Carrot red leaf and carrot mottle viruses : observations on the composition of the particles in single and mixed infections

Particles of carrot red leaf virus (CRLV; luteovirus group) purified from chervil (Anthriscus cerefolium) contain a single ssRNA species of mol. wt. about 1.8 x 106 and a major protein of mol. wt. about 25000. CRLV acts as a helper for aphid transmission of carrot mottle virus (CMotV; ungrouped) from mixedly infected plants. Virus preparations purified from such plants possess the infectivity of both viruses but contain particles indistinguishable from those of CRLV; some of the particles are therefore thought to consist of CMotV RNA packaged in CRLV coat protein. When RNA from such preparations was electrophoresed in agarose/polyacrylamide gels, CMotV infectivity was associated with an RNA band that migrated ahead of the CRLV RNA band and had an estimated mol. wt. of about 1.5 x 106, similar to that previously found for the infective ssRNA extracted directly from Nicotiana clevelandii leaves infected with CMotV alone. Preparations of dsRNA from CMotV-infected N. clevelandii leaves contained two species: one of mol. wt. about 3.2 x 106, presumably the replicative form of the infective ssRNA, and the other, mol. wt. about 0.9 x 106, of unknown origin and function. The infective agent in buffer extracts of CMotV-infected N. clevelandii was resistant to RNase (although the enzyme acted as a reversible inhibitor of infection at high concentrations) and is therefore not unprotected RNA. It may be protected within the approximately 52 nm enveloped structures previously reported.

Innate and adaptive immunity at mucosal surfaces of the female reproductive tract : stratification and integration of immune protection against the transmission of sexually transmitted infections

This review examines the multiple levels of pre-existing immunity in the upper and lower female reproductive tract. In addition, we highlight the need for further research of innate and adaptive immune protection of mucosal surfaces in the female reproductive tract. Innate mechanisms include the mucus lining, a tight epithelial barrier and the secretion of antimicrobial peptides and cytokines by epithelial and innate immune cells. Stimulation of the innate immune system also serves to bridge the adaptive arm resulting in the generation of pathogen-specific humoral and cell-mediated immunity. Less understood are the multiple components that act in a coordinated way to provide a network of ongoing protection. Innate and adaptive immunity in the human female reproductive tract are influenced by the stage of menstrual cycle and are directly regulated by the sex steroid hormones, progesterone and estradiol. Furthermore, the effect of hormones on immunity is mediated both directly on immune and epithelial cells and indirectly by stimulating growth factor secretion from stromal cells. The goal of this review is to focus on the diverse aspects of the innate and adaptive immune systems that contribute to a unique network of protection throughout the female reproductive tract.

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 …

Long-term azithromycin for Indigenous children with non-cystic-fibrosis bronchiectasis or chronic suppurative lung disease (Bronchiectasis Intervention Study) : a multicentre, double-blind, randomised controlled trial

Background Indigenous children in high-income countries have a heavy burden of bronchiectasis unrelated to cystic fibrosis. We aimed to establish whether long-term azithromycin reduced pulmonary exacerbations in Indigenous children with non-cystic-fibrosis bronchiectasis or chronic suppurative lung disease. Methods Between Nov 12, 2008, and Dec 23, 2010, we enrolled Indigenous Australian, Maori, and Pacific Island children aged 1—8 years with either bronchiectasis or chronic suppurative lung disease into a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial. Eligible children had had at least one pulmonary exacerbation in the previous 12 months. Children were randomised (1:1 ratio, by computer-generated sequence with permuted block design, stratified by study site and exacerbation frequency [1—2 vs ≥3 episodes in the preceding 12 months]) to receive either azithromycin (30 mg/kg) or placebo once a week for up to 24 months. Allocation concealment was achieved by double-sealed, opaque envelopes; participants, caregivers, and study personnel were masked to assignment until after data analysis. The primary outcome was exacerbation (respiratory episodes treated with antibiotics) rate. Analysis of the primary endpoint was by intention to treat. At enrolment and at their final clinic visits, children had deep nasal swabs collected, which we analysed for antibiotic-resistant bacteria. This study is registered with the Australian New Zealand Clinical Trials Registry; ACTRN12610000383066. Findings 45 children were assigned to azithromycin and 44 to placebo. The study was stopped early for feasibility reasons on Dec 31, 2011, thus children received the intervention for 12—24 months. The mean treatment duration was 20·7 months (SD 5·7), with a total of 902 child-months in the azithromycin group and 875 child-months in the placebo group. Compared with the placebo group, children receiving azithromycin had significantly lower exacerbation rates (incidence rate ratio 0·50; 95% CI 0·35—0·71; p<0·0001). However, children in the azithromycin group developed significantly higher carriage of azithromycin-resistant bacteria (19 of 41, 46%) than those receiving placebo (four of 37, 11%; p=0·002). The most common adverse events were non-pulmonary infections (71 of 112 events in the azithromycin group vs 132 of 209 events in the placebo group) and bronchiectasis-related events (episodes or investigations; 22 of 112 events in the azithromycin group vs 48 of 209 events in the placebo group); however, study drugs were well tolerated with no serious adverse events being attributed to the intervention. Interpretation Once-weekly azithromycin for up to 24 months decreased pulmonary exacerbations in Indigenous children with non-cystic-fibrosis bronchiectasis or chronic suppurative lung disease. However, this strategy was also accompanied by increased carriage of azithromycin-resistant bacteria, the clinical consequences of which are uncertain, and will need careful monitoring and further study.

Immunization with a MOMP-based vaccine protects mice against a Pulmonary Chlamydia challenge and identifies a disconnection between infection and pathology

Chlamydia pneumoniae is responsible for up to 20% of community acquired pneumonia and can exacerbate chronic inflammatory diseases. As the majority of infections are either mild or asymptomatic, a vaccine is recognized to have the greatest potential to reduce infection and disease prevalence. Using the C. muridarum mouse model of infection, we immunized animals via the intranasal (IN), sublingual (SL) or transcutaneous (TC) routes, with recombinant chlamydial major outer membrane protein (MOMP) combined with adjuvants CTA1-DD or a combination of cholera toxin/CpG-oligodeoxynucleotide (CT/CpG). Vaccinated animals were challenged IN with C. muridarum and protection against infection and pathology was assessed. SL and TC immunization with MOMP and CT/CpG was the most protective, significantly reducing chlamydial burden in the lungs and preventing weight loss, which was similar to the protection induced by a previous live infection. Unlike a previous infection however, these vaccinations also provided almost complete protection against fibrotic scarring in the lungs. Protection against infection was associated with antigen-specific production of IFNγ, TNFα and IL-17 by splenocytes, however, protection against both infection and pathology required the induction of a similar pro-inflammatory response in the respiratory tract draining lymph nodes. Interestingly, we also identified two contrasting vaccinations capable of preventing infection or pathology individually. Animals IN immunized with MOMP and either adjuvant were protected from infection, but not the pathology. Conversely, animals TC immunized with MOMP and CTA1-DD were protected from pathology, even though the chlamydial burden in this group was equivalent to the unimmunized controls. This suggests that the development of pathology following an IN infection of vaccinated animals was independent of bacterial load and may have been driven instead by the adaptive immune response generated following immunization. This identifies a disconnection between the control of infection and the development of pathology, which may influence the design of future vaccines.

Multilocus sequence analysis provides insights into molecular epidemiology of Chlamydia pecorum infections in Australian sheep, cattle and koalas

Chlamydia pecorum is a significant pathogen of domestic livestock and wildlife. We have developed a C. pecorum-specific multilocus sequence analysis (MLSA) scheme to examine the genetic diversity of and relationships between Australian sheep, cattle, and koala isolates. An MLSA of seven concatenated housekeeping gene fragments was performed using 35 isolates, including 18 livestock isolates (11 Australian sheep, one Australian cow, and six U.S. livestock isolates) and 17 Australian koala isolates. Phylogenetic analyses showed that the koala isolates formed a distinct clade, with limited clustering with C. pecorum isolates from Australian sheep. We identified 11 MLSA sequence types (STs) among Australian C. pecorum isolates, 10 of them novel, with koala and sheep sharing at least one identical ST (designated ST2013Aa). ST23, previously identified in global C. pecorum livestock isolates, was observed here in a subset of Australian bovine and sheep isolates. Most notably, ST23 was found in association with multiple disease states and hosts, providing insights into the transmission of this pathogen between livestock hosts. The complexity of the epidemiology of this disease was further highlighted by the observation that at least two examples of sheep were infected with different C. pecorum STs in the eyes and gastrointestinal tract. We have demonstrated the feasibility of our MLSA scheme for understanding the host relationship that exists between Australian C. pecorum strains and provide the first molecular epidemiological data on infections in Australian livestock hosts.

Control strategies to prevent total hip replacement-related infections : a systematic review and mixed treatment comparison

OBJECTIVE: To synthesise the available evidence and estimate the comparative efficacy of control strategies to prevent total hip replacement (THR)-related surgical site infections (SSIs) using a mixed treatment comparison. DESIGN: Systematic review and mixed treatment comparison. SETTING: Hospital and other healthcare settings. PARTICIPANTS: Patients undergoing THR. PRIMARY AND SECONDARY OUTCOME MEASURES: The number of THR-related SSIs occurring following the surgical operation. RESULTS: 12 studies involving 123 788 THRs and 9 infection control strategies were identified. The strategy of 'systemic antibiotics+antibiotic-impregnated cement+conventional ventilation' significantly reduced the risk of THR-related SSI compared with the referent strategy (no systemic antibiotics+plain cement+conventional ventilation), OR 0.13 (95% credible interval (CrI) 0.03-0.35), and had the highest probability (47-64%) and highest median rank of being the most effective strategy. There was some evidence to suggest that 'systemic antibiotics+antibiotic-impregnated cement+laminar airflow' could potentially increase infection risk compared with 'systemic antibiotics+antibiotic-impregnated cement+conventional ventilation', 1.96 (95% CrI 0.52-5.37). There was no high-quality evidence that antibiotic-impregnated cement without systemic antibiotic prophylaxis was effective in reducing infection compared with plain cement with systemic antibiotics, 1.28 (95% CrI 0.38-3.38). CONCLUSIONS: We found no convincing evidence in favour of the use of laminar airflow over conventional ventilation for prevention of THR-related SSIs, yet laminar airflow is costly and widely used. Antibiotic-impregnated cement without systemic antibiotics may not be effective in reducing THR-related SSIs. The combination with the highest confidence for reducing SSIs was 'systemic antibiotics+antibiotic-impregnated cement+conventional ventilation'. Our evidence synthesis underscores the need to review current guidelines based on the available evidence, and to conduct further high-quality double-blind randomised controlled trials to better inform the current clinical guidelines and practice for prevention of THR-related SSIs.

Prevalence of undiagnosed urinary tract infections on admission to a rehabilitation unit

Background Through clinical observation nursing staff of an inpatient rehabilitation unit identified a link between incontinence and undiagnosed urinary tract infections (UTIs). Further, clinical observation and structured continence management led to the realisation that urinary incontinence often improved, or resolved completely, after treatment with antibiotics. In 2009 a small study found that 30% of admitted rehabilitation patients had an undiagnosed UTI, with the majority admitted post-orthopaedic fracture. We suspected that the frequent use of indwelling urinary catheters (IDCs) in the orthopaedic environment may have been a contributing factor. Therefore, a second, more thorough, study was commenced in 2010 and completed in 2011. Aim The aim of this study was to identify what proportion of patients were admitted to one rehabilitation unit with an undiagnosed UTI over a 12-month period. We wanted to identify and highlight the presence of known risk factors associated with UTI and determine whether urinary incontinence was associated with the presence of UTI. Methods Data were collected from every patient that was admitted over a 12-month period (n=140). The majority of patients were over the age of 65 and had an orthopaedic fracture (36.4%) or stroke (27.1%). Mid-stream urine (MSU) samples, routinely collected and sent for culture and sensitivity as part of standard admission procedure, were used by the treating medical officer to detect the presence of UTI. A data collection sheet was developed, reviewed and trialled, before official data collection commenced. Data were collected as part of usual practice and collated by a research assistant. Inferential statistics were used to analyse the data. Results This study found that 25 (17.9%) of the 140 patients admitted to rehabilitation had an undiagnosed UTI, with a statistically significant association between prior presence of an IDC and the diagnosis of UTI. Urinary incontinence improved after the completion of treatment with antibiotics. Results further demonstrated a significant association between the confirmation of a UTI on culture and sensitivity and the absence of symptoms usually associated with UTI, such as burning or stinging on urination. Overall, this study suggests careful monitoring of urinary symptoms in patients admitted to rehabilitation, especially in patients with a prior IDC, is warranted.

Lung recruitment manoeuvres for reducing respiratory morbidity in mechanically ventilated neonates

This is the protocol for a review and there is no abstract. The objectives are as follows: To determine the evidence supporting the use of recruitment manoeuvres in mechanically ventilated neonates and identify the optimal method of lung recruitment. To determine the effects of lung recruitment manoeuvres in neonates receiving ventilatory support on neonatal mortality and development of chronic lung disease when compared to no recruitment. If data are available, subgroup analyses will include: chronological age, gestational age, lung pathophysiology and pre-existing lung disease, mode and length of ventilation, timing and frequency of recruitment techniques.

Heterogeneity of clinical and environmental isolates of Mycobacterium fortuitum using repetitive element sequence-based PCR: municipal water an unlikely source of community-acquired infections

M. fortuitum is a rapidly growing mycobacterium associated with community-acquired and nosocomial wound, soft tissue, and pulmonary infections. It has been postulated that water has been the source of infection especially in the hospital setting. The aim of this study was to determine if municipal water may be the source of community-acquired or nosocomial infections in the Brisbane area. Between 2007 and 2009, 20 strains of M. fortuitum were recovered from municipal water and 53 patients’ isolates were submitted to the reference laboratory. A wide variation in strain types was identified using repetitive element sequence-based PCR, with 13 clusters of ≥2 indistinguishable isolates, and 28 patterns consisting of individual isolates. The clusters could be grouped into seven similar groups (>95% similarity). Municipal water and clinical isolates collected during the same time period and from the same geographical area consisted of different strain types, making municipal water an unlikely source of sporadic human infection.

Assessment of antibiotic use in children by their parents in Saudi Arabia

This project assessed the factors influencing the parents' use of antibiotics in children in Saudi Arabia. It was conducted through the development and validation of the Parental Perceptions on Antibiotics (PAPA) Scales, which is the first valid and reliable instrument directed to measure these factors on a population-based level. This is also the first population-based study that measures the patterns of antibiotic use in children in Saudi Arabia, where a very high association was found between the use of antibiotics and the number of cold episodes a year, which suggests a potential of overuse of antibiotics in Saudi Arabia. Also, it was found that antibiotic use decreases significantly with parents having higher scores in knowledge and beleifs, behaviors, and eagerness to seek health-related information.

STI-GMaS : an open-source environment for simulation of sexually-transmitted infections

Background Sexually-transmitted pathogens often have severe reproductive health implications if treatment is delayed or absent, especially in females. The complex processes of disease progression, namely replication and ascension of the infection through the genital tract, span both extracellular and intracellular physiological scales, and in females can vary over the distinct phases of the menstrual cycle. The complexity of these processes, coupled with the common impossibility of obtaining comprehensive and sequential clinical data from individual human patients, makes mathematical and computational modelling valuable tools in developing our understanding of the infection, with a view to identifying new interventions. While many within-host models of sexually-transmitted infections (STIs) are available in existing literature, these models are difficult to deploy in clinical/experimental settings since simulations often require complex computational approaches. Results We present STI-GMaS (Sexually-Transmitted Infections – Graphical Modelling and Simulation), an environment for simulation of STI models, with a view to stimulating the uptake of these models within the laboratory or clinic. The software currently focuses upon the representative case-study of Chlamydia trachomatis, the most common sexually-transmitted bacterial pathogen of humans. Here, we demonstrate the use of a hybrid PDE–cellular automata model for simulation of a hypothetical Chlamydia vaccination, demonstrating the effect of a vaccine-induced antibody in preventing the infection from ascending to above the cervix. This example illustrates the ease with which existing models can be adapted to describe new studies, and its careful parameterisation within STI-GMaS facilitates future tuning to experimental data as they arise. Conclusions STI-GMaS represents the first software designed explicitly for in-silico simulation of STI models by non-theoreticians, thus presenting a novel route to bridging the gap between computational and clinical/experimental disciplines. With the propensity for model reuse and extension, there is much scope within STI-GMaS to allow clinical and experimental studies to inform model inputs and drive future model development. Many of the modelling paradigms and software design principles deployed to date transfer readily to other STIs, both bacterial and viral; forthcoming releases of STI-GMaS will extend the software to incorporate a more diverse range of infections.

Duty in the time of epidemics : what China and Zimbabwe teach us

In November 2002, a man with ‘atypical pneumonia’ treated in Foshan hospital, Guangdong Province, in the People's Republic of China, was the first known case of Severe Acute Respiratory Syndrome (SARS). However, it was not until April 2003 that the Chinese government admitted to the full scale of ‘atypical pneumonia’ cases infected with SARS, two months after the disease had rapidly spread across the world with initial infections in Hong Kong and Vietnam sourced to Guangdong. In 2008, Zimbabwe experienced one of the biggest outbreaks of cholera ever recorded. By February 2009, the disease had spread across all of Zimbabwe's 10 provinces and to neighbouring countries—Botswana, South Africa, Zambia and Mozambique—causing thousands of infections amongst their populations. This article seeks to examine what duties the Chinese and Zimbabwe states had to protect their citizens and the international community from these outbreaks. The article refers to the findings of the International Law Commission's study into the role of states and international organisations in protecting persons in the event of a disaster to consider whether there is an international duty to protect persons from epidemics. The article concludes that both cases reveal a growing concept of protection that entails an international duty to assist individuals when an affected state proves unwilling or unable to assist its own population in the event of a disease outbreak.

The duty to report disease outbreaks : of interest or value? Lessons from H5N1

Since the severe acute respiratory syndrome outbreak in 2003, it has been argued that there has been a substantial revision to the norm dictating the behaviour of states in the event of a disease outbreak. This article examines the evolution of the norm to ‘report and verify’ disease outbreaks and evaluates the extent to which this revised norm has begun to guide state behaviour. Examination of select East Asian countries affected by human infections of the H5N1 (avian influenza) virus strain reveals the need to further understand the mutually constitutive relationship between the value attached to prompt reporting against the capacity to report, and how states manage both in fulfilling their duty to report.