ORCID Profile
0000-0002-4520-2701
Current Organisations
University of Queensland
,
Lee Kong Chian School of Medicine
,
University of Melbourne
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Publisher: Springer Science and Business Media LLC
Date: 26-05-2015
Publisher: Public Library of Science (PLoS)
Date: 29-03-2022
Publisher: Public Library of Science (PLoS)
Date: 13-10-2022
DOI: 10.1371/JOURNAL.PNTD.0010864
Abstract: Dengue can be complicated by severe outcomes including cardiac impairment, and the lack of reliable prognostic biomarkers poses a challenge in managing febrile dengue patients. Here, we investigated the functionality of soluble suppressor of tumorigenicity (sST2) as a predictive marker of severe dengue and its association in dengue-associated cardiac impairment. Plasma s les, aged years, collected from 36 dengue fever, 43 dengue with warning signs, 11 severe dengue (collected at febrile, critical and recovery phases) and 30 controls were assayed for plasma levels of sST2, troponin T and N-terminal (NT)-pro hormone brain natriuretic peptide (NT-proBNP) by ELISA. Cardiac parameters: stroke index (SI), cardiac index (CI) and Granov-Goor Index (GGI) were measured with a bioimpedance device during the different phases for dengue subjects and once for the controls. In the febrile, critical and early recovery phases, sST2 levels were significantly elevated in dengue participants and sST2 levels increased with increasing disease severity (P 0.01 for all). sST2 concentrations were negatively correlated with SI (r = -0.48 P 0.001, r = -0.55 P 0.001), CI (r = -0.26 P = 0.02, r = -0.6: P 0.001) and GGI (r = -0.44 P 0.001, r = -0.57 P 0.001) in the critical and early recovery phases. In contrast, sST2 levels in the febrile and critical phases, were positive correlated to troponin T (r = 0.44, P 0.001 r = 0.22, P = 0.03, respectively) and NT-proBNP (r = 0.21, P = 0.03 r = 0.35, P 0.001). ROC analysis demonstrated sST2 as a good biomarker of severe dengue in the critical phase, AUROC 0.79, P 0.001. sST2 levels were elevated in patients with dengue especially in cases of severe dengue. Furthermore, increased sST2 levels were associated with cardiac indicators suggesting lower cardiac performance. While further research is needed to demonstrate its clinical utility, sST2 may be a useful prognostic biomarker of severe dengue.
Publisher: Public Library of Science (PLoS)
Date: 30-03-2023
Publisher: Elsevier BV
Date: 11-2016
Abstract: Numerous efforts to understand the functional roles of antibodies demonstrated that they can protect against malaria. However, it is unclear which antibody responses are the best correlates of immunity, and which antibody functions are most important in protection from disease. Understanding the role of antibodies in protection against malaria is crucial for antimalarial vaccine design. In this review, the specific functional properties of naturally acquired and vaccine-induced antibodies that correlate to protection from the blood stages of Plasmodium falciparum malaria are re-examined and the gaps in knowledge related to antibody function in malarial immunity are highlighted.
Publisher: Springer New York
Date: 2015
DOI: 10.1007/978-1-4939-2815-6_12
Abstract: Infection with Plasmodium falciparum parasites causes the majority of malaria-related morbidity and mortality. Constant exposure to the pathogen leads to the acquisition of antibodies and high levels of antibodies have been associated with clinical protection against malaria. A possible protective mechanism is the opsonization of parasites, or malaria-infected erythrocytes (IEs), for phagocytic clearance. Current assays use adherent or chemically differentiated THP-1 cells to evaluate opsonic antibodies in patients' s les, but these assays are often time consuming and damage the effector cells. We have developed a high throughput flow cytometry-based phagocytosis assay using undifferentiated THP-1 cells to quantify the opsonic activity against late stage P. falciparum-IEs. Opsonic antibodies bound to IEs promote their phagocytic uptake through Fcγ receptors found on THP-1 cells. Moreover, undifferentiated THP-1 cells do not express CD36, a surface scavenger receptor that promotes non-opsonic phagocytosis. This technical advance allows quantification of opsonic antibodies and is an important tool for the performance of large, population-based studies of malaria immunity, and to provide a significant increase in the statistical power for such studies.
Publisher: Oxford University Press (OUP)
Date: 12-10-2023
DOI: 10.1093/CID/CIAD637
Publisher: Public Library of Science (PLoS)
Date: 09-12-2021
Publisher: Springer Science and Business Media LLC
Date: 27-05-2019
DOI: 10.1038/S41598-019-44340-X
Abstract: In a randomised trial comparing intermittent screening and treatment (IST) with dihydroartemisinin-piperaquine (DP) and intermittent preventive therapy against malaria in pregnancy (IPT) with sulfadoxine-pyrimethamine (SP) in Malawi, the impacts of IST-DP and IPT-SP on the development and maintenance of malaria antibody immunity were compared. Pregnant Malawian women were randomised to receive IST-DP or IPT-SP. In a nested study, paired enrolment and delivery plasma s les from 681 women were assayed for antibodies against recombinant antigens and for IgG and opsonising antibodies to antigens found on infected erythrocytes (IEs). At delivery, antibody responses did not differ between study arms. Between enrolment and delivery, antibodies to recombinant antigens decreased, whereas antibodies to IEs including opsonising antibodies remained stable. Overall, changes in antibody responses over pregnancy did not differ by treatment arm. Stratifying by gravidity, antibody to schizont extract decreased more in multigravidae receiving IST-DP than IPT-SP. There was minimal impact of treatment arm on the development and maintenance of malaria immunity. While antibodies to recombinant antigens declined between enrolment and delivery, antibodies directed against IEs tended to be more stable, suggesting longer-lasting protection. Clinical trial registration: Pa n African Clinical Trials Registry (PACTR201103000280319) 14/03/2011. URL: www.isrctn.com/ISRCTN69800930 .
Publisher: Oxford University Press (OUP)
Date: 05-05-2014
Abstract: As malaria control is intensified, pregnant women may be less exposed to malaria, thus affecting the acquisition of protective antibody. Plasma s les were collected from Malawian and Papua New Guinean (PNG) pregnant women enrolled over 7-year periods, during which malaria prevalence fell by over two thirds. Immunoglobulin G (IgG) levels to schizont extract, merozoite antigens, and VAR2CSA-DBL5ε were measured by enzyme-linked immunosorbent assay (ELISA). Levels of IgG to variant surface antigens of infected erythrocytes (IEs) and merozoites and levels of opsonizing IgG to IEs were measured by flow cytometry. In both settings, levels of antibodies in pregnant women to recombinant antigens and to intact IEs but not of opsonizing antibodies decreased over time. After adjustment for coverage with insecticide-treated bed nets (ITNs), these differences disappeared in the Malawian cohort, whereas in the PNG cohort, time was independently associated with a decrease in several antibody responses measured by ELISA. The impact of falling parasite prevalence on anti-Plasmodium falciparum serological indicators in pregnant women varies by setting. Increased ITN coverage may affect development of antibodies to recombinant antigens, but levels of opsonizing IgG remained stable over time. Opsonizing IgG against placental-binding IEs may persist, thus offering longer-lasting protection against malaria during pregnancy.
Publisher: American Society for Microbiology
Date: 29-06-2021
DOI: 10.1128/MSYSTEMS.00347-21
Abstract: Plasmodium infection causes devastating disease and high mortality in young children. Immunity develops progressively as children acquire protection against severe disease, although reinfections and recrudescences still occur throughout life in areas of endemicity, partly due to parasite immunoevasion via switching of variant proteins such as Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) expressed on the infected erythrocyte surface.
Publisher: JMIR Publications Inc.
Date: 13-04-2022
DOI: 10.2196/29594
Abstract: Extended reality, which encompasses virtual reality (VR), augmented reality (AR), and mixed reality (MR), is increasingly used in medical education. Studies assessing the effectiveness of these new educational modalities should measure relevant outcomes using outcome measurement tools with validity evidence. Our aim is to determine the choice of outcomes, measurement instruments, and the use of measurement instruments with validity evidence in randomized controlled trials (RCTs) on the effectiveness of VR, AR, and MR in medical student education. We conducted a systematic mapping review. We searched 7 major bibliographic databases from January 1990 to April 2020, and 2 reviewers screened the citations and extracted data independently from the included studies. We report our findings in line with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Of the 126 retrieved RCTs, 115 (91.3%) were on VR and 11 (8.7%) were on AR. No RCT on MR in medical student education was found. Of the 115 studies on VR, 64 (55.6%) were on VR simulators, 30 (26.1%) on screen-based VR, 9 (7.8%) on VR patient simulations, and 12 (10.4%) on VR serious games. Most studies reported only a single outcome and immediate postintervention assessment data. Skills outcome was the most common outcome reported in studies on VR simulators (97%), VR patient simulations (100%), and AR (73%). Knowledge was the most common outcome reported in studies on screen-based VR (80%) and VR serious games (58%). Less common outcomes included participants’ attitudes, satisfaction, cognitive or mental load, learning efficacy, engagement or self-efficacy beliefs, emotional state, competency developed, and patient outcomes. At least one form of validity evidence was found in approximately half of the studies on VR simulators (55%), VR patient simulations (56%), VR serious games (58%), and AR (55%) and in a quarter of the studies on screen-based VR (27%). Most studies used assessment methods that were implemented in a nondigital format, such as paper-based written exercises or in-person assessments where examiners observed performance (72%). RCTs on VR and AR in medical education report a restricted range of outcomes, mostly skills and knowledge. The studies largely report immediate postintervention outcome data and use assessment methods that are in a nondigital format. Future RCTs should include a broader set of outcomes, report on the validity evidence of the measurement instruments used, and explore the use of assessments that are implemented digitally.
Publisher: Springer New York
Date: 2015
DOI: 10.1007/978-1-4939-2815-6_17
Abstract: Constant exposure to Plasmodium falciparum leads to acquisition of malarial antibodies that can protect against the clinical consequences of infection. One important target of such antibodies is against the parasite-infected erythrocyte (IEs). Current established assays to test the efficacy of antibodies in preventing parasite growth include direct parasite growth inhibition, the agglutination of IEs, and the inhibition of adhesion of IEs (to quantify antibody that inhibits adhesion to purified receptors or cells).However, many of these assays are labor-intensive and low-output which limits study sizes to small cohorts. Here we present an alternative assay that measures the levels of protective antibodies to variant surface antigens (VSA) of IEs. This assay can be performed using a microtitre plate and requires only a small volume of test serum s le. Serum s les are incubated with IEs and are then analyzed using a semi-automated autos ler attached to a flow cytometer. The assay is accurate, quick, and reproducible. Ultimately this assay could be used on large population-based studies, which could increase the statistical power of clinical studies.
Publisher: Elsevier BV
Date: 10-2023
Publisher: American Society for Microbiology
Date: 07-2019
DOI: 10.1128/IAI.00865-18
Abstract: During pregnancy, Plasmodium falciparum -infected erythrocytes (IE) accumulate in the intervillous spaces of the placenta by binding to chondroitin sulfate A (CSA) and elicit inflammatory responses that are associated with poor pregnancy outcomes. Primigravidae lack immunity to IE that sequester in the placenta and thus are susceptible to placental malaria (PM).
Publisher: Frontiers Media SA
Date: 15-03-2021
DOI: 10.3389/FIMMU.2021.621382
Abstract: Pregnant women in malaria-endemic regions are susceptible to malaria in pregnancy, which has adverse consequences on birth outcomes, including having small for gestational age and preterm babies. These babies are likely to have low birthweights, which predisposes to infant mortality and lifelong morbidities. During malaria in pregnancy, Plasmodium falciparum- infected erythrocytes express a unique variant surface antigen, VAR2CSA, that mediates sequestration in the placenta. This process may initiate a range of host responses that contribute to placental inflammation and dysregulated placental development, which affects placental vasculogenesis, angiogenesis and nutrient transport. Collectively, these result in the impairment of placental functions, affecting fetal development. In this review, we provide an overview of malaria in pregnancy and the different pathological pathways leading to malaria in pregnancy-associated low birthweight. We also discuss current prevention and management strategies for malaria in pregnancy, and some potential therapeutic interventions that may improve birth outcomes. Lastly, we outline some priorities for future research that could bring us one step closer to reducing this health burden.
Publisher: Frontiers Media SA
Date: 07-10-2020
Publisher: Springer Science and Business Media LLC
Date: 10-2017
DOI: 10.1038/LABAN.1349
Publisher: Springer Science and Business Media LLC
Date: 19-02-2019
DOI: 10.1038/S41598-019-38821-2
Abstract: Intermittent preventive treatment with sulphadoxine-pyrimethamine (SP) and SP plus azithromycin (SPAZ) reduces low birthweight ( ,500 g) in women without malarial and reproductive tract infections. This study investigates the impact of SPAZ on associations between plasma biomarkers of inflammation and angiogenesis and adverse pregnancy outcomes in 2,012 Papua New Guinean women. Concentrations of C-reactive protein (CRP), α-1-acid glycoprotein (AGP), soluble endoglin (sEng), soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) were measured at enrolment and delivery in a trial comparing SPAZ to SP plus chloroquine (SPCQ). At antenatal enrolment higher CRP (adjusted odds ratio 1.52 95% confidence interval [CI] 1.03–2.25), sEng (4.35 1.77, 10.7) and sFlt1 (2.21 1.09, 4.48) were associated with preterm birth, and higher sEng with low birthweight (1.39 1.11,3.37), in SPCQ recipients only. Increased enrolment sFlt1:PlGF ratios associated with LBW in all women (1.46 1.11, 1.90). At delivery, higher AGP levels were strongly associated with low birthweight, preterm birth and small-for-gestational age babies in the SPCQ arm only. Restricting analyses to women without malaria infection did not materially alter these relationships. Women receiving SPAZ had lower delivery AGP and CRP levels (p 0.001). SPAZ may protect against adverse pregnancy outcomes by reducing inflammation and preventing its deleterious consequences, including dysregulation of placental angiogenesis, in women with and without malarial infection.
Publisher: JMIR Publications Inc.
Date: 13-04-2021
Abstract: xtended reality, which encompasses virtual reality (VR), augmented reality (AR), and mixed reality (MR), is increasingly used in medical education. Studies assessing the effectiveness of these new educational modalities should measure relevant outcomes using outcome measurement tools with validity evidence. ur aim is to determine the choice of outcomes, measurement instruments, and the use of measurement instruments with validity evidence in randomized controlled trials (RCTs) on the effectiveness of VR, AR, and MR in medical student education. e conducted a systematic mapping review. We searched 7 major bibliographic databases from January 1990 to April 2020, and 2 reviewers screened the citations and extracted data independently from the included studies. We report our findings in line with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. f the 126 retrieved RCTs, 115 (91.3%) were on VR and 11 (8.7%) were on AR. No RCT on MR in medical student education was found. Of the 115 studies on VR, 64 (55.6%) were on VR simulators, 30 (26.1%) on screen-based VR, 9 (7.8%) on VR patient simulations, and 12 (10.4%) on VR serious games. Most studies reported only a single outcome and immediate postintervention assessment data. Skills outcome was the most common outcome reported in studies on VR simulators (97%), VR patient simulations (100%), and AR (73%). Knowledge was the most common outcome reported in studies on screen-based VR (80%) and VR serious games (58%). Less common outcomes included participants’ attitudes, satisfaction, cognitive or mental load, learning efficacy, engagement or self-efficacy beliefs, emotional state, competency developed, and patient outcomes. At least one form of validity evidence was found in approximately half of the studies on VR simulators (55%), VR patient simulations (56%), VR serious games (58%), and AR (55%) and in a quarter of the studies on screen-based VR (27%). Most studies used assessment methods that were implemented in a nondigital format, such as paper-based written exercises or in-person assessments where examiners observed performance (72%). CTs on VR and AR in medical education report a restricted range of outcomes, mostly skills and knowledge. The studies largely report immediate postintervention outcome data and use assessment methods that are in a nondigital format. Future RCTs should include a broader set of outcomes, report on the validity evidence of the measurement instruments used, and explore the use of assessments that are implemented digitally.
Publisher: Springer Science and Business Media LLC
Date: 16-07-2021
DOI: 10.1186/S12936-021-03849-1
Abstract: There are seven known species of Plasmodium spp. that can infect humans. The human host can mount a complex network of immunological responses to fight infection and one of these immune functions is phagocytosis. Effective and timely phagocytosis of parasites, accompanied by the activation of a regulated inflammatory response, is beneficial for parasite clearance. Functional studies have identified specific opsonins, particularly antibodies and distinct phagocyte sub-populations that are associated with clinical protection against malaria. In addition, cellular and molecular studies have enhanced the understanding of the immunological pathways and outcomes following phagocytosis of malaria parasites. In this review, an integrated view of the factors that can affect phagocytosis of infected erythrocytes and parasite components, the immunological consequences and their association with clinical protection against Plasmodium spp. infection is provided. Several red blood cell disorders and co-infections, and drugs that can influence phagocytic capability during malaria are also discussed. It is hoped that an enhanced understanding of this immunological process can benefit the design of new therapeutics and vaccines to combat this infectious disease.
No related grants have been discovered for Andrew Teo.