Dr Ipsita Sinha

Research Area: Global Health
Technology Exchange: Bioinformatics, Computational biology, Medical statistics, SNP typing and Statistical genetics
Scientific Themes: Tropical Medicine & Global Health and Clinical Trials & Epidemiology
Keywords: Malaria, Epidemiology, modelling, pathogenesis, GIS, Artemisinin, Elimination and Clinical Trials
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Dr Ipsita Sinha is part of the Epidemiology department at MORU, and a Research Physician in Tropical Medicine at the University of Oxford. She is also an honorary medical registrar at the John Radcliffe Hospital in Oxford. Ipsita’s research interests include spatiotemporal modelling, GIS mapping, population movement with dynamic modelling of malaria spread, parasite genetics and evolution, with emphasis on artemisinin resistance and malaria elimination. She particularly enjoys travelling to different field sites and gaining practical experience in the pathogenesis of malaria and challenges in monitoring and managing the disease at a local and national level.

Ipsita is currently pursuing her doctoral studies at University of Oxford in mapping and predicting the potential spread of malaria and artemisinin resistance in South-East Asia and South Asia to better inform targeting of malaria control and elimination interventions. 

There are no collaborations listed for this principal investigator.

MalariaGEN Plasmodium falciparum Community Project. 2016. Genomic epidemiology of artemisinin resistant malaria. Elife, 5 (MARCH2016), | Show Abstract | Read more

The current epidemic of artemisinin resistant Plasmodium falciparum in Southeast Asia is the result of a soft selective sweep involving at least 20 independent kelch13 mutations. In a large global survey, we find that kelch13 mutations which cause resistance in Southeast Asia are present at low frequency in Africa. We show that African kelch13 mutations have originated locally, and that kelch13 shows a normal variation pattern relative to other genes in Africa, whereas in Southeast Asia there is a great excess of non-synonymous mutations, many of which cause radical amino-acid changes. Thus, kelch13 is not currently undergoing strong selection in Africa, despite a deep reservoir of variations that could potentially allow resistance to emerge rapidly. The practical implications are that public health surveillance for artemisinin resistance should not rely on kelch13 data alone, and interventions to prevent resistance must account for local evolutionary conditions, shown by genomic epidemiology to differ greatly between geographical regions.

Sinha I, Ekapirat N, Dondorp AM, Woodrow CJ. 2015. Use of a rapid test to assess plasma Plasmodium falciparum HRP2 and guide management of severe febrile illness. Malar J, 14 (1), pp. 362. | Show Abstract | Read more

BACKGROUND: Plasma Plasmodium falciparum histidine-rich protein-2 (PfHRP2) is the most accurate biomarker for severe malaria, but its measurement by ELISA has been considered too unwieldy to incorporate into clinical management. METHODS: Plasma samples covering a wide range of PfHRP2 concentrations were applied to rapid diagnostic tests (RDTs). RDTs were read by eye and digital capture, and PfHRP2 concentrations were measured via serial dilution with results compared to ELISA readings. RESULTS: The Paracheck (®) brand showed the strongest correlation (r(2) = 0.963) as well as the lowest inter-observer variability (combined kappa across band intensities for three observers = 0.938). Plasma PfHRP2 measurement via serial dilution showed minimal bias compared to ELISA and acceptable limits of agreement. Three different dilutions of a well characterized set of admission samples from uncomplicated and severe malaria patients studied in a low transmission setting gave an area under the receiver operator characteristic curve of 0.844 in terms of identifying severe malaria. CONCLUSIONS: These studies show that plasma PfHRP2 can be assessed via a single RDT, with application of a plasma dilution of 1:5 or 1:10 providing useful diagnostic information to assist in patient management or clinical trial inclusion.

Cited:

21

Scopus

Magrabi F, Baker M, Sinha I, Ong MS, Harrison S, Kidd MR, Runciman WB, Coiera E. 2015. Clinical safety of england's national programme for IT: A retrospective analysis of all reported safety events 2005 to 2011 International Journal of Medical Informatics, 84 (3), pp. 198-206. | Show Abstract | Read more

© 2015 Elsevier Ireland Ltd. Objective: To analyse patient safety events associated with England's national programme for IT (NPfIT). MethodsRetrospective analysis of all safety events managed by a dedicated IT safety team between September 2005 and November 2011 was undertaken. Events were reviewed against an existing classification for problems associated with IT. The proportion of reported events per problem type, consequences, source of report, resolution within 24. h, time of day and day of week were examined. Sub-group analyses were undertaken for events involving patient harm and those that occurred on a large scale. ResultsOf the 850 events analysed, 68% (n=574) described potentially hazardous circumstances, 24% (n=205) had an observable impact on care delivery, 4% (n=36) were a near miss, and 3% (n=22) were associated with patient harm, including three deaths (0.35%). Eleven events did not have a noticeable consequence (1%) and two were complaints ( < 1%). Amongst the events 1606 separate contributing problems were identified. Of these 92% were predominately associated with technical rather than human factors. Problems involving human factors were four times as likely to result in patient harm than technical problems (25% versus 8%; OR 3.98, 95%CI 1.90-8.34). Large-scale events affecting 10 or more individuals or multiple IT systems accounted for 23% (n=191) of the sample and were significantly more likely to result in a near miss (6% versus 4%) or impact the delivery of care (39% versus 20%; p < . 0.001). ConclusionEvents associated with NPfIT reinforce that the use of IT does create hazardous circumstances and can lead to patient harm or death. Large-scale patient safety events have the potential to affect many patients and clinicians, and this suggests that addressing them should be a priority for all major IT implementations.

Magrabi F, Baker M, Sinha I, Ong M-S, Harrison S, Kidd MR, Runciman WB, Coiera E. 2015. Clinical safety of England's national programme for IT: a retrospective analysis of all reported safety events 2005 to 2011. Int J Med Inform, 84 (3), pp. 198-206. | Show Abstract | Read more

OBJECTIVE: To analyse patient safety events associated with England's national programme for IT (NPfIT). METHODS: Retrospective analysis of all safety events managed by a dedicated IT safety team between September 2005 and November 2011 was undertaken. Events were reviewed against an existing classification for problems associated with IT. The proportion of reported events per problem type, consequences, source of report, resolution within 24h, time of day and day of week were examined. Sub-group analyses were undertaken for events involving patient harm and those that occurred on a large scale. RESULTS: Of the 850 events analysed, 68% (n=574) described potentially hazardous circumstances, 24% (n=205) had an observable impact on care delivery, 4% (n=36) were a near miss, and 3% (n=22) were associated with patient harm, including three deaths (0·35%). Eleven events did not have a noticeable consequence (1%) and two were complaints (<1%). Amongst the events 1606 separate contributing problems were identified. Of these 92% were predominately associated with technical rather than human factors. Problems involving human factors were four times as likely to result in patient harm than technical problems (25% versus 8%; OR 3·98, 95%CI 1·90-8.34). Large-scale events affecting 10 or more individuals or multiple IT systems accounted for 23% (n=191) of the sample and were significantly more likely to result in a near miss (6% versus 4%) or impact the delivery of care (39% versus 20%; p<0·001). CONCLUSION: Events associated with NPfIT reinforce that the use of IT does create hazardous circumstances and can lead to patient harm or death. Large-scale patient safety events have the potential to affect many patients and clinicians, and this suggests that addressing them should be a priority for all major IT implementations.

Gardner KB, Sinha I, Bustamante LY, Day NPJ, White NJ, Woodrow CJ. 2011. Protein-based signatures of functional evolution in Plasmodium falciparum BMC Evolutionary Biology, 11 (1), | Show Abstract | Read more

Abstract. Background: It has been known for over a decade that Plasmodium falciparum proteins are enriched in non-globular domains of unknown function. The potential for these regions of protein sequence to undergo high levels of genetic drift provides a fundamental challenge to attempts to identify the molecular basis of adaptive change in malaria parasites. Results: Evolutionary comparisons were undertaken using a set of forty P. falciparum metabolic enzyme genes, both within the hominid malaria clade (P. reichenowi) and across the genus (P. chabaudi). All genes contained coding elements highly conserved across the genus, but there were also a large number of regions of weakly or non-aligning coding sequence. These displayed remarkable levels of non-synonymous fixed differences within the hominid malaria clade indicating near complete release from purifying selection (dN/dS ratio at residues non-aligning across genus: 0.64, dN/dS ratio at residues identical across genus: 0.03). Regions of low conservation also possessed high levels of hydrophilicity, a marker of non-globularity. The propensity for such regions to act as potent sources of non-synonymous genetic drift within extant P. falciparum isolates was confirmed at chromosomal regions containing genes known to mediate drug resistance in field isolates, where 150 of 153 amino acid variants were located in poorly conserved regions. In contrast, all 22 amino acid variants associated with drug resistance were restricted to highly conserved regions. Additional mutations associated with laboratory-selected drug resistance, such as those in PfATPase4 selected by spiroindolone, were similarly restricted while mutations in another calcium ATPase (PfSERCA, a gene proposed to mediate artemisinin resistance) that reach significant frequencies in field isolates were located exclusively in poorly conserved regions consistent with genetic drift. Conclusion: Coding sequences of malaria parasites contain prospectively definable domains subject to neutral or nearly neutral evolution on a scale that appears unrivalled in biology. This distinct evolutionary landscape has potential to confound analytical methods developed for other genera. Against this tide of genetic drift, polymorphisms mediating functional change stand out to such an extent that evolutionary context provides a useful signal for identifying the molecular basis of drug resistance in malaria parasites, a finding that is of relevance to both genome-wide and candidate gene studies in this genus. © 2011 Gardner et al; licensee BioMed Central Ltd.

Gardner KB, Sinha I, Bustamante LY, Day NP, White NJ, Woodrow CJ. 2011. Protein-based signatures of functional evolution in Plasmodium falciparum. BMC Evol Biol, 11 (1), pp. 257. | Show Abstract | Read more

BACKGROUND: It has been known for over a decade that Plasmodium falciparum proteins are enriched in non-globular domains of unknown function. The potential for these regions of protein sequence to undergo high levels of genetic drift provides a fundamental challenge to attempts to identify the molecular basis of adaptive change in malaria parasites. RESULTS: Evolutionary comparisons were undertaken using a set of forty P. falciparum metabolic enzyme genes, both within the hominid malaria clade (P. reichenowi) and across the genus (P. chabaudi). All genes contained coding elements highly conserved across the genus, but there were also a large number of regions of weakly or non-aligning coding sequence. These displayed remarkable levels of non-synonymous fixed differences within the hominid malaria clade indicating near complete release from purifying selection (dN/dS ratio at residues non-aligning across genus: 0.64, dN/dS ratio at residues identical across genus: 0.03). Regions of low conservation also possessed high levels of hydrophilicity, a marker of non-globularity. The propensity for such regions to act as potent sources of non-synonymous genetic drift within extant P. falciparum isolates was confirmed at chromosomal regions containing genes known to mediate drug resistance in field isolates, where 150 of 153 amino acid variants were located in poorly conserved regions. In contrast, all 22 amino acid variants associated with drug resistance were restricted to highly conserved regions. Additional mutations associated with laboratory-selected drug resistance, such as those in PfATPase4 selected by spiroindolone, were similarly restricted while mutations in another calcium ATPase (PfSERCA, a gene proposed to mediate artemisinin resistance) that reach significant frequencies in field isolates were located exclusively in poorly conserved regions consistent with genetic drift. CONCLUSION: Coding sequences of malaria parasites contain prospectively definable domains subject to neutral or nearly neutral evolution on a scale that appears unrivalled in biology. This distinct evolutionary landscape has potential to confound analytical methods developed for other genera. Against this tide of genetic drift, polymorphisms mediating functional change stand out to such an extent that evolutionary context provides a useful signal for identifying the molecular basis of drug resistance in malaria parasites, a finding that is of relevance to both genome-wide and candidate gene studies in this genus.

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