The cost of community-managed viral respiratory illnesses in a cohort of healthy preschool-aged children

Background : Acute respiratory illnesses (ARIs) during childhood are often caused by respiratory viruses, result in significant morbidity, and have associated costs for families and society. Despite their ubiquity, there is a lack of interdisciplinary epidemiologic and economic research that has collected primary impact data, particularly associated with indirect costs, from families during ARIs in children.
Methods : We conducted a 12-month cohort study in 234 preschool children with impact diary recording and PCR testing of nose-throat swabs for viruses during an ARI. We used applied values to estimate a virus-specific mean cost of ARIs.
Results : Impact diaries were available for 72% (523/725) of community-managed illnesses between January 2003 and January 2004. The mean cost of ARIs was AU$309 (95% confidence interval $263 to $354). Influenza illnesses had a mean cost of $904, compared with RSV, $304, the next most expensive single-virus illness, although confidence intervals overlapped. Mean carer time away from usual activity per day was two hours for influenza ARIs and between 30 and 45 minutes for all other ARI categories.
Conclusion : From a societal perspective, community-managed ARIs are a significant cost burden on families and society. The point estimate of the mean cost of community-managed influenza illnesses in healthy preschool aged children is three times greater than those illnesses caused by RSV and other respiratory viruses. Indirect costs, particularly carer time away from usual activity, are the key cost drivers for ARIs in children. The use of parent-collected specimens may enhance ARI surveillance and reduce any potential Hawthorne effect caused by compliance with study procedures. These findings reinforce the need for further integrated epidemiologic and economic research of ARIs in children to allow for comprehensive cost-effectiveness assessments of preventive and therapeutic options.

Tuberculosis associated with household crowding in a developed country

Background: Tuberculosis (TB) remains an important infectious disease in New Zealand (NZ) and globally, but risk factors for transmission are still poorly understood. This research aimed to identify whether household crowding contributes to TB transmission in NZ.

Methods: This ecological study used TB surveillance and census data to calculate TB incidence rates by census area unit (CAU). Census data were used to determine CAU characteristics including proportion of household crowding (a bedroom deficit of one or more), proportion of population who are migrants born in high-TB-incidence countries, median household income, and deprivation level. A negative binomial regression model was used to estimate the association between TB incidence and household crowding.

Results: The analysis included 1898 notified TB cases for the 2000–4 period. Univariate analysis showed TB incidence at the CAU level was associated with household crowding, for the total population and for all ethnic and age groups. After adjusting for the covariates of household income, existing TB burden, and proportion of migrants from high-TB-incidence countries, multivariate analysis showed statistically significant associations between TB incidence and household crowding. The incidence rate ratio (IRR) was 1.05 (95% CI 1.02 to 1.08) in the total population and 1.08 (95% CI 1.04 to 1.12) for NZ-born people <40 years.

Conclusion: At the CAU level, TB incidence in NZ is associated with household crowding. An individual-based study (e.g. case–control) in recently infected cases (detected by molecular epidemiology techniques) is suggested to complement these findings. Reducing or eliminating household crowding could decrease TB incidence in NZ and globally.

Antibiotic resistance in invasive Streptococcus pneumoniae isolates identified in Scotland between 1999 and 2007

Data from 4727 invasive isolates of Streptococcus pneumoniae submitted to the Scottish Haemophilus, Legionella, Meningococcus and Pneumococcus Reference Laboratory between 1999 and 2007 were analysed to establish susceptibility profiles to penicillin, erythromycin and cefotaxime. Pneumococcal resistance to penicillin over the study period remained low, with only 0.2 % (n=7/4727) of isolates falling into this category (MIC ≥2 mg l−1). These isolates have been sporadic, and have mainly represented serogroup 14 (ST9) and 9 (ST156). In comparison, the ‘intermediate sensitivity’ group (MIC 0.12–1 mg l−1) ranged between 2 and 6 % per year, the majority from serogroup 9 (ST156). Over the study period, we found that 12 % (n=585/4727) of isolates were erythromycin-resistant (MIC >0.5 mg l−1), with the majority (n=467; 80 %) of these isolates identified as serogroup 14 (ST9). Cephalosporin resistance (cefotaxime MIC >1 mg l−1) was found in only 0.06 % (n=2/3135) of isolates. Internationally recognized clones (Pneumococcal Molecular Epidemiology Network) accounted for 35 % (n=28/81) of the penicillin non-susceptible isolates and 75 % (n=248/330) of the macrolide-resistant isolates, with ST9 and ST306 predominating. Between 1999 and 2007 we found that 11.6 % (n=18/155) of the penicillin non-susceptible isolates and 4.8 % (n=28/585) of the macrolide-resistant isolates were from serogroups not covered by the 7-valent conjugate pneumococcal vaccine in use in the UK since 2006. Susceptibility to first-line antimicrobial agents for invasive pneumococcal disease in Scotland remained high over the period 1999–2007.

Australian Enterococcal Sepsis Outcome Programme, 2011

From 1 January to 31 December 2011, 29 institutions around Australia participated in the Australian Enterococcal Sepsis Outcome Programme (AESOP). The aim of AESOP 2011 was to determine the proportion of enterococcal bacteraemia isolates in Australia that are antimicrobial resistant, with particular emphasis on susceptibility to ampicillin and the glycopeptides, and to characterise the molecular epidemiology of the Enterococcus faecalis and E. faecium isolates. Of the 1,079 unique episodes of bacteraemia investigated, 95.8% were caused by either E. faecalis (61.0%) or E. faecium (34.8%). Ampicillin resistance was detected in 90.4% of E. faecium but not detected in E. faecalis. Using Clinical and Laboratory Standards Institute breakpoints (CLSI), vancomycin non-susceptibility was reported in 0.6% and 31.4% of E. faecalis and E. faecium respectively and was predominately due to the acquisition of the vanB operon. Approximately 1 in 6 vanB E. faecium isolates however, had an minimum inhibitory concentration at or below the CLSI vancomycin susceptible breakpoint of ≤ 4 mg/L. Overall, 37% of E. faecium harboured vanA or vanB genes. Although molecular typing identified 126 E. faecalis pulsed-field gel electrophoresis (PFGE) pulsotypes, more than 50% belonged to 2 pulsotypes that were isolated across Australia. E. faecium consisted of 73 PFGE pulsotypes from which 43 multilocus sequence types were identified. Almost 90% of the E. faecium were identified as clonal complex 17 clones, of which approximately half were characterised as sequence type 203, which was isolated Australia-wide. In conclusion, the AESOP 2011 has shown that although polyclonal, enterococcal bacteraemias in Australia are frequently caused by ampicillin-resistant vanB E. faecium.

Outdoor fungi and child asthma health service attendances

Asthma is a significant global public health issue. Severe asthma exacerbations can be triggered by environmental factors and require medical care from health services. Although it is known that fungal exposure may lead to allergic sensitization, little is understood about its impact on asthma exacerbations. This review aims to examine whether outdoor fungi play a significant role in child asthma exacerbations. Systematic search of seven electronic databases and hand searching for peer-reviewed studies published in English, up to 31 August 2013. Inclusion criteria were study population aged <18 yr, diagnosis of asthma, attended a health service; outdoor fungi exposure was reported. Quality and risk of bias assessments were conducted. Due to significant heterogeneity, meta-analysis was not conducted. Of the 1896 articles found, 15 were eligible. Findings were not consistent, possibly due to methodological variations in exposure classifications, statistical methods and inclusion of confounders. Cross-sectional studies found no or weak associations. All but one time series studies indicated an association that varied between fungal species. Increasing evidence indicates that asthmatic children are susceptible to asthma exacerbations when exposed to outdoor fungal spores. There is limited understanding of the contributions of different fungal species. Research is needed to investigate interactions of outdoor fungi with pollen, air pollutants and respiratory viruses.

Australian Enterococcal Sepsis Outcome Programme annual report, 2013.

From 1 January to 31 December 2013, 26 institutions around Australia participated in the Australian Enterococcal Sepsis Outcome Programme (AESOP). The aim of AESOP 2013 was to determine the proportion of enterococcal bacteraemia isolates in Australia that are antimicrobial resistant, and to characterise the molecular epidemiology of the Enterococcus faecium isolates. Of the 826 unique episodes of bacteraemia investigated, 94.6% were caused by either E. faecalis (56.1%) or E. faecium (38.5%). Ampicillin resistance was not detected in E. faecalis but was detected in over 90% of E. faecium. Vancomycin non-susceptibility was reported in 0.2% and 40.9% of E. faecalis and E. faecium respectively and was predominately due to the acquisition of the vanB operon. Overall, 41.6% of E. faecium harboured vanA or vanB genes. The percentage of E. faecium bacteraemia isolates resistant to vancomycin in Australia is significantly higher than that seen in most European countries. E. faecium isolates consisted of 81 pulsed-field gel electrophoresis pulsotypes of which 72.3% were classified into 14 major pulsotypes containing five or more isolates. Multilocus sequence typing grouped the 14 major pulsotypes into clonal cluster 17, a major hospital-adapted polyclonal E. faecium cluster. Of the 2 predominant sequence types, ST203 (80 isolates) was identified across Australia and ST555 (40 isolates) was isolated primarily in the western and central regions (Northern Territory, South Australia and Western Australia) respectively. In conclusion, the AESOP 2013 has shown enterococcal bacteraemias in Australia are frequently caused by polyclonal ampicillin-resistant high-level gentamicin resistant vanB E. faecium, which have limited treatment options.

Sequence type 131 fimH30 and fimH41 subclones amongst escherichia coli isolates in Australia and New Zealand

The clonal composition of Escherichia coli causing extra-intestinal infections includes ST131 and other common uropathogenic clones. Drivers for the spread of these clones and risks for their acquisition have been difficult to define. In this study, molecular epidemiology was combined with clinical data from 182 patients enrolled in a case-control study of community-onset expanded-spectrum cephalosporin-resistant E. coli (ESC-R-EC) in Australia and New Zealand. Genetic analysis included antimicrobial resistance mechanisms, clonality by DiversiLab (rep-PCR) and multilocus sequence typing (MLST), and subtyping of ST131 by identification of polymorphisms in the fimH gene. The clonal composition of expanded-spectrum cephalosporin-susceptible E. coli and ESC-R-EC isolates differed, with six MLST clusters amongst susceptible isolates (median 7 isolates/cluster) and three clusters amongst resistant isolates, including 40 (45%) ST131 isolates. Population estimates indicate that ST131 comprises 8% of all E. coli within our population; the fluoroquinolone-susceptible H41 subclone comprised 4.5% and the H30 subclone comprised 3.5%. The H30 subclone comprised 39% of all ESC-R-EC and 41% of all fluoroquinolone-resistant E. coli within our population. Patients with ST131 were also more likely than those with non-ST131 isolates to present with an upper than lower urinary tract infection (RR=1.8, 95% CI 1.01-3.1). ST131 and the H30 subclone were predominant amongst ESC-R-EC but were infrequent amongst susceptible isolates where the H41 subclone was more prevalent. Within our population, the proportional contribution of ST131 to fluoroquinolone resistance is comparable with that of other regions. In contrast, the overall burden of ST131 is low by global standards.

The cost of seasonal respiratory illnesses in Australian children: the dominance of patient and family costs and implications for vaccine use

Respiratory viral infections are one of the next group of diseases likely to be targeted for prevention in childhood by the use of vaccines. To begin collecting necessary epidemiology and cost information about the illnesses caused by these viruses, we conducted a prospective cohort study in 118 Melbourne children between 12 and 71 months of age during winter and spring 2001. We were interested in calculating an average cost per episode of community-managed acute respiratory disease, in identifying the key cost drivers of such illness, and to identify the proportion of costs borne by the patient and family. There were 202 community-managed influenza-like illnesses identified between July and December 2001, generating 89 general practitioner visits, and 42 antibiotic prescriptions. The average cost of community-managed episodes (without hospitalisation) was $241 (95% CI $191 to $291), with the key cost drivers being carer time away from usual activities caring for the ill child (70% of costs), use of non-prescription medications (5.4%), and general practice visits (5.0%). The patient and family met 87per cent of total costs. The lowest average cost occurred in households from the highest income bracket. Acute respiratory illness managed in the community is common, with the responsibility for meeting the cost of episodes predominantly borne by the patient and family in the form of lost productivity. These findings have implications for preventive strategies in children, such as the individual use of, or implementation of public programs using, currently available vaccines against influenza and vaccines under development against other viral respiratory pathogens.

Viral RNA silencing suppressors (RSS) : novel strategy of viruses to ablate the host RNA interference (RNAi) defense system

Pathogenic viruses have developed a molecular defense arsenal for their survival by counteracting the host anti-viral system known as RNA interference (RNAi). Cellular RNAi, in addition to regulating gene expression through microRNAs, also serves as a barrier against invasive foreign nucleic acids. RNAi is conserved across the biological species, including plants, animals and invertebrates. Viruses in turn, have evolved mechanisms that can counteract this anti-viral defense of the host. Recent studies of mammalian viruses exhibiting RNA silencing suppressor (RSS) activity have further advanced our understanding of RNAi in terms of host–virus interactions. Viral proteins and non-coding viral RNAs can inhibit the RNAi (miRNA/siRNA) pathway through different mechanisms. Mammalian viruses having dsRNA-binding regions and GW/WG motifs appear to have a high chance of conferring RSS activity. Although, RSSs of plant and invertebrate viruses have been well characterized, mammalian viral RSSs still need in-depth investigations to present the concrete evidences supporting their RNAi ablation characteristics. The information presented in this review together with any perspective research should help to predict and identify the RSS activity-endowed new viral proteins that could be the potential targets for designing novel anti-viral therapeutics.

Identifying crucial gaps in our knowledge of the life-history of avian influenza viruses - An Australian perspective

We review our current knowledge of the epidemiology and ecology of avian influenza viruses (AIVs) in Australia in relation to the ecology of their hosts. Understanding the transmission and maintenance of low-pathogenic avian influenza (LPAI) viruses deserves scientific scrutiny because some of these may evolve to a high-pathogenic AIV (HPAI) phenotype. That the HPAI H5N1 has not been detected in Australia is thought to be a result of the low level of migratory connectivity between Asia and Australia. Some AIV strains are endemic to Australia, with Australian birds acting as a reservoir for these viruses. However, given the phylogenetic relationships between Australian and Eurasian strains, both avian migrants and resident birds within the continent must play a role in the ecology and epidemiology of AIVs in Australia. The extent to which individual variation in susceptibility to infection, previous infections, and behavioural changes in response to infection determine AIV epidemiology is little understood. Prevalence of AIVs among Australian avifauna is apparently low but, given their specific ecology and Australian conditions, prevalence may be higher in little-researched species and under specific environmental conditions.

Migratory birds reinforce local circulation of avian influenza viruses

Migratory and resident hosts have been hypothesized to fulfil distinct roles in infectious disease dynamics. However, the contribution of resident and migratory hosts to wildlife infectious disease epidemiology, including that of low pathogenic avian influenza virus (LPAIV) in wild birds, has largely remained unstudied. During an autumn H3 LPAIV epizootic in free-living mallards (Anas platyrhynchos) - a partially migratory species - we identified resident and migratory host populations using stable hydrogen isotope analysis of flight feathers. We investigated the role of migratory and resident hosts separately in the introduction and maintenance of H3 LPAIV during the epizootic. To test this we analysed (i) H3 virus kinship, (ii) temporal patterns in H3 virus prevalence and shedding and (iii) H3-specific antibody prevalence in relation to host migratory strategy. We demonstrate that the H3 LPAIV strain causing the epizootic most likely originated from a single introduction, followed by local clonal expansion. The H3 LPAIV strain was genetically unrelated to H3 LPAIV detected both before and after the epizootic at the study site. During the LPAIV epizootic, migratory mallards were more often infected with H3 LPAIV than residents. Low titres of H3-specific antibodies were detected in only a few residents and migrants. Our results suggest that in this LPAIV epizootic, a single H3 virus was present in resident mallards prior to arrival of migratory mallards followed by a period of virus amplification, importantly associated with the influx of migratory mallards. Thus migrants are suggested to act as local amplifiers rather than the often suggested role as vectors importing novel strains from afar. Our study exemplifies that a multifaceted interdisciplinary approach offers promising opportunities to elucidate the role of migratory and resident hosts in infectious disease dynamics in wildlife.

Epidemiology of early Rapid Response Team activation after emergency department admission

BACKGROUND: Rapid Response Team (RRT) calls can often occur within 24h of hospital admission to a general ward. We seek to determine whether it is possible to identify these patients before there is a significant clinical deterioration. METHODS: Retrospective case-controlled study comparing patient characteristics, vital signs, and hospital outcomes in patients triggering RRT activation within 24h of ED admission (cases) with matched ED admissions not receiving a RRT call (controls). RESULTS: Over 12 months, there were 154 early RRT calls. Compared with controls, cases had a higher heart rate (HR) at triage (92 vs. 84beats/min; p=0.008); after 3h in the ED (91 vs. 80beats/min; p=0.0007); and at ED discharge (91 vs. 81beats/min; p=0.0005). Respiratory rate (RR) was also higher at triage (21.2 vs. 19.2breaths/min; p=0.001). On multiple variable analysis, RR at triage and HR before ward transfer predicted early RRT activation: OR 1.07 [95% CI 1.02-1.12] for each 1breath/min increase in RR; and 1.02 [95% CI 1.002-1.030] for each beat/minute increase in HR, respectively. Study patients required transfer to the intensive care in approximately 20% of cases and also had a greater mortality: (21% vs. 6%; OR 4.65 [95% CI 1.86-11.65]; p=0.0003) compared with controls. CONCLUSIONS: Patients that trigger RRT calls within 24h of admission have a fourfold increase in risk of in-hospital mortality. Such patients may be identified by greater tachycardia and tachypnoea in the ED.

Molecular targets in arthritis and recent trends in nanotherapy

Due to its severity and increasing epidemiology, arthritis needs no description. There are various forms of arthritis most of which are disabling, very painful, and common. In spite of breakthroughs in the field of drug discovery, there is no cure for arthritis that can eliminate the disease permanently and ease the pain. The present review focuses on some of the most successful drugs in arthritis therapy and their side effects. Potential new targets in arthritis therapy such as interleukin-1β, interleukin-17A, tumor necrosis factor alpha, osteopontin, and several others have been discussed here, which can lead to refinement of current therapeutic modalities. Mechanisms for different forms of arthritis have been discussed along with the molecules that act as potential biomarkers for arthritis. Due to the difficulty in monitoring the disease progression to detect the advanced manifestations of the diseases, drug-induced cytotoxicity, and problems with drug delivery; nanoparticle therapy has gained the attention of the researchers. The unique properties of nanoparticles make them highly attractive for the design of novel therapeutics or diagnostic agents for arthritis. The review also focuses on the recent trends in nanoformulation development used for arthritis therapy. This review is, therefore, important because it describes the relevance and need for more arthritis research, it brings forth a critical discussion of successful drugs in arthritis and analyses the key molecular targets. The review also identifies several knowledge gaps in the published research so far along with the proposal of new ideas and future directions in arthritis therapy.

The epidemiology of sepsis during rapid response team reviews in a teaching hospital

In a three-month retrospective study, we assessed the proportion of rapid response team (RRT) calls associated with systemic inflammatory response syndrome (SIRS) and sepsis. We also documented the site of infection (whether it was community- or hospital-acquired), antibiotic modifications after the call and in-hospital outcomes. Amongst 358 RRT calls, two or more SIRS criteria were present in 277 (77.4%). Amongst the 277 RRT calls with SIRS criteria, 159 (57.4%) fulfilled sepsis criteria in the 24 hours before and 12 hours after the call. There were 118 of 277 (42.6%) calls with SIRS criteria but no evidence of sepsis and 62 of 277 (22.3%) calls associated with both criteria for sepsis as well as an alternative cause for SIRS. Hence, 159 (44.4%) of all 358 RRT calls over the three-month study period fulfilled criteria for sepsis and in 97 (159-62) (27.1%) of the 358 calls, there were criteria for sepsis without other causes for SIRS criteria. The most common sites of infection were respiratory tract (86), abdominal cavity (38), urinary tract (26) and bloodstream (26). Infection was hospital-acquired in 91 (57.2%) and community-acquired in 67 (42.1%) cases, respectively. Patients were on antibiotics in 127 of 159 (79.9%) cases before the RRT call and antibiotics were added or modified in 76 of 159 (47.8%) cases after RRT review. The hospital length-of-stay of patients who received an RRT call associated with sepsis was longer than those who did not (16.0 [8.0 to 28.5] versus 10 days [6.0 to 18.0]; P=0.002).