A comparison of the effects of a chlamydial vaccine administered during or after a C. muridarum urogenital infection of female mice

There are approximately 92 million new chlamydial infections of the genital tract in humans diagnosed each year, costing health care systems billions of dollars in treatment not only of acute infections, but also of associated inflammatory sequelae, such as pelvic inflammatory disease (PID) and ectopic pregnancy. These numbers are increasing at a steady rate and, due to the asymptomatic nature of infections, the incidence may be underestimated and the costs of treatment therefore higher. Over the previous few decades there has been a large amount of research into the development of an efficacious vaccine against genital tract chlamydial infections. The majority of this research has focused on females, due to the high rate of development of associated diseases, including PID, which can lead to ectopic pregnancy and infertility. In light of the increasing infection rates that have occurred despite the availability of antibiotics, and the asymptomatic nature of chlamydial infections, it is imperative that an efficacious vaccine that protects against infection and associated pathology be developed.

Tubal damage, infertility and tubal ectopic pregnancy : chlamydia trachomatis and other microbial aetiologies

Infertility is a worldwide health problem with one in six couples suffering from this condition and with a major economic burden on the global healthcare industry. Estimates of the current global infertility rate suggest that 15% of couples are infertile (Zegers-Hochschild et al 2009) defined as: (1) failure to conceive after 12 months of unprotected sexual intercourse (i.e. infertility); (2) repeated implantation failure following ART cycles; or (3) recurrent miscarriage without difficulty conceiving (natural conceptions). Tubal factor infertility is among the leading causes of female factor infertility accounting for 7-9.8% of all female factor infertilities. Tubal disease directly causes from 36% to 85% of all cases of female factor infertility in developed and developing nations respectively and is associated with polymicrobial aetiologies. One of the leading global causes of tubal factor infertility is thought to be symptomatic (and asymptomatic in up to 70% cases) infection of the female reproductive tract with the sexually transmitted pathogen, Chlamydia trachomatis. Infection-related damage to the Fallopian tubes caused by Chlamydia accounts for more than 70% of cases of infertility in women from developing nations such as sub-Saharan Africa (Sharma et al 2009). Bacterial vaginosis, a condition associated with increased transmission of sexually transmitted infections including those caused by Neisseria gonorrhoeae and Mycoplasma genitalium is present in two thirds of women with pelvic inflammatory disease (PID). This review will focus on (1) the polymicrobial aetiologies of tubal factor infertility and (2) studies involved in screening for, and treatment and control of, Chlamydial infection to prevent PID and the associated sequelae of Fallopian tube inflammation that may lead to infertility and ectopic pregnancy.

Association between infant feeding patterns and diarrhoeal and respiratory illness: a cohort study in Chittagong, Bangladesh

Background In developing countries, infectious diseases such as diarrhoea and acute respiratory infections are the main cause of mortality and morbidity in infants aged less than one year. The importance of exclusive breastfeeding in the prevention of infectious diseases during infancy is well known. Although breastfeeding is almost universal in Bangladesh, the rates of exclusive breastfeeding remain low. This cohort study was designed to compare the prevalence of diarrhoea and acute respiratory infection (ARI) in infants according to their breastfeeding status in a prospective cohort of infants from birth to six months of age. Methods A total of 351 pregnant women were recruited in the Anowara subdistrict of Chittagong. Breastfeeding practices and the 7-day prevalence of diarrhoea and ARI were recorded at monthly home visits. Prevalences were compared using chi-squared tests and logistic regression. Results A total of 272 mother-infant pairs completed the study to six months. Infants who were exclusively breastfed for six months had a significantly lower 7-day prevalence of diarrhoea [AOR for lack of EBF = 2.50 (95%CI 1.10, 5.69), p = 0.03] and a significantly lower 7-day prevalence of ARI [AOR for lack of EBF = 2.31 (95%CI 1.33, 4.00), p < 0.01] than infants who were not exclusively breastfed. However, when the association between patterns of infant feeding (exclusive, predominant and partial breastfeeding) and illness was investigated in more detail, there was no significant difference in the prevalence of diarrhoea between exclusively [6.6% (95% CI 2.8, 10.4)] and predominantly breastfed infants [3.7% (95% CI 0.09, 18.3), (p = 0.56)]. Partially breastfed infants had a higher prevalence of diarrhoea than the others [19.2% (95% CI 10.4, 27.9), (p = 0.01)]. Similarly, although there was a large difference in prevalence in acute respiratory illness between exclusively [54.2% (95%CI 46.6, 61.8)] and predominantly breastfed infants [70.4% (95%CI 53.2, 87.6)] there was no significant difference in the prevalence (p = 0.17). Conclusion The findings suggest that exclusive or predominant breastfeeding can reduce rates of morbidity significantly in this region of rural Bangladesh.

Comparison of intranasal and transcutaneous immunization for induction of protective immunity against chlamydia muridarum respiratory tract infection

Chlamydia pneumoniae causes a range of respiratory infections including bronchitis, pharyngitis and pneumonia. Infection has also been implicated in exacerbation/initiation of asthma and chronic obstructive pulmonary disease (COPD) and may play a role in atherosclerosis and Alzheimer's disease. We have used a mouse model of Chlamydia respiratory infection to determine the effectiveness of intranasal (IN) and transcutaneous immunization (TCI) to prevent Chlamydia lung infection. Female BALB/c mice were immunized with chlamydial major outer membrane protein (MOMP) mixed with cholera toxin and CpG oligodeoxynucleotide adjuvants by either the IN or TCI routes. Serum and bronchoalveolar lavage (BAL) were collected for antibody analysis. Mononuclear cells from lung-draining lymph nodes were stimulated in vitro with MOMP and cytokine mRNA production determined by real time PCR. Animals were challenged with live Chlamydia and weighed daily following challenge. At day 10 (the peak of infection) animals were sacrificed and the numbers of recoverable Chlamydia in lungs determined by real time PCR. MOMP-specific antibody-secreting cells in lung tissues were also determined at day 10 post-infection. Both IN and TCI protected animals against weight loss compared to non-immunized controls with both immunized groups gaining weight by day 10-post challenge while controls had lost 6% of body weight. Both immunization protocols induced MOMP-specific IgG in serum and BAL while only IN immunization induced MOMP-specific IgA in BAL. Both immunization routes resulted in high numbers of MOMP-specific antibody-secreting cells in lung tissues (IN > TCI). Following in vitro re-stimulation of lung-draining lymph node cells with MOMP; IFNγ mRNA increased 20-fold in cells from IN immunized animals (compared to non-immunized controls) while IFNγ levels increased 6- to 7-fold in TCI animals. Ten days post challenge non-immunized animals had >7000 IFU in their lungs, IN immunized animals <50 IFU and TCI immunized animals <1500 IFU. Thus, both intranasal and transcutaneous immunization protected mice against respiratory challenge with Chlamydia. The best protection was obtained following IN immunization and correlated with IFNγ production by mononuclear cells in lung-draining LN and MOMP-specific IgA in BAL.

Detection of bacteriophage and respiratory viruses in droplets

Influenza is a widespread disease occurring in seasonal epidemics, and each year is responsible for up to 500,000 deaths worldwide. Influenza can develop into strains which cause severe symptoms and high mortality rates, and could potentially reach pandemic status if the virus’ properties allow easy transmission. Influenza is transmissible via contact with the virus, either directly (infected people) or indirectly (contaminated objects); via reception of large droplets over short distances (one metre or less); or through inhalation of aerosols containing the virus expelled by infected individuals during respiratory activities, that can remain suspended in the air and travel distances of more than one metre (the aerosol route). Aerosol transmission of viruses involves three stages: production of the droplets containing viruses; transport of the droplets and ability of a virus to remain intact and infectious; and reception of the droplets (via inhalation). Our understanding of the transmission of influenza viruses via the aerosol route is poor, and thus our ability to prevent a widespread outbreak is limited. This study explored the fate of viruses in droplets by investigating the effects of some physical factors on the recovery of both a bacteriophage model and influenza virus. Experiments simulating respiratory droplets were carried out using different types of droplets, generated from a commonly used water-like matrix, and also from an ‘artificial mucous’ matrix which was used to more closely resemble respiratory fluids. To detect viruses in droplets, we used the traditional plaque assay techniques, and also a sensitive, quantitative PCR assay specifically developed for this study. Our results showed that the artificial mucous suspension enhanced the recovery of infectious bacteriophage. We were able to report detection limits of infectious bacteriophage (no bacteriophage was detected by the plaque assay when aerosolised from a suspension of 103 PFU/mL, for three of the four droplet types tested), and that bacteriophage could remain infectious in suspended droplets for up to 20 minutes. We also showed that the nested real-time PCR assay was able to detect the presence of bacteriophage RNA where the plaque assay could not detect any intact particles. Finally, when applying knowledge from the bacteriophage experiments, we reported the quantitative recoveries of influenza viruses in droplets, which were more consistent and stable than we had anticipated. Influenza viruses can be detected up to 20 minutes (after aerosolisation) in suspended aerosols and possibly beyond. It also was detectable from nebulising suspensions with relatively low concentrations of viruses.

Policy analysis of disaster health management in China

Humankind has been dealing with all kinds of disasters since the dawn of time. The risk and impact of disasters producing mass casualties worldwide is increasing, due partly to global warming as well as to increased population growth, increased density and the aging population. China, as a country with a large population, vast territory, and complex climatic and geographical conditions, has been plagued by all kinds of disasters. Disaster health management has traditionally been a relatively arcane discipline within public health. However, SARS, Avian Influenza, and earthquakes and floods, along with the need to be better prepared for the Olympic Games in China has brought disasters, their management and their potential for large scale health consequences on populations to the attention of the public, the government and the international community alike. As a result significant improvements were made to the disaster management policy framework, as well as changes to systems and structures to incorporate an improved disaster management focus. This involved the upgrade of the Centres for Disease Control and Prevention (CDC) throughout China to monitor and better control the health consequences particularly of infectious disease outbreaks. However, as can be seen in the Southern China Snow Storm and Wenchuan Earthquake in 2008, there remains a lack of integrated disaster management and efficient medical rescue, which has been costly in terms of economics and health for China. In the context of a very large and complex country, there is a need to better understand whether these changes have resulted in effective management of the health impacts of such incidents. To date, the health consequences of disasters, particularly in China, have not been a major focus of study. The main aim of this study is to analyse and evaluate disaster health management policy in China and in particular, its ability to effectively manage the health consequences of disasters. Flood has been selected for this study as it is a common and significant disaster type in China and throughout the world. This information will then be used to guide conceptual understanding of the health consequences of floods. A secondary aim of the study is to compare disaster health management in China and Australia as these countries differ in their length of experience in having a formalised policy response. The final aim of the study is to determine the extent to which Walt and Gilson’s (1994) model of policy explains how disaster management policy in China was developed and implemented after SARS in 2003 to the present day. This study has utilised a case study methodology. A document analysis and literature search of Chinese and English sources was undertaken to analyse and produce a chronology of disaster health management policy in China. Additionally, three detailed case studies of flood health management in China were undertaken along with three case studies in Australia in order to examine the policy response and any health consequences stemming from the floods. A total of 30 key international disaster health management experts were surveyed to identify fundamental elements and principles of a successful policy framework for disaster health management. Key policy ingredients were identified from the literature, the case-studies and the survey of experts. Walt and Gilson (1994)’s policy model that focuses on the actors, content, context and process of policy was found to be a useful model for analysing disaster health management policy development and implementation in China. This thesis is divided into four parts. Part 1 is a brief overview of the issues and context to set the scene. Part 2 examines the conceptual and operational context including the international literature, government documents and the operational environment for disaster health management in China. Part 3 examines primary sources of information to inform the analysis. This involves two key studies: • A comparative analysis of the management of floods in China and Australia • A survey of international experts in the field of disaster management so as to inform the evaluation of the policy framework in existence in China and the criteria upon which the expression of that policy could be evaluated Part 4 describes the key outcomes of this research which include: • A conceptual framework for describing the health consequences of floods • A conceptual framework for disaster health management • An evaluation of the disaster health management policy and its implementation in China. The research outcomes clearly identified that the most significant improvements are to be derived from improvements in the generic management of disasters, rather than the health aspects alone. Thus, the key findings and recommendations tend to focus on generic issues. The key findings of this research include the following: • The health consequences of floods may be described in terms of time as ‘immediate’, ‘medium term’ and ‘long term’ and also in relation to causation as ‘direct’ and ‘indirect’ consequences of the flood. These two aspects form a matrix which in turn guides management responses. • Disaster health management in China requires a more comprehensive response throughout the cycle of prevention, preparedness, response and recovery but it also requires a more concentrated effort on policy implementation to ensure the translation of the policy framework into effective incident management. • The policy framework in China is largely of international standard with a sound legislative base. In addition the development of the Centres for Disease Control and Prevention has provided the basis for a systematic approach to health consequence management. However, the key weaknesses in the current system include: o The lack of a key central structure to provide the infrastructure with vital support for policy development, implementation and evaluation. o The lack of well-prepared local response teams similar to local government based volunteer groups in Australia. • The system lacks structures to coordinate government action at the local level. The result of this is a poorly coordinated local response and lack of clarity regarding the point at which escalation of the response to higher levels of government is advisable. These result in higher levels of risk and negative health impacts. The key recommendations arising from this study are: 1. Disaster health management policy in China should be enhanced by incorporating disaster management considerations into policy development, and by requiring a disaster management risk analysis and disaster management impact statement for development proposals. 2. China should transform existing organizations to establish a central organisation similar to the Federal Emergency Management Agency (FEMA) in the USA or the Emergency Management Australia (EMA) in Australia. This organization would be responsible for leading nationwide preparedness through planning, standards development, education and incident evaluation and to provide operational support to the national and local government bodies in the event of a major incident. 3. China should review national and local plans to reflect consistency in planning, and to emphasize the advantages of the integrated planning process. 4. Enhance community resilience through community education and the development of a local volunteer organization. China should develop a national strategy which sets direction and standards in regard to education and training, and requires system testing through exercises. Other initiatives may include the development of a local volunteer capability with appropriate training to assist professional response agencies such as police and fire services in a major incident. An existing organisation such as the Communist Party may be an appropriate structure to provide this response in a cost effective manner. 5. Continue development of professional emergency services, particularly ambulance, to ensure an effective infrastructure is in place to support the emergency response in disasters. 6. Funding for disaster health management should be enhanced, not only from government, but also from other sources such as donations and insurance. It is necessary to provide a more transparent mechanism to ensure the funding is disseminated according to the needs of the people affected. 7. Emphasis should be placed on prevention and preparedness, especially on effective disaster warnings. 8. China should develop local disaster health management infrastructure utilising existing resources wherever possible. Strategies for enhancing local infrastructure could include the identification of local resources (including military resources) which could be made available to support disaster responses. It should develop operational procedures to access those resources. Implementation of these recommendations should better position China to reduce the significant health consequences experienced each year from major incidents such as floods and to provide an increased level of confidence to the community about the country’s capacity to manage such events.

Room ventilation and the risk of airborne infection transmission in three health care settings within a large teaching hospital

Background: Room ventilation is a key determinant of airborne disease transmission. Despite this, ventilation guidelines in hospitals are not founded on robust scientific evidence related to prevention of airborne transmission. Methods: We sought to assess the effect of ventilation rates on influenza, tuberculosis (TB) and rhinovirus infection risk within three distinct rooms in a major urban hospital; a Lung Function Laboratory, Emergency Department (ED) Negative-pressure Isolation Room and an Outpatient Consultation Room were investigated. Air exchange rate measurements were performed in each room using CO2 as a tracer. Gammaitoni and Nucci’s model was employed to estimate infection risk. Results: Current outdoor air exchange rates in the Lung Function Laboratory and ED Isolation Room limited infection risks to between 0.1 and 3.6%. Influenza risk for individuals entering an Outpatient Consultation Room after an infectious individual departed ranged from 3.6 to 20.7%, depending on the duration for which each person occupied the room. Conclusions: Given the absence of definitive ventilation guidelines for hospitals, air exchange measurements combined with modelling afford a useful means of assessing, on a case-by-case basis, the suitability of room ventilation at preventing airborne disease transmission.

Blood cultures for assessment of postoperative fever in arthroplasty patients

Postoperative fever in arthroplasty patients is common. The value of diagnostic workup of fever in this instance is of questionable utility. Studies have shown that blood cultures in this scenario add little to clinical management, but sample sizes have been small and the use of blood cultures in this setting continues. This study aimed to examine the value of blood cultures in the assessment of postoperative fever in a large arthroplasty population. The medical records of 101 patients who had 141 blood culture sets taken during a 2-year period were retrospectively analyzed. Of the 141 blood culture sets, only 2 returned positive results. These were both thought to be as a result of skin contamination at the time of venipuncture. No infectious sequelae occurred in either patient. We conclude that blood cultures have no role to play in the assessment of the febrile, otherwise asymptomatic arthroplasty patient in the early postoperative period.

The health of women and girls determines the health and well-being of our modern world : a white paper from the International Council on Women's Health Issues

The International Council on Women's Health Issues (ICOWHI) is an international nonprofit association dedicated to the goal of promoting health, health care, and well-being of women and girls throughout the world through participation, empowerment, advocacy, education, and research. We are a multidisciplinary network of women's health providers, planners, and advocates from all over the globe. We constitute an international professional and lay network of those committed to improving women and girl's health and quality of life. This document provides a description of our organization mission, vision, and commitment to improving the health and well-being of women and girls globally.

Comparative study of coagulase negative Staphylococci (CoNS) from clinical isolates, skin and nasal sources

Staphylococci are important pathogenic bacteria responsible for a range of diseases in humans. The most frequently isolated microorganisms in a hospital microbiology laboratory are staphylococci. The general classification of staphylococci divides them into two major groups; Coagulase-positive staphylococci (e.g. Staphylococcus aureus) and Coagulase-negative staphylococci (e.g. Staphylococcus epidermidis). Coagulase-negative staphylococcal (CoNS) isolates include a variety of species and many different strains but are often dominated by the most important organism of this group, S. epidermidis. Currently, these organisms are regarded as important pathogenic organisms causing infections related to prosthetic materials and surgical wounds. A significant number of S. epidermidis isolates are also resistant to different antimicrobial agents. Virulence factors in CoNS are not very clearly established and not well documented. S. epidermidis is evolving as a resistant and powerful microbe related to nosocomial infections because it has different properties which independently, and in combination, make it a successful infectious agent, especially in the hospital environment. Such characteristics include biofilm formation, drug resistance and the evolution of genetic variables. The purpose of this project was to develop a novel SNP genotyping method to genotype S. epidermidis strains originating from hospital patients and healthy individuals. High-Resolution Melt Analysis was used to assign binary typing profiles to both clinical and commensal strains using a new bioinformatics approach. The presence of antibiotic resistance genes and biofilm coding genes were also interrogated in these isolates.

Chlamydia

Chlamydial infections of humans can cause blindness and infertility as a result of diseases such as keratoconjunctivitis (trachoma), urethritis and cervicitis. However, in greater than half of all chlamydial diseases in males and females there are no signs or symptoms of infection. Chlamydia trachomatis is the causative bacterial organism responsible for the global estimate of 40.6 million people currently suffering with active trachoma and for the five million new cases of sexually transmitted infections each year in the United States of America. Even though antibiotics are available to treat Chlamydia, the incidence of each of these primarily asymptomatic infections continues to increase. In this Chapter we review the current knowledge of C.trachomatis including clinicial diseases and sequelae, the chlamydial developmental cycle in vivo, immunobiology and immune responses to infections, chlamydial genomics and vaccine development.

Evaluation of novel Streptococcus pyogenes vaccine candidates incorporating multiple conserved sequences from the C-repeat region of the M-protein

A major challenge for Streptococcus pyogenes vaccine development is the identification of epitopes that confer protection from infection by multiple S. pyogenes M-types. Here we have identified and characterised the distribution of common variant sequences from individual repeat units of the C-repeat region (CRR) of M-proteins representing 77 different M-types. Three polyvalent fusion vaccine candidates (SV1, SV2 and SV3) incorporating the most common variants were subsequently expressed and purified, and demonstrated to be alpha-helical by Circular Dichroism (CD), a secondary conformational characteristic of the CRR in the M-protein. Antibodies raised against each of these constructs recognise M-proteins that vary in their CRR, and bind to the surface of multiple S. pyogenes isolates. Antibodies raised against SV1, containing five variant sequences, also kill heterologous S. pyogenes isolates in in vitro bactericidal assays. Further structural characterisation of this construct demonstrated the conformation of SV1 was stable at different pHs, and thermal unfolding of SV1 a reversible process. Our findings demonstrate that linkage of multiple variant sequences into a single recombinant construct overcomes the need to embed the variant sequences in foreign helix promoting flanking sequences for conformational stability, and demonstrates the viability of the polyvalent candidates as global S. pyogenes vaccine candidates.

Socio-economic differences in takeaway food consumption among adults

To examine socioeconomic differences in the frequency and types of takeaway foods consumed. Cross-sectional postal survey. Participants were asked about their usual consumption of overall takeaway food (< four times a month, or ≥ four times a month) and 22 specific takeaway food items (< once a month, or ≥ once a month): these latter foods were grouped into “healthy” and “less healthy” choices. Socioeconomic position was measured using education and equivalised household income and differences in takeaway food consumption were assessed by calculating prevalence ratios using log binomial regression. Adults aged 25–64 years from Brisbane, Australia were randomly selected from the electoral roll (N = 903, 63.7% response rate). Compared with their more educated counterparts, the least educated were more regular consumers of overall takeaway food, fruit/vegetable juice, and less regular consumers of sushi. For the “less healthy” items, the least educated more regularly consumed potato chips, savoury pies, fried chicken, and non-diet soft drinks; however, the least educated were less likely to consume curry. Household income was not associated with overall takeaway consumption. The lowest income group were more regular consumers of fruit/vegetable juice compared with the highest income group. Among the “less healthy” items, the lowest income group were more regular consumers of fried fish, ice-cream, and milk shakes, while curry was consumed less regularly. The frequency and types of takeaway foods consumed by socioeconomically disadvantaged groups may contribute to inequalities in overweight/obesity and chronic disease.