Implementation guide for surveillance of Clostridium difficile infection

The Implementation Guide for hospital surveillance of Clostridium difficile infection (CDI) has been produced by the Healthcare Associated Infection (HAI) Technical Working Group of the Australian Commission on Safety and Quality in Health Care (ACSQHC), and endorsed by the HAI Advisory Group. State jurisdictions and the ACSQHC have representatives on the Technical Working Group, and have had input into this document. The Guide is intended to be used by Australian hospitals and organisations to support the implementation of hospital-identified Clostridium difficile infection (CDI) surveillance using the endorsed case definition in this guide. It has been produced to support consistency of surveillance activities and is not intended to replace clinical assessment of infection for patient management.

Mailed versus frozen transport of nasal swabs for surveillance of respiratory bacteria in remote Indigenous communities in Australia

Background Surveillance programs and research for acute respiratory infections in remote Australian communities are complicated by difficulties in the storage and transport of frozen samples to urban laboratories for testing. This study assessed the sensitivity of a simple method for transporting nasal swabs from a remote setting for bacterial polymerase chain reaction (PCR) testing. Methods We sampled every individual who presented to a remote community clinic over a three week period in August at a time of low influenza and no respiratory syncytial virus activity. Two anterior nasal swabs were collected from each participant. The left nare specimen was mailed to the laboratory via routine postal services. The right nare specimen was transported frozen. Testing for six bacterial species was undertaken using real-time PCR. Results One hundred and forty participants were enrolled who contributed 150 study visits and paired specimens for testing. Respiratory illnesses accounted for 10% of the reasons for presentation. Bacteria were identified in 117 (78%) presentations for 110 (79.4%) individuals; Streptococcus pneumoniae and Haemophilus influenzae were the most common (each identified in 58% of episodes). The overall sensitivity for any bacterium detected in mailed specimens was 82.2% (95% CI 73.6, 88.1) compared to 94.8% (95% CI 89.4, 98.1) for frozen specimens. The sensitivity of the two methods varied by species identified. Conclusion The mailing of unfrozen nasal specimens from remote communities appears to influence the utility of the specimen for bacterial studies, with a loss in sensitivity for the detection of any species overall. Further studies are needed to confirm our finding and to investigate the possible mechanisms of effect. Clinical trial registration Australia and New Zealand Clinical Trials Registry Number: ACTRN12609001006235. Keywords: Respiratory bacteria; RT-PCR; Specimen transport; Laboratory methods

Using a Bayesian network to model colonisation with Vancomycin Resistant Enterococcus (VRE)

Objective: Effective management of multi-resistant organisms is an important issue for hospitals both in Australia and overseas. This study investigates the utility of using Bayesian Network (BN) analysis to examine relationships between risk factors and colonization with Vancomycin Resistant Enterococcus (VRE). Design: Bayesian Network Analysis was performed using infection control data collected over a period of 36 months (2008-2010). Setting: Princess Alexandra Hospital (PAH), Brisbane. Outcome of interest: Number of new VRE Isolates Methods: A BN is a probabilistic graphical model that represents a set of random variables and their conditional dependencies via a directed acyclic graph (DAG). BN enables multiple interacting agents to be studied simultaneously. The initial BN model was constructed based on the infectious disease physician‟s expert knowledge and current literature. Continuous variables were dichotomised by using third quartile values of year 2008 data. BN was used to examine the probabilistic relationships between VRE isolates and risk factors; and to establish which factors were associated with an increased probability of a high number of VRE isolates. Software: Netica (version 4.16). Results: Preliminary analysis revealed that VRE transmission and VRE prevalence were the most influential factors in predicting a high number of VRE isolates. Interestingly, several factors (hand hygiene and cleaning) known through literature to be associated with VRE prevalence, did not appear to be as influential as expected in this BN model. Conclusions: This preliminary work has shown that Bayesian Network Analysis is a useful tool in examining clinical infection prevention issues, where there is often a web of factors that influence outcomes. This BN model can be restructured easily enabling various combinations of agents to be studied.

Most relevant strategies for preventing surgical site infection after total hip arthroplasty : guideline recommendations and expert opinion

BACKGROUND: Numerous strategies are available to prevent surgical site infections in hip arthroplasty, but there is no consensus on which might be the best. This study examined infection prevention strategies currently recommended for patients undergoing hip arthroplasty. METHODS: Four clinical guidelines on infection prevention/orthopedics were reviewed. Infection control practitioners, infectious disease physicians, and orthopedic surgeons were consulted through structured interviews and an online survey. Strategies were classified as "highly important" if they were recommended by at least one guideline and ranked as significantly or critically important by >/=75% of the experts. RESULTS: The guideline review yielded 28 infection prevention measures, with 7 identified by experts as being highly important in this context: antibiotic prophylaxis, antiseptic skin preparation of patients, hand/forearm antisepsis by surgical staff, sterile gowns/surgical attire, ultraclean/laminar air operating theatres, antibiotic-impregnated cement, and surveillance. Controversial measures included antibiotic-impregnated cement and, considering recent literature, laminar air operating theatres. CONCLUSIONS: Some of these measures may already be accepted as routine clinical practice, whereas others are controversial. Whether these practices should be continued for this patient group will be informed by modeling the cost-effectiveness of infection prevention strategies. This will allow predictions of long-term health and cost outcomes and thus inform decisions on how to best use scarce health care resources for infection control.

The development of an effective vaccine against Chlamydia : utilisation of a non-toxic mucosal adjuvant to generate a protective mucosal response

Chlamydia is responsible for a wide range of diseases with enormous global economic and health burden. As the majority of chlamydial infections are asymptomatic, a vaccine has greatest potential to reduce infection and disease prevalence. Protective immunity against Chlamydia requires the induction of a mucosal immune response, ideally, at the multiple sites in the body where an infection can be established. Mucosal immunity is most effectively stimulated by targeting vaccination to the epithelium, which is best accomplished by direct vaccine application to mucosal surfaces rather than by injection. The efficacy of needle-free vaccines however is reliant on a powerful adjuvant to overcome mucosal tolerance. As very few adjuvants have proven able to elicit mucosal immunity without harmful side effects, there is a need to develop non-toxic adjuvants or safer ways to administered pre-existing toxic adjuvants. In the present study we investigated the novel non-toxic mucosal adjuvant CTA1-DD. The immunogenicity of CTA1-DD was compared to our "gold-standard" mucosal adjuvant combination of cholera toxin (CT) and cytosine-phosphate-guanosine oligodeoxynucleotide (CpG-ODN). We also utilised different needle-free immunisation routes, intranasal (IN), sublingual (SL) and transcutaneous (TC), to stimulate the induction of immunity at multiple mucosal surfaces in the body where Chlamydia are known to infect. Moreover, administering each adjuvant by different routes may also limit the toxicity of the CT/CpG adjuvant, currently restricted from use in humans. Mice were immunised with either adjuvant together with the chlamydial major outer membrane protein (MOMP) to evaluate vaccine safety and quantify the induction of antigen-specific mucosal immune responses. The level of protection against infection and disease was also assessed in vaccinated animals following a live genital or respiratory tract infectious challenge. The non-toxic CTA1-DD was found to be safe and immunogenic when delivered via the IN route in mice, inducing a comparable mucosal response and level of protective immunity against chlamydial challenge to its toxic CT/CpG counterpart administered by the same route. The utilisation of different routes of immunisation strongly influenced the distribution of antigen-specific responses to distant mucosal surfaces and also abrogated the toxicity of CT/CpG. The CT/CpG-adjuvanted vaccine was safe when administered by the SL and TC routes and conferred partial immunity against infection and pathology in both challenge models. This protection was attributed to the induction of antigen-specific pro-inflammatory cellular responses in the lymph nodes regional to the site of infection and rather than in the spleen. Development of non-toxic adjuvants and effective ways to reduce the side effects of toxic adjuvants has profound implications for vaccine development, particularly against mucosal pathogens like Chlamydia. Interestingly, we also identified two contrasting vaccines in both infection models capable of preventing infection or pathology exclusively. This indicated that the development of pathology following an infection of vaccinated animals was independent of bacterial load and was instead the result of immunopathology, potentially driven by the adaptive immune response generated following immunisation. While both vaccines expressed high levels of interleukin (IL)-17 cytokines, the pathology protected group displayed significantly reduced expression of corresponding IL-17 receptors and hence an inhibition of signalling. This indicated that the balance of IL-17-mediated responses defines the degree of protection against infection and tissue damage generated following vaccination. This study has enabled us to better understand the immune basis of pathology and protection, necessary to design more effective vaccines.

Repeated intrauterine exposures to inflammatory stimuli attenuated transforming growth factor-β signaling in the ovine fetal lung

Background: Bronchopulmonary dysplasia (BPD) is one of the most common complications after preterm birth and is associated with intrauterine exposure to bacteria. Transforming growth factor-β (TGFβ) is implicated in the development of BPD. Objectives: We hypothesized that different and/or multiple bacterial signals could elicit divergent TGFβ signaling responses in the developing lung. Methods: Time-mated pregnant Merino ewes received an intra-amniotic injection of lipopolysaccharide (LPS) and/or Ureaplasma parvum serovar 3 (UP) at 117 days' and/or 121/122 days' gestational age (GA). Controls received an equivalent injection of saline and or media. Lambs were euthanized at 124 days' GA (term = 150 days' GA). TGFβ1, TGFβ2, TGFβ3, TGFβ receptor (R)1 and TGFβR2 protein levels, Smad2 phosphorylation and elastin deposition were evaluated in lung tissue. Results: Total TGFβ1 and TGFβ2 decreased by 24 and 51% after combined UP+LPS exposure, whereas total TGFβ1 increased by 31% after 7 days' LPS exposure but not after double exposures. Alveolar expression of TGFβR2 decreased 75% after UP, but remained unaltered after double exposures. Decreased focal elastin deposition after single LPS exposure was prevented by double exposures. Conclusions: TGFβ signaling components and elastin responded differently to intrauterine LPS and UP exposure. Multiple bacterial exposures attenuated TGFβ signaling and normalized elastin deposition.

Secured e-health data retrieval in DaaS and Big Data

Big Data is a rising IT trend similar to cloud computing, social networking or ubiquitous computing. Big Data can offer beneficial scenarios in the e-health arena. However, one of the scenarios can be that Big Data needs to be kept secured for a long period of time in order to gain its benefits such as finding cures for infectious diseases and protecting patient privacy. From this connection, it is beneficial to analyse Big Data to make meaningful information while the data is stored securely. Therefore, the analysis of various database encryption techniques is essential. In this study, we simulated 3 types of technical environments, namely, Plain-text, Microsoft Built-in Encryption, and custom Advanced Encryption Standard, using Bucket Index in Data-as-a-Service. The results showed that custom AES-DaaS has a faster range query response time than MS built-in encryption. Furthermore, while carrying out the scalability test, we acknowledged that there are performance thresholds depending on physical IT resources. Therefore, for the purpose of efficient Big Data management in eHealth it is noteworthy to examine their scalability limits as well even if it is under a cloud computing environment. In addition, when designing an e-health database, both patient privacy and system performance needs to be dealt as top priorities.

A systematic review of mathematical models of mosquito-borne pathogen transmission: 1970-2010

Mathematical models of mosquito-borne pathogen transmission originated in the early twentieth century to provide insights into how to most effectively combat malaria. The foundations of the Ross–Macdonald theory were established by 1970. Since then, there has been a growing interest in reducing the public health burden of mosquito-borne pathogens and an expanding use of models to guide their control. To assess how theory has changed to confront evolving public health challenges, we compiled a bibliography of 325 publications from 1970 through 2010 that included at least one mathematical model of mosquito-borne pathogen transmission and then used a 79-part questionnaire to classify each of 388 associated models according to its biological assumptions. As a composite measure to interpret the multidimensional results of our survey, we assigned a numerical value to each model that measured its similarity to 15 core assumptions of the Ross–Macdonald model. Although the analysis illustrated a growing acknowledgement of geographical, ecological and epidemiological complexities in modelling transmission, most models during the past 40 years closely resemble the Ross–Macdonald model. Modern theory would benefit from an expansion around the concepts of heterogeneous mosquito biting, poorly mixed mosquito-host encounters, spatial heterogeneity and temporal variation in the transmission process.

Transcription and expression of Plasmodium falciparum histidine-rich proteins in different stages and strains : implications for rapid diagnostic tests

Background: Although rapid diagnostic tests (RDTs) for Plasmodium falciparum infection that target histidine rich protein 2 (PfHRP2) are generally sensitive, their performance has been reported to be variable. One possible explanation for variable test performance is differences in expression level of PfHRP in different parasite isolates. Methods: Total RNA and protein were extracted from synchronised cultures of 7 P. falciparum lines over 5 time points of the life cycle, and from synchronised ring stages of 10 falciparum lines. Using quantitative real-time polymerase chain reaction, Western blot analysis and ELISA we investigated variations in the transcription and protein levels of pfhrp2, pfhrp3 and PfHRP respectively in the different parasite lines, over the parasite intraerythrocytic life cycle. Results: Transcription of pfhrp2 and pfhrp3 in different parasite lines over the parasite life cycle was observed to vary relative to the control parasite K1. In some parasite lines very low transcription of these genes was observed. The peak transcription was observed in ring-stage parasites. Pfhrp2 transcription was observed to be consistently higher than pfhrp3 transcription within parasite lines. The intraerythrocytic lifecycle stage at which the peak level of protein was present varied across strains. Total protein levels were more constant relative to total mRNA transcription, however a maximum 24 fold difference in expression at ring-stage parasites relative to the K1 strain was observed. Conclusions: The levels of transcription of pfhrp2 and pfhrp3, and protein expression of PfHRP varied between different P. falciparum strains. This variation may impact on the detection sensitivity of PfHRP2-detecting RDTs.

Sunshine, rainfall, humidity and child pneumonia in the tropics : time-series analyses

Few studies have formally examined the relationship between meteorological factors and the incidence of child pneumonia in the tropics, despite the fact that most child pneumonia deaths occur there. We examined the association between four meteorological exposures (rainy days, sunshine, relative humidity, temperature) and the incidence of clinical pneumonia in young children in the Philippines using three time-series methods: correlation of seasonal patterns, distributed lag regression, and case-crossover. Lack of sunshine was most strongly associated with pneumonia in both lagged regression [overall relative risk over the following 60 days for a 1-h increase in sunshine per day was 0·67 (95% confidence interval (CI) 0·51–0·87)] and case-crossover analysis [odds ratio for a 1-h increase in mean daily sunshine 8–14 days earlier was 0·95 (95% CI 0·91–1·00)]. This association is well known in temperate settings but has not been noted previously in the tropics. Further research to assess causality is needed.

Antibiotic resistance and virulence traits in clinical and environmental Enterococcus faecalis and Enterococcus faecium isolates

This study compared virulence and antibiotic resistance traits in clinical and environmental E. faecalis and E. faecium isolates. E. faecalis isolates harboured a broader spectrum of virulence determinants compared to E. faecium isolates. The virulence traits Cyl-A, Cyl-B, Cyl-M, gel-E and esp were tested and environmental isolates predominantly harboured gel-E (80% of E. faecalis and 31.9% of E. faecium) whereas esp was more prevalent in clinical isolates (67.79% of E. faecalis and 70.37 % of E. faecium). E. faecalis and E. faecium isolated from water had different antibiotic resistance patterns compared to those isolated from clinical samples. Linozolid resistance was not observed in any isolates tested and vancomycin resistance was observed only in clinical isolates. Resistance to other antibiotics (tetracycline, gentamicin, ciprofloxacin and ampicillin) was detected in both clinical and water isolates. Clinical isolates were more resistant to all the antibiotics tested compared to water isolates. Multi-drug resistance was more prevalent in clinical isolates (71.18% of E. faecalis and 70.3 % of E. faecium) compared to water isolates (only 5.66 % E. faecium). tet L and tet M genes were predominantly identified in tetracycline-resistant isolates. All water and clinical isolates resistant to ciprofloxacin and ampicillin contained mutations in the gyrA, parC and pbp5 genes. A significant correlation was found between the presence of virulence determinants and antibiotic resistance in all the isolates tested in this study (p<0.05). The presence of antibiotic resistant enterococci, together with associated virulence traits, in surface recreational water could be a public health risk.