A hybrid model for studying spatial aspects of infectious diseases

We consider a hybrid model, created by coupling a continuum and an agent-based model of infectious disease. The framework of the hybrid model provides a mechanism to study the spread of infection at both the individual and population levels. This approach captures the stochastic spatial heterogeneity at the individual level, which is directly related to deterministic population level properties. This facilitates the study of spatial aspects of the epidemic process. A spatial analysis, involving counting the number of infectious agents in equally sized bins, reveals when the spatial domain is nonhomogeneous.

Transient expression of Human papillomavirus type 16 L1 protein in Nicotiana benthamiana using an infectious tobamovirus vector

A Tobacco mosaic virus (TMV)-derived vector was used to express a native Human papillomavirus type 16 (HPV-16) L1 gene in Nicotiana benthamiana by means of infectious in vitro RNA transcripts inoculated onto N. benthamiana plants. HPV-16 L1 protein expression was quantitated by enzyme-linked immunosorbent assays (ELISA) after concentration of the plant extract. We estimated that the L1 product yield was 20-37 μg/kg of fresh leaf material. The L1 protein in the concentrated extract was antigenically characterised using the neutralising and conformation-specific Mabs H16:V5 and H16:E70, which bound to the plant-produced protein. Particles observed by transmission electron microscopy were mainly capsomers but virus-like particles (VLPs) similar to those produced in other systems were also present. Immunisation of rabbits with the concentrated plant extract induced a weak immune response. This is the first report of the successful expression of an HPV L1 gene in plants using a plant virus vector. © 2006 Elsevier B.V. All rights reserved.

Editorial : infectious disease modelling

The aim of this Special Issue is to collect together a group of outstanding applied mathematics research articles that provide new insight into our understanding of infectious diseases and infectious disease modelling. The scope of the articles is broad, encompassing both specific applications of modelling to particular examples of infectious diseases, as well as articles that are devoted to the development of more general theoretical insight.

Four new avian mitochondrial genomes help get to basic evolutionary questions in the late cretaceous

Good phylogenetic trees are required to test hypotheses about evolutionary processes. We report four new avian mitochondrial genomes, which together with an improved method of phylogenetic analysis for vertebrate mt genomes give results for three questions in avian evolution. The new mt genomes are: magpie goose (Anseranas semipalmata), an owl (morepork, Ninox novaeseelandiae); a basal passerine (rifleman, or New Zealand wren, Acanthisitta chloris); and a parrot (kakapo or owl-parrot, Strigops habroptilus). The magpie goose provides an important new calibration point for avian evolution because the well-studied Presbyornis fossils are on the lineage to ducks and geese, after the separation of the magpie goose. We find, as with other animal mitochondrial genomes, that RY-coding is helpful in adjusting for biases between pyrimidines and between purines. When RY-coding is used at third positions of the codon, the root occurs between paleognath and neognath birds (as expected from morphological and nuclear data). In addition, passerines form a relatively old group in Neoaves, and many modern avian lineages diverged during the Cretaceous. Although many aspects of the avian tree are stable, additional taxon sampling is required.

Development of an integrated metabolomic profiling approach for infectious diseases research

Metabolomic profiling offers direct insights into the chemical environment and metabolic pathway activities at sites of human disease. During infection, this environment may receive important contributions from both host and pathogen. Here we apply an untargeted metabolomics approach to identify compounds associated with an E. coli urinary tract infection population. Correlative and structural data from minimally processed samples were obtained using an optimized LC-MS platform capable of resolving ~2300 molecular features. Principal component analysis readily distinguished patient groups and multiple supervised chemometric analyses resolved robust metabolomic shifts between groups. These analyses revealed nine compounds whose provisional structures suggest candidate infection-associated endocrine, catabolic, and lipid pathways. Several of these metabolite signatures may derive from microbial processing of host metabolites. Overall, this study highlights the ability of metabolomic approaches to directly identify compounds encountered by, and produced from, bacterial pathogens within human hosts.

Beliefs underlying blood donors’ intentions to donate during two phases of an avian influenza outbreak

Using a Theory of Planned Behavior (TPB) framework the current study explored the beliefs of current blood donors (N=172) about donating during a low and high-risk phase of a potential avian influenza outbreak. While the majority of behavioral, normative, and control beliefs identified in preliminary research differed as a function of donors’ intentions to donate during both phases of an avian influenza outbreak, regression analyses suggested that the targeting of different specific beliefs during each phase of an outbreak would yield most benefit in bolstering donors’ intentions to remain donating. The findings provide insight in how to best motivate donors in different phases of an avian influenza outbreak.

Lower respiratory infections in Australian Indigenous children

Despite Australia being one of the wealthiest countries of the world, Australian Indigenous children have a health status and social circumstance comparable to developing countries. Indigenous infants have 10 times the mortality rate for respiratory conditions. The lower respiratory infection (LRI) rate in Australian Indigenous children is at least as high as that of children in developing countries; the frequency of hospitalisations of Indigenous infants is triple that of non-Indigenous Australian infants (201.7 vs. 62.6/1000, respectively). While Indigenous Australian children have many risk factors for LRIs described in developing countries, there is little specific data, and hence, evidence-based intervention points are yet to be identified. Efficacy of conjugate vaccines for common bacterial causes of pneumonia has been less marked in Indigenous children than that documented overseas. Gaps in the management and prevention of disease are glaring. Given the burden of LRI in Indigenous children and the association with long-term respiratory dysfunction, LRIs should be addressed as a matter of priority.

Does a 10-valent pneumococcal-Haemophilus influenzae protein D conjugate vaccine prevent respiratory exacerbations in children with recurrent protracted bacterial bronchitis, chronic suppurative lung disease and bronchiectasis : protocol for a randomised controlled trial

Background Recurrent protracted bacterial bronchitis (PBB), chronic suppurative lung disease (CSLD) and bronchiectasis are characterised by a chronic wet cough and are important causes of childhood respiratory morbidity globally. Haemophilus influenzae and Streptococcus pneumoniae are the most commonly associated pathogens. As respiratory exacerbations impair quality of life and may be associated with disease progression, we will determine if the novel 10-valent pneumococcal-Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) reduces exacerbations in these children. Methods A multi-centre, parallel group, double-blind, randomised controlled trial in tertiary paediatric centres from three Australian cities is planned. Two hundred six children aged 18 months to 14 years with recurrent PBB, CSLD or bronchiectasis will be randomised to receive either two doses of PHiD-CV or control meningococcal (ACYW(135)) conjugate vaccine 2 months apart and followed for 12 months after the second vaccine dose. Randomisation will be stratified by site, age (<6 years and >= 6 years) and aetiology (recurrent PBB or CSLD/bronchiectasis). Clinical histories, respiratory status (including spirometry in children aged >= 6 years), nasopharyngeal and saliva swabs, and serum will be collected at baseline and at 2, 3, 8 and 14 months post-enrolment. Local and systemic reactions will be recorded on daily diaries for 7 and 30 days, respectively, following each vaccine dose and serious adverse events monitored throughout the trial. Fortnightly, parental contact will help record respiratory exacerbations. The primary outcome is the incidence of respiratory exacerbations in the 12 months following the second vaccine dose. Secondary outcomes include: nasopharyngeal carriage of H. influenzae and S. pneumoniae vaccine and vaccine-related serotypes; systemic and mucosal immune responses to H. influenzae proteins and S. pneumoniae vaccine and vaccine-related serotypes; impact upon lung function in children aged >= 6 years; and vaccine safety. Discussion As H. influenzae is the most common bacterial pathogen associated with these chronic respiratory diseases in children, a novel pneumococcal conjugate vaccine that also impacts upon H. influenzae and helps prevent respiratory exacerbations would assist clinical management with potential short- and long-term health benefits. Our study will be the first to assess vaccine efficacy targeting H. influenzae in children with recurrent PBB, CSLD and bronchiectasis.

The use of acoustic indices to determine avian species richness in audio-recordings of the environment

Interpreting acoustic recordings of the natural environment is an increasingly important technique for ecologists wishing to monitor terrestrial ecosystems. Technological advances make it possible to accumulate many more recordings than can be listened to or interpreted, thereby necessitating automated assistance to identify elements in the soundscape. In this paper we examine the problem of estimating avian species richness by sampling from very long acoustic recordings. We work with data recorded under natural conditions and with all the attendant problems of undefined and unconstrained acoustic content (such as wind, rain, traffic, etc.) which can mask content of interest (in our case, bird calls). We describe 14 acoustic indices calculated at one minute resolution for the duration of a 24 hour recording. An acoustic index is a statistic that summarizes some aspect of the structure and distribution of acoustic energy and information in a recording. Some of the indices we calculate are standard (e.g. signal-to-noise ratio), some have been reported useful for the detection of bioacoustic activity (e.g. temporal and spectral entropies) and some are directed to avian sources (spectral persistence of whistles). We rank the one minute segments of a 24 hour recording in descending order according to an "acoustic richness" score which is derived from a single index or a weighted combination of two or more. We describe combinations of indices which lead to more efficient estimates of species richness than random sampling from the same recording, where efficiency is defined as total species identified for given listening effort. Using random sampling, we achieve a 53% increase in species recognized over traditional field surveys and an increase of 87% using combinations of indices to direct the sampling. We also demonstrate how combinations of the same indices can be used to detect long duration acoustic events (such as heavy rain and cicada chorus) and to construct long duration (24 h) spectrograms.

Infectious in vitro transcripts from a cloned cDNA of barley yellow dwarf virus

A full-length cDNA clone of barley yellow dwarf virus (BYDV-PAV serotype) has been constructed and fused to the bacteriophage T7 RNA polymerase promoter. RNA transcripts produced in vitro, either capped or uncapped, were infectious in Triticum monococcum protoplasts. Protoplasts inoculated with in vitro-transcribed BYDV RNA accumulated coat protein, synthesized new viral RNAs, and produced virus particles. Aphid feeding on extracts from protoplasts inoculated with in vitro RNA transcripts can be used to transfer the virus progeny to whole plants. Introduction of mutations which interrupt specific BYDV-PAV open reading frames (ORFs) V and VI eliminated infectivity while an ORF I mutant remained infectious. Infectious RNA transcripts derived from BYDV cDNA clones will facilitate analysis of the molecular aspects of BYDV infection and further enhance our understanding of this economically important virus.

Internet-based surveillance systems for monitoring emerging infectious diseases

Emerging infectious diseases present a complex challenge to public health officials and governments; these challenges have been compounded by rapidly shifting patterns of human behaviour and globalisation. The increase in emerging infectious diseases has led to calls for new technologies and approaches for detection, tracking, reporting, and response. Internet-based surveillance systems offer a novel and developing means of monitoring conditions of public health concern, including emerging infectious diseases. We review studies that have exploited internet use and search trends to monitor two such diseases: influenza and dengue. Internet-based surveillance systems have good congruence with traditional surveillance approaches. Additionally, internet-based approaches are logistically and economically appealing. However, they do not have the capacity to replace traditional surveillance systems; they should not be viewed as an alternative, but rather an extension. Future research should focus on using data generated through internet-based surveillance and response systems to bolster the capacity of traditional surveillance systems for emerging infectious diseases.

Epidemiologic characteristics of cases for influenza A(H7N9) virus infections in China

China's National Health and Family Planning Commission announced 3 deaths caused by avian-origin influenza A(H7N9) virus in March, which was the first time that the H7N9 strain has been found in humans [1]. This is of major public health significance and raises urgent questions and global concerns [2, 3]. To explore epidemic characteristics of human infections with H7N9 virus, data on individual cases from 19 February 2013 (onset date of first case) to 14 April 2013 were collected from the China Information System for Disease Control and Prevention, which included information about sex; age; occupation; residential address; and day of symptom onset, diagnosis, and outcome for each case. The definition of an unconfirmed probable H7N9 case is a patient with epidemiologic evidence of contact …

Asthma and protracted bronchitis : who fares better during an acute respiratory infection?

Aim Acute respiratory infections (ARI) are common in children, and symptoms range from days to weeks. The aim of this study was to determine if children with asthma have more severe ARI episodes compared with children with protracted bronchitis and controls. Methods Parents prospectively scored their child's next ARI using the Canadian acute respiratory illness and flu scale (CARIFS) and a validated cough diary (on days 1–7, 10 and 14 of illness). Children were age- and season-matched. Results On days 10 and 14 of illness, children with protracted bronchitis had significantly higher median CARIFS when compared with children with asthma and healthy controls. On day 14, the median CARIFS were: asthma = 4.1 (interquartile range (IQR) 4.0), protracted bronchitis = 19.6 (IQR 25.8) and controls = 4.1 (IQR 5.25). The median cough score was significantly different between groups on days 1, 7, 10 and 14 (P < 0.001). A significantly higher proportion of children with protracted bronchitis (63%) were still coughing at day 14 in comparison with children with asthma (24%) and healthy controls (26%). Conclusion Children with protracted bronchitis had the most severe ARI symptoms and higher percentage of respiratory morbidity at day 14 in comparison with children with asthma and healthy controls.

A systematic review of community-based interventions for emerging zoonotic diseases in Southeast Asia

Background Southeast Asia has been at the epicentre of recent epidemics of emerging and re-emerging zoonotic diseases. Community-based surveillance and control interventions have been heavily promoted but the most effective interventions have not been identified. Objectives This review evaluated evidence for the effectiveness of community-based surveillance interventions at monitoring and identifying emerging infectious disease; the effectiveness of community-based control interventions at reducing rates of emerging infectious disease; and contextual factors that influence intervention effectiveness. Inclusion criteria Participants Communities in Brunei, Cambodia, Indonesia, Laos, Malaysia, Myanmar, the Philippines, Singapore, Thailand and Viet Nam. Types of intervention(s) Non-pharmaceutical, non-vaccine, and community-based surveillance or prevention and control interventions targeting rabies, Nipah virus , dengue, SARS or avian influenza. Types of outcomes Primary outcomes: measures: of infection or disease; secondary outcomes: measures of intervention function. Types of studies Original quantitative studies published in English. Search strategy Databases searched (1980 to 2011): PubMed, CINAHL, ProQuest, EBSCOhost, Web of Science, Science Direct, Cochrane database of systematic reviews, WHOLIS, British Development Library, LILACS, World Bank (East Asia), Asian Development Bank. Methodological quality Two independent reviewers critically appraised studies using standard Joanna Briggs Institute instruments. Disagreements were resolved through discussion. Data extraction A customised tool was used to extract quantitative data on intervention(s), populations, study methods, and primary and secondary outcomes; and qualitative contextual information or narrative evidence about interventions. Data synthesis Data was synthesised in a narrative summary with the aid of tables. Meta-analysis was used to statistically pool quantitative results. Results Fifty-seven studies were included. Vector control interventions using copepods, environmental cleanup and education are effective and sustainable at reducing dengue in rural and urban communities, whilst insecticide spraying is effective in urban outbreak situations. Community-based surveillance interventions can effectively identify avian influenza in backyard flocks, but have not been broadly applied. Outbreak control interventions for Nipah virus and SARS are effective but may not be suitable for ongoing control. Canine vaccination and education is more acceptable than culling, but still fails to reach coverage levels required to effectively control rabies. Contextual factors were identified that influence community engagement with, and ultimately effectiveness of, interventions. Conclusion Despite investment in community-based disease control and surveillance in Southeast Asia, published evidence evaluating interventions is limited in quantity and quality. Nonetheless this review identified a number of effective interventions, and several contextual factors influencing effectiveness. Identification of the best programs will require comparative evidence of effectiveness acceptability, cost-effectiveness and sustainability.