Applied epidemiology of vaccine-preventable diseases in the Asia-Pacific

From 2015-2016 I undertook the Master of Philosophy in Applied Epidemiology (MAE) whilst under the employment of the Murdoch Childrens Research Institute (MCRI) in Melbourne as a research officer for a study based in the People’s Democratic Republic of Laos (Lao PDR). To satisfy the requirements of the MAE, I completed projects in the areas of data analysis, public health surveillance, epidemiological research and outbreak investigation. The work I was employed for with MCRI formed the basis of my data analysis competency. The aim of this project was to determine the pneumococcal conjugate vaccine (PCV) coverage required to achieve herd immunity using pneumococcal carriage surveillance at Mahosot Hospital in Lao PDR. Beyond the analysis of these data, I was responsible for overseeing and coordinating the larger body of work for this project based in Lao PDR. This work is ongoing and a final publication will be published later in 2017. With guidance from my field supervisor, I was responsible for establishing the epidemiology of acute gastroenteritis (AGE) in Kiribati pre- and post-rotavirus (RV) vaccine introduction. As part of this review, I established post-marketing surveillance of intussusception (IS) as part of RV vaccine introduction. The World Health Organization (WHO) recommends the surveillance of IS post-RV vaccine introduction due to experiences with a previous formulation of the vaccine. This evaluation is ongoing and will be completed in 2017. In response to vaccine preventable disease (VPD) outbreaks in Lao PDR, the Ministry of Health, National Immunization Programme (NIP) requested information regarding evidence of serological protection of H. influenzae type b (Hib) in their population. This study was the basis of my epidemiological research for the MAE. The results from this study would provide data on Hib protection in their population to help inform NIP if changes to their current schedule were necessary. For my outbreak investigation competency, I was involved with the team at WHO Lao PDR country office in responding to a circulating vaccine-derived poliovirus type 1 (cVDPV1) outbreak in Lao PDR from October 2015 to mid-2017. As part of this work I will contribute to the outbreak investigation section of the larger WHO report to be submitted to NIP. This thesis presents my experience as a MAE scholar; the skills gained, knowledge learnt and the impact this body of work had on public health in the Asia-Pacific region for VPD. Keywords: Vaccine-preventable disease, Laos PDR, pneumococcal conjugate vaccine, Kiribati, intussusception, rotavirus vaccine, Haemophilus influenzae type b, vaccination evidence, serology, poliovirus, circulating vaccine-derived polioviru

A chromosomal genomics approach to assess and validate the desi and kabuli draft chickpea genome assemblies

With the expansion of next-generation sequencing technology and advanced bioinformatics, there has been a rapid growth of genome sequencing projects. However, while this technology enables the rapid and cost-effective assembly of draft genomes, the quality of these assemblies usually falls short of gold standard genome assemblies produced using the more traditional BAC by BAC and Sanger sequencing approaches. Assembly validation is often performed by the physical anchoring of genetically mapped markers, but this is prone to errors and the resolution is usually low, especially towards centromeric regions where recombination is limited. New approaches are required to validate reference genome assemblies. The ability to isolate individual chromosomes combined with next-generation sequencing permits the validation of genome assemblies at the chromosome level. We demonstrate this approach by the assessment of the recently published chickpea kabuli and desi genomes. While previous genetic analysis suggests that these genomes should be very similar, a comparison of their chromosome sizes and published assemblies highlights significant differences. Our chromosomal genomics analysis highlights short defined regions that appear to have been misassembled in the kabuli genome and identifies large-scale misassembly in the draft desi genome. The integration of chromosomal genomics tools within genome sequencing projects has the potential to significantly improve the construction and validation of genome assemblies. The approach could be applied both for new genome assemblies as well as published assemblies, and complements currently applied genome assembly strategies

The effectiveness of the 13-valent pneumococcal conjugate vaccine against hypoxic pneumonia in children in Lao People's Democratic Republic: An observational hospital-based test-negative study

Background: Pneumococcal pneumonia is a leading cause of childhood mortality. Pneumococcal conjugate vaccines (PCVs) have been shown to reduce hypoxic pneumonia in children. However, there are no studies from Asia examining the effectiveness of PCVs on hypoxic pneumonia. We describe a novel approach to determine the effectiveness of the 13-valent PCV (PCV13) against hypoxia in children admitted with pneumonia in the Lao People's Democratic Republic. Methods: A prospective hospital-based, test-negative observational study of children aged up to 59 months admitted with pneumonia to a single tertiary hospital in Vientiane was undertaken over 54 months. Pneumonia was defined using the 2013 WHO definition. Hypoxia was defined as oxygen saturation <90% in room air or requiring oxygen supplementation during hospitalisation. Test-negative cases and controls were children with hypoxic and non-hypoxic pneumonia, respectively. PCV13 status was determined by written record. Vaccine effectiveness was calculated using logistic regression. Propensity score and multiple imputation analyses were used to handle confounding and missing data. Findings: There were 826 children admitted with pneumonia, 285 had hypoxic pneumonia and 377 were PCV13-vaccinated. The unadjusted, propensity-score adjusted and multiple-imputation adjusted estimates of vaccine effectiveness against hypoxic pneumonia were 23% (95% confidence interval: -9, 46%; p=0•14); 37% (6, 57%; p=0•02) and 35% (7, 55%; p=0•02) respectively. Interpretation: PCV13 is effective against hypoxic pneumonia in Asia, and should be prioritised for inclusion in national immunisation programs. This single hospital-based, test-negative approach can be used to assess vaccine effectiveness in other similar settings. Funding: Funded by the Bill & Melinda Gates Foundation

Towards a classification strategy for complex nanostructures

The range of possible nanostructures is so large and continuously growing, that collating and unifying the knowledge connected to them, including their biological activity, is a major challenge. Here we discuss a conception that is based on connection of microscopic features of the nanomaterials to their biological impacts. We also consider what would be necessary to identify the features that control their biological interactions, and make them resemble each other in a biological context

Acute respiratory infections in hospitalized children in Vientiane, Lao PDR - the importance of Respiratory Syncytial Virus

The Human respiratory syncytial virus (RSV) is one of the most important viral pathogens, causing epidemics of acute respiratory infection (ARI), especially bronchiolitis and pneumonia, in children worldwide. To investigate the RSV burden in Laos, we conducted a one-year study in children <5 years old admitted to Mahosot Hospital, Vientiane Capital, to describe clinical and epidemiological characteristics and predictive factors for severity of RSV-associated ARI. Pooled nasal and throat swabs were tested using multiplex real-time PCR for 33 respiratory pathogens (FTD® kit). A total of 383 patients were included, 277 (72.3%) of whom presented with pneumonia. 377 (98.4%) patients were positive for at least one microorganism, of which RSV was the most common virus (41.0%), with a peak observed between June and September, corresponding to the rainy season. Most RSV inpatients had pneumonia (84.1%), of whom 35% had severe pneumonia. Children <3-months old were a high-risk group for severe pneumonia, independently of RSV infection. Our study suggests that RSV infection is frequent in Laos and commonly associated with pneumonia in hospitalized young children. Further investigations are required to provide a better overall view of the Lao nationwide epidemiology and public health burden of RSV infection over time.This study was funded by the Institute of Research for Development (IRD), Aix-Marseille University, the Wellcome Trust of Great Britain (Grant number 089275/H/09/Z0). Te feldwork was supported by the Bill & Melinda Gates Foundation grant OPP1115490 and the Murdoch Childrens Research Institute, Melbourne, Australia. Te authors declare that no competing interests exist

Photo-induced antibacterial activity of four graphene based nanomaterials on a wide range of bacteria

Due to controversial reports concerning antibacterial activity of different graphene based materials it is very important to investigate their antibacterial action on a wide range of Gram-positive and Gram-negative bacteria. In this paper we have investigated the structure induced phototoxic antibacterial activity of four types of graphene based materials: graphene oxide (GO), graphene quantum dots (GQDs), carbon quantum dots (CQDs) and nitrogen doped carbon quantum dots (N-CQDs). Antibacterial activity was tested on 19 types of bacteria. It is found that nanometer-size CQDs and N-CQDs are the most potent agents whereas micrometer-size GO has very poor antibacterial activity. Electron paramagnetic resonance measurements confirmed photodynamic production of singlet oxygen for all types of used quantum dots. Detailed analysis has shown that N-CQDs are an excellent photodynamic antibacterial agent for treatment of bacterial infections induced by Enterobacter aerogenes (E. aerogenes), Proteus mirabilis (P. mirabilis), Staphylococcus saprophyticus (S. saprophyticus), Listeria monocytogenes (L. monocytogenes), Salmonella typhimurium (S. typhimurium) and Klebsiella pneumoniae

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 7 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal