Transcutaneous immunization with combined cholera toxin and CpG adjuvant protects against Chlamydia muridarum genital tract infection

Chlamydia trachomatis is a pathogen of the genital tract and ocular epithelium. Infection is established by the binding of the metabolically inert elementary body (EB) to epithelial cells. These are taken up by endocytosis into a membrane-bound vesicle termed an inclusion. The inclusion avoids fusion with host lysosomes, and the EBs differentiate into the metabolically active reticulate body (RB), which replicates by binary fission within the protected environment of the inclusion. During the extracellular EB stage of the C. trachomatis life cycle, antibody present in genital tract or ocular secretions can inhibit infection both in vivo and in tissue culture. The RB, residing within the intracellular inclusion, is not accessible to antibody, and resolution of infection at this stage requires a cell-mediated immune response mediated by gamma interferon-secreting Th1 cells. Thus, an ideal vaccine to protect against C. trachomatis genital tract infection should induce both antibody (immunoglobulin A [IgA] and IgG) responses in mucosal secretions to prevent infection by chlamydial EB and a strong Th1 response to limit ascending infection to the uterus and fallopian tubes. In the present study we show that transcutaneous immunization with major outer membrane protein (MOMP) in combination with both cholera toxin and CpG oligodeoxynucleotides elicits MOMP-specific IgG and IgA in vaginal and uterine lavage fluid, MOMP-specific IgG in serum, and gamma interferon-secreting T cells in reproductive tract-draining caudal and lumbar lymph nodes. This immunization protocol resulted in enhanced clearance of C. muridarum (C. trachomatis, mouse pneumonitis strain) following intravaginal challenge of BALB/c mice.

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.

The mouse model of Chlamydia genital tract infection: a review of infection, disease, immunity and vaccine development

Chlamydia trachomatis is the most common sexually transmitted bacterial infection worldwide. The impact of this pathogen on human reproduction has intensified research efforts to better understand chlamydial infection and pathogenesis. Whilst there are animal models available that mimic the many aspects of human chlamydial infection, the mouse is regarded as the most practical and widely used of the models. Studies in mice have greatly contributed to our understanding of the host-pathogen interaction and provided an excellent medium for evaluating vaccines. Here we explore the advantages and disadvantages of all animal models of chlamydial genital tract infection, with a focus on the murine model and what we have learnt from it so far.

Co-morbidity of depression and anxiety in common age-related eye diseases : a population-based study of 662 adults

This study examined the prevalence of co-morbid age-related eye disease and symptoms of depression and anxiety in late life, and the relative roles of visual function and disease in explaining symptoms of depression and anxiety. A community-based sample of 662 individuals aged over 70 years was recruited through the electoral roll. Vision was measured using a battery of tests including high and low contrast visual acuity, contrast sensitivity, motion sensitivity, stereoacuity, Useful Field of View, and visual fields. Depression and anxiety symptoms were measured using the Goldberg scales. The prevalence of self-reported eye disease [cataract, glaucoma, or age-related macular degeneration (AMD)] in the sample was 43.4%, with 7.7% reporting more than one form of ocular pathology. Of those with no eye disease, 3.7% had clinically significant depressive symptoms. This rate was 6.7% among cataract patients, 4.3% among those with glaucoma, and 10.5% for AMD. Generalized linear models adjusting for demographics, general health, treatment, and disability examined self-reported eye disease and visual function as correlates of depression and anxiety. Depressive symptoms were associated with cataract only, AMD, comorbid eye diseases and reduced low contrast visual acuity. Anxiety was significantly associated with self-reported cataract, and reduced low contrast visual acuity, motion sensitivity and contrast sensitivity. We found no evidence for elevated rates of depressive or anxiety symptoms associated with self-reported glaucoma. The results support previous findings of high rates of depression and anxiety in cataract and AMD, and in addition show that mood and anxiety are associated with objective measures of visual function independently of self-reported eye disease. The findings have implications for the assessment and treatment of mental health in the context of late-life visual impairment...

The impact of heat waves on children's health : a systematic review

Young children are thought to be particularly sensitive to heatwaves, but relatively less research attention has been paid to this field to date. A systematic review was conducted to elucidate the relationship between heat waves and children’s health. Literature published up to August 2012 were identified using the following MeSH terms and keywords: “heatwave”, “heat wave”, “child health”, “morbidity”, “hospital admission”, “emergency department visit”, “family practice”, “primary health care”, “death” and “mortality”. Of the 628 publications identified, 12 met the selection criteria. The existing literature does not consistently suggest that mortality among children increases significantly during heat waves, even though infants were associated with more heat-related deaths. Exposure to heat waves in the perinatal period may pose a threat to children’s health. Pediatric diseases or conditions associated with heat waves include renal disease, respiratory disease, electrolyte imbalance and fever. Future research should focus on how to develop a consistent definition of a heat wave from a children’s health perspective, identifying the best measure of children’s exposure to heat waves, exploring sensitive outcome measures to quantify the impact of heat waves on children, evaluating the possible impacts of heat waves on children’s birth outcomes, and understanding the differences in vulnerability to heat waves among children of different ages and from different income countries. Projection of the children’s disease burden caused by heat waves under climate change scenarios, and development of effective heat wave mitigation and adaptation strategies that incorporate other child protective health measures, are also strongly recommended.

Extreme temperatures and paediatric emergency department admissions

Background Children are particularly vulnerable to the effects of extreme temperatures. Objective To examine the relationship between extreme temperatures and paediatric emergency department admissions (EDAs) in Brisbane, Australia, during 2003–2009. Methods A quasi-Poisson generalised linear model combined with a distributed lag non-linear model was used to examine the relationships between extreme temperatures and age-, gender- and cause-specific paediatric EDAs, while controlling for air pollution, relative humidity, day of the week, influenza epidemics, public holiday, season and long-term trends. The model residuals were checked to identify whether there was an added effect due to heat waves or cold spells. Results There were 131 249 EDAs among children during the study period. Both high (RR=1.27; 95% CI 1.12 to 1.44) and low (RR=1.81; 95% CI 1.66 to 1.97) temperatures were significantly associated with an increase in paediatric EDAs in Brisbane. Male children were more vulnerable to temperature effects. Children aged 0–4 years were more vulnerable to heat effects and children aged 10–14 years were more sensitive to both hot and cold effects. High temperatures had a significant impact on several paediatric diseases, including intestinal infectious diseases, respiratory diseases, endocrine, nutritional and metabolic diseases, nervous system diseases and chronic lower respiratory diseases. Low temperatures were significantly associated with intestinal infectious diseases, respiratory diseases and endocrine, nutritional and metabolic diseases. An added effect of heat waves on childhood chronic lower respiratory diseases was seen, but no added effect of cold spells was found. Conclusions As climate change continues, children are at particular risk of a variety of diseases which might be triggered by extremely high temperatures. This study suggests that preventing the effects of extreme temperature on children with respiratory diseases might reduce the number of EDAs.

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.

Impact of ambient temperature on children's health : a systematic review

Children are vulnerable to temperature extremes. This paper aimed to review the literature regarding the relationship between ambient temperature and children’s health and to propose future research directions. A literature search was conducted in February 2012 using the databases including PubMed, ProQuest, ScienceDirect, Scopus and Web of Science. Empirical studies regarding the impact of ambient temperature on children’s mortality and morbidity were included. The existing literature indicates that very young children, especially children under one year of age, are particularly vulnerable to heat-related deaths. Hot and cold temperatures mainly affect cases of infectious diseases among children, including gastrointestinal diseases, malaria, hand, foot and mouse disease, and respiratory diseases. Paediatric allergic diseases, like eczema, are also sensitive to temperature extremes. During heat waves, the incidences of renal disease, fever and electrolyte imbalance among children increase significantly. Future research is needed to examine the balance between hot- and cold-temperature related mortality and morbidity among children; evaluate the impacts of cold spells on cause-specific mortality in children; identify the most sensitive temperature exposure and health outcomes to quantify the impact of temperature extremes on children; elucidate the possible modifiers of the temperature and children’s health relationship; and project children’s disease burden under different climate change scenarios.

Climate change and children’s health : a call for research on what works to protect children

Climate change is affecting and will increasingly influence human health and wellbeing. Children are particularly vulnerable to the impact of climate change. An extensive literature review regarding the impact of climate change on children’s health was conducted in April 2012 by searching electronic databases PubMed, Scopus, ProQuest, ScienceDirect, and Web of Science, as well as relevant websites, such as IPCC and WHO. Climate change affects children’s health through increased air pollution, more weather-related disasters, more frequent and intense heat waves, decreased water quality and quantity, food shortage and greater exposure to toxicants. As a result, children experience greater risk of mental disorders, malnutrition, infectious diseases, allergic diseases and respiratory diseases. Mitigation measures like reducing carbon pollution emissions, and adaptation measures such as early warning systems and post-disaster counseling are strongly needed. Future health research directions should focus on: (1) identifying whether climate change impacts on children will be modified by gender, age and socioeconomic status; (2) refining outcome measures of children’s vulnerability to climate change; (3) projecting children’s disease burden under climate change scenarios; (4) exploring children’s disease burden related to climate change in low-income countries, and ; (5) identifying the most cost-effective mitigation and adaptation actions from a children’s health perspective.

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.

Tailored interventions based on sputum eosinophils versus clinical symptoms for asthma in children and adults

BACKGROUND Asthma severity and control can be measured both subjectively and objectively. Sputum analysis for evaluation of percentage of sputum eosinophilia directly measures airway inflammation, and is one method of objectively monitoring asthma. Interventions for asthma therapies have been traditionally based on symptoms and spirometry. OBJECTIVES To evaluate the efficacy of tailoring asthma interventions based on sputum analysis in comparison to clinical symptoms (with or without spirometry/peak flow) for asthma related outcomes in children and adults. SEARCH STRATEGY We searched the Cochrane Airways Group Specialised Register of Trials, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and reference lists of articles. The last search was on 31 October 2006. SELECTION CRITERIA All randomised controlled comparisons of adjustment of asthma therapy based on sputum eosinophils compared to traditional methods (primarily clinical symptoms and spirometry/peak flow). DATA COLLECTION AND ANALYSIS Results of searches were reviewed against pre-determined criteria for inclusion. Three sets of reviewers selected relevant studies.Two review authors independently assessed trial quality extracted data. Authors were contacted for further information but none were received. Data was analysed as "treatment received" and sensitivity analyses performed. MAIN RESULTS Three adult studies were included; these studies were clinically and methodologically heterogenous (use of medications, cut off for percentage of sputum eosinophils and definition of asthma exacerbation). There were no eligible paediatric studies. Of 246 participants randomised, 221 completed the trials. In the meta-analysis, a significant reduction in number of participants who had one or more asthma exacerbations occurred when treatment was based on sputum eosinophils in comparison to clinical symptoms; pooled odds ratio (OR) was 0.49 (95% CI 0.28 to 0.87); number needed to treat to benefit (NNTB) was 6 (95% CI 4 to 32).There were also differences between groups in the rate of exacerbation (any exacerbation per year) and severity of exacerbations defined by requirement for use of oral corticosteroids but the reduction in hospitalisations was not statistically significant. Data for clinical symptoms, quality of life and spirometry were not significantly different between groups. The mean dose of inhaled corticosteroids per day was similar in both groups and no adverse events were reported. However sputum induction was not always possible. AUTHORS' CONCLUSIONS Tailored asthma interventions based on sputum eosinophils is beneficial in reducing the frequency of asthma exacerbations in adults with asthma. This review supports the use of sputum eosinophils to tailor asthma therapy for adults with frequent exacerbations and severe asthma. Further studies need to be undertaken to strengthen these results and no conclusion can be drawn for children with asthma.

The impact of viral respiratory infection on the severity and recovery from an asthma exacerbation

Background Viral respiratory illness triggers asthma exacerbations, but the influence of respiratory illness on the acute severity and recovery of childhood asthma is unknown. Our objective was to evaluate the impact of a concurrent acute respiratory illness (based on a clinical definition and PCR detection of a panel of respiratory viruses, Mycoplasma pneumoniae and Chlamydia pneumoniae) on the severity and resolution of symptoms in children with a nonhospitalized exacerbation of asthma. Methods Subjects were children aged 2 to 15 years presenting to an emergency department for an acute asthma exacerbation and not hospitalized. Acute respiratory illness (ARI) was clinically defined. Nasopharyngeal aspirates (NPA) were examined for respiratory viruses, Chlamydia and Mycoplasma using PCR. The primary outcome was quality of life (QOL) on presentation, day 7 and day 14. Secondary outcomes were acute asthma severity score, asthma diary, and cough diary scores on days 5, 7,10, and 14. Results On multivariate regression, presence of ARI was statistically but not clinically significantly associated with QOL score on presentation (B = 0.36, P = 0.025). By day 7 and 14, there was no difference between groups. Asthma diary score was significantly higher in children with ARI (B = 0.41, P = 0.039) on day 5 but not on presentation or subsequent days. Respiratory viruses were detected in 54% of the 78 NPAs obtained. There was no difference in the any of the asthma outcomes of children grouped by positive or negative NPA. Conclusions The presence of a viral respiratory illness has a modest influence on asthma severity, and does not influence recovery from a nonhospitalized asthma exacerbation.

A 5- versus 3-day course of oral corticosteroids for children with asthma exacerbations who are not hospitalised : a randomised controlled trial

Objective To determine whether a 5-day course of oral prednisolone is superior to a 3-day course in reducing the 2-week morbidity of children with asthma exacerbations who are not hospitalised. Design, setting and participants Double-blind randomised controlled trial of asthma outcomes following a 5-day course of oral prednisolone (1 mg/kg) compared with a 3-day course of prednisolone plus placebo for 2 days. Participants were children aged 2–15 years who presented to the emergency departments of three Queensland hospitals between March 2004 and February 2007 with an acute exacerbation of asthma, but were not hospitalised. Sample size was defined a priori for a study power of 90%. Main outcome measures Difference in proportion of children who were symptom-free at Day 7, as measured by intention-to-treat (ITT) and per-protocol analysis; quality of life (QOL) on Days 7 and 14. Results 201 children were enrolled, and there was an 82% completion rate. There was no difference between groups in the proportion of children who were symptom-free (observed difference, 0.04 [95% CI, − 0.09 to 0.18] by ITT analysis; 0.04 [95% CI, − 0.17 to 0.09] by per-protocol analysis). There was also no difference between groups in QOL (P = 0.42). The difference between groups for the primary outcome was within the equivalence range calculated post priori. Conclusion A 5-day course of oral prednisolone confers no advantage over a 3-day course for children with asthma exacerbations who are not hospitalised.