Summary Background Artemisinin-resistant falciparum malaria has arisen in western Cambodia. A concerted international effort is underway to contain artemisinin-resistant Plasmodium falciparum , but ...containment strategies are dependent on whether resistance has emerged elsewhere. We aimed to establish whether artemisinin resistance has spread or emerged on the Thailand–Myanmar (Burma) border. Methods In malaria clinics located along the northwestern border of Thailand, we measured six hourly parasite counts in patients with uncomplicated hyperparasitaemic falciparum malaria (≥4% infected red blood cells) who had been given various oral artesunate-containing regimens since 2001. Parasite clearance half-lives were estimated and parasites were genotyped for 93 single nucleotide polymorphisms. Findings 3202 patients were studied between 2001 and 2010. Parasite clearance half-lives lengthened from a geometric mean of 2·6 h (95% CI 2·5–2·7) in 2001, to 3·7 h (3·6–3·8) in 2010, compared with a mean of 5·5 h (5·2–5·9) in 119 patients in western Cambodia measured between 2007 and 2010. The proportion of slow-clearing infections (half-life ≥6·2 h) increased from 0·6% in 2001, to 20% in 2010, compared with 42% in western Cambodia between 2007 and 2010. Of 1583 infections genotyped, 148 multilocus parasite genotypes were identified, each of which infected between two and 13 patients. The proportion of variation in parasite clearance attributable to parasite genetics increased from 30% between 2001 and 2004, to 66% between 2007 and 2010. Interpretation Genetically determined artemisinin resistance in P falciparum emerged along the Thailand–Myanmar border at least 8 years ago and has since increased substantially. At this rate of increase, resistance will reach rates reported in western Cambodia in 2–6 years. Funding The Wellcome Trust and National Institutes of Health.
Summary Background Emergence of artemisinin resistance in southeast Asia poses a serious threat to the global control of Plasmodium falciparum malaria. Discovery of the K13 marker has transformed ...approaches to the monitoring of artemisinin resistance, allowing introduction of molecular surveillance in remote areas through analysis of DNA. We aimed to assess the spread of artemisinin-resistant P falciparum in Myanmar by determining the relative prevalence of P falciparum parasites carrying K13-propeller mutations. Methods We did this cross-sectional survey at malaria treatment centres at 55 sites in ten administrative regions in Myanmar, and in relevant border regions in Thailand and Bangladesh, between January, 2013, and September, 2014. K13 sequences from P falciparum infections were obtained mainly by passive case detection. We entered data into two geostatistical models to produce predictive maps of the estimated prevalence of mutations of the K13 propeller region across Myanmar. Findings Overall, 371 (39%) of 940 samples carried a K13-propeller mutation. We recorded 26 different mutations, including nine mutations not described previously in southeast Asia. In seven (70%) of the ten administrative regions of Myanmar, the combined K13-mutation prevalence was more than 20%. Geospatial mapping showed that the overall prevalence of K13 mutations exceeded 10% in much of the east and north of the country. In Homalin, Sagaing Region, 25 km from the Indian border, 21 (47%) of 45 parasite samples carried K13-propeller mutations. Interpretation Artemisinin resistance extends across much of Myanmar. We recorded P falciparum parasites carrying K13-propeller mutations at high prevalence next to the northwestern border with India. Appropriate therapeutic regimens should be tested urgently and implemented comprehensively if spread of artemisinin resistance to other regions is to be avoided. Funding Wellcome Trust–Mahidol University–Oxford Tropical Medicine Research Programme and the Bill & Melinda Gates Foundation.
Background and Aims: To compare the performance characteristics of C-MAC video, McCoy, and Macintosh laryngoscopes in elective cervical spine surgery. The primary objective was to assess the ease of ...intubation with the three study devices. The secondary objectives were the time to intubation and hemodynamic responses during intubation.
Material and Methods : The prospective observational comparative study was conducted in a tertiary care hospital. Adult ASA 1 and 11 patients who underwent elective cervical spine surgery were included in the study. Patients with unstable spine and trauma were excluded. The analysis of variance, Bonferroni test, Chi square test and multiple comparison tests were used to compare the performance characteristics of laryngoscopes.
Results: The C-MAC video laryngoscope improved glottis view by improving the modified Cormack-Lehane (CL) score and the percentage of glottis opening (POGO) score compared to McCoy and Macintosh laryngoscopes. The ease of intubation was better with the C-MAC video laryngoscope compared to the McCoy and Macintosh laryngoscopes. The time to intubation was comparable between the three laryngoscopes. The C-MAC video and McCoy laryngoscopes had 100% successful first attempt intubations while it was 90% for the Macintosh laryngoscope. Hemodynamic variables observed during intubation were comparable between the three groups.
Conclusion: The use of C-MAC video laryngoscope resulted in better visualization of the glottis and easier tracheal intubation as compared to the Macintosh and McCoy laryngoscopes in cervical spine surgery. Both C-MAC video and McCoy laryngoscopes had 100% successful first attempt intubation.
Artemisinin-based combination therapies are the first line of treatment for Plasmodium falciparum infections worldwide, but artemisinin resistance has risen rapidly in Southeast Asia over the past ...decade. Mutations in the kelch13 gene have been implicated in this resistance. We used longitudinal genomic surveillance to detect signals in kelch13 and other loci that contribute to artemisinin or partner drug resistance. We retrospectively sequenced the genomes of 194 P. falciparum isolates from five sites in Northwest Thailand, over the period of a rapid increase in the emergence of artemisinin resistance (2001-2014).
We evaluate statistical metrics for temporal change in the frequency of individual SNPs, assuming that SNPs associated with resistance increase in frequency over this period. After Kelch13-C580Y, the strongest temporal change is seen at a SNP in phosphatidylinositol 4-kinase, which is involved in a pathway recently implicated in artemisinin resistance. Furthermore, other loci exhibit strong temporal signatures which warrant further investigation for involvement in artemisinin resistance evolution. Through genome-wide association analysis we identify a variant in a kelch domain-containing gene on chromosome 10 that may epistatically modulate artemisinin resistance.
This analysis demonstrates the potential of a longitudinal genomic surveillance approach to detect resistance-associated gene loci to improve our mechanistic understanding of how resistance develops. Evidence for additional genomic regions outside of the kelch13 locus associated with artemisinin-resistant parasites may yield new molecular markers for resistance surveillance, which may be useful in efforts to reduce the emergence or spread of artemisinin resistance in African parasite populations.
Evolving resistance to arte misi ni n-based compounds threatens to derail attempts to control malaria. Resistance has been confirmed in western Cambodia and has recently emerged in western Thailand, ...but is absent from neighboring Laos. Artemisinin resistance results in reduced parasite clearance rates (CRs) after treatment. We used a two-phase strategy to identify genome region(s) underlying this ongoing selective event. Geographical differentiation and haplotype structure at 6969 polymorphic single-nucleotide polymorphisms (SNPs) in 91 parasites from Cambodia, Thailand, and Laos identified 33 genome regions under strong selection. We screened SNPs and microsatellites within these regions in 715 parasites from Thailand, identifying a selective sweep on chromosome 13 that shows strong association (P = 10⁻⁶ to 10⁻¹²) with slow CRs, illustrating the efficacy of targeted association for identifying the genetic basis of adaptive traits.
Both population-level epidemiological data and individual-level biological data are needed to control the coronavirus disease 2019 (COVID-19) pandemic. Population-level data are widely available and ...efforts to combat COVID-19 have generated proliferate data on the biology and immunoresponse to the causative pathogen, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, there remains a paucity of systemized data on this subject.
In this review, we attempt to extract systemized data on the biology and immuno-response to SARS-CoV-2 from the most up-to-date peer-reviewed studies. We will focus on the biology of the virus and immunological variations that are key for determining long-term immunity, transmission potential, and prognosis.
Peer-reviewed articles were sourced from the PubMed database and by snowballing search of selected publications. Search terms included: “Novel Coronavirus” OR “COVID-19” OR “SARS-CoV-2” OR “2019-nCoV” AND “Immunity” OR “Immune Response” OR “Antibody Response” OR “Immunologic Response”. Studies published from December 31, 2019 to December 31, 2020 were included. To ensure validity, papers in pre-print were excluded.
Of 2 889 identified papers, 36 were included. Evidence from these studies suggests early seroconversion in patients infected with SARS-CoV-2. Antibody titers appear to markedly increase two weeks after infection, followed by a plateau. A more robust immune response is seen in patients with severe COVID-19 as opposed to mild or asymptomatic presentations. This trend persists with regard to the length of antibody maintenance. However, overall immunity appears to wane within two to three months post-infection.
Findings of this study indicate that immune responses to SARS-CoV-2 follow the general pattern of viral infection. Immunity generated through natural infection appears to be short, suggesting a need for long-term efforts to control the pandemic. Antibody testing will be essential to gauge the epidemic and inform decision-making on effective strategies for treatment and prevention. Further research is needed to illustrate immunoglobulin-specific roles and neutralizing antibody activity.
Abstract
Background
Non-contrast Computerised Tomography (NCCT) of brain is the gold standard investigation for diagnosis and management of Traumatic brain injury (TBI). Asymmetrical CT brain images ...as a result of improper head positioning in the CT gantry will compromise the diagnostic value. Therefore, this audit aimed to assess the degree of asymmetry in CT brain studies carried out in TBI patients.
Methods
This audit was carried out at a level one trauma centre and included CT scans of TBI patients with a Glasgow come scale (GCS) score ≤ 13, admitted to the Neurological intensive care unit (NICU). The first cycle involved a period of three months. The data collected included demographic data and variables such as GCS at the time of the scan and whether the patient was intubated or not. The visualisation of bilateral internal auditory meatuses was used as landmark to determine scan symmetry. If the internal auditory meatus on both sides were visible on the same slice of CT scan, it was considered symmetric. The degree of asymmetry was gauged based on the axial slice difference between bilateral meatuses. The data collected was tabulated and presented to Neurosurgery residents and a checklist was formulated which had to be followed while positioning the patient on CT table prior to imaging.
Results
The first cycle of the audit showed that 83.8% of scans were asymmetric and among them 44.1% revealed gross asymmetry affecting interpretation of the scan. Following, implementation of the checklist the percentage of gross asymmetry dropped to 21.86% in the second and to 22.22% in the third audit.
Conclusion
The use of checklist prior to CT brain studies showed sustainable improvement in reducing gross asymmetry and in acquisition of symmetrical CT brain images.
Multiple kelch13 alleles conferring artemisinin resistance (ART-R) are currently spreading through Southeast Asian malaria parasite populations, providing a unique opportunity to observe an ongoing ...soft selective sweep, investigate why resistance alleles have evolved multiple times and determine fundamental population genetic parameters for Plasmodium We sequenced kelch13 (n = 1,876), genotyped 75 flanking SNPs, and measured clearance rate (n = 3,552) in parasite infections from Western Thailand (2001-2014). We describe 32 independent coding mutations including common mutations outside the kelch13 propeller associated with significant reductions in clearance rate. Mutations were first observed in 2003 and rose to 90% by 2014, consistent with a selection coefficient of ∼0.079. ART-R allele diversity rose until 2012 and then dropped as one allele (C580Y) spread to high frequency. The frequency with which adaptive alleles arise is determined by the rate of mutation and the population size. Two factors drive this soft sweep: (1) multiple kelch13 amino-acid mutations confer resistance providing a large mutational target-we estimate the target is 87-163 bp. (2) The population mutation parameter (Θ = 2N
μ) can be estimated from the frequency distribution of ART-R alleles and is ∼5.69, suggesting that short term effective population size is 88 thousand to 1.2 million. This is 52-705 times greater than N
estimated from fluctuation in allele frequencies, suggesting that we have previously underestimated the capacity for adaptive evolution in Plasmodium Our central conclusions are that retrospective studies may underestimate the complexity of selective events and the N
relevant for adaptation for malaria is considerably higher than previously estimated.
A recent study by Ooi and Ooi (EH Ooi, ET Ooi, Mass transport in biological tissues: Comparisons between single- and dual-porosity models in the context of saline-infused radiofrequency ablation, ...Applied Mathematical Modelling, 2017, 41, 271-284) has shown that single-porosity (SP) models for describing fluid transport in biological tissues significantly underestimate the fluid penetration depth when compared to dual-porosity (DP) models. This has raised some concerns on whether the SP model, when coupled with models of radiofrequency ablation (RFA) to simulate saline-infused RFA, could lead to an underestimation of the coagulation size. This paper compares the coagulation volumes obtained following saline-infused RFA predicted based on the SP and DP models for fluid transport. Results showed that the SP model predicted coagulation zones that are consistently 0.5 to 0.9 times smaller than that of DP model. This may be explained by the low permeability value of the tissue interstitial space, which causes the majority of the saline to flow through the vasculature. The absence of fluid flow tracking in the vasculature in the SP model meant that any flow of saline into the vasculature is treated as losses and do not contribute to the saline penetration depth of the tissue. Comparisons with experimental results from the literature revealed that the DP models predicted coagulation zone sizes that are closer to the experimental values than the SP models. This supports the hypothesis that the SP model is a poor choice for simulating the outcome of saline-infused RFA.
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