they provide are useful in predicting the risk of disease.
1,500 citations