Saliva as an emerging biofluid for clinical diagnosis and applications of MEMS/NEMS in salivary diagnostics

Saliva as a biological fluid is gaining wider acceptance for diagnosing diseases. The growing interest in saliva as a biological fluid is due to its noninvasiveness, ease of use, cost-effectiveness, and multiple sample collection possibilities as well as minimal risk to health care professionals of contracting infectious organisms such as HIV and Hep B. However, the clinical translation of saliva is hampered by our lack of understanding of the biomolecular transportation from blood into saliva, the diurnal variations of biomolecules present in saliva, and relatively low levels of analytes (100th to a 1000th fold less than in blood). We provide information on the current status of salivary research, salivary diagnostics empowered by nanotechnology, and future prospects in this emerging field of saliva diagnostics.

Healthcare-associated infections in Australia : time for national surveillance

Abstract Objective. Healthcare-associated infection (HAI) surveillance programs are critical for infection prevention. Australia does not have a comprehensive national HAI surveillance program. The purpose of this paper is to provide an overview of established international and Australian statewide HAI surveillance programs and recommend a pathway for the development of a national HAI surveillance program in Australia. Methods. This study examined existing HAI surveillance programs through a literature review, a review of HAI surveillance program documentation, such as websites, surveillance manuals and data reports and direct contact with program representatives. Results. Evidence from international programs demonstrates national HAI surveillance reduces the incidence of HAIs. However, the current status of HAI surveillance activity in Australian states is disparate, variation between programs is not well understood, and the quality of data currently used to compose national HAI rates is uncertain. Conclusions. There is a need to develop a well-structured, evidence-based national HAI program in Australia to meet the increasing demand for validated reliable national HAI data. Such a program could be leveraged off the work of existing Australian and international programs.

Can a text message a week improve breastfeeding?

Background Breastfeeding is recognised as the optimal method for feeding infants with health gains made by reducing infectious diseases in infancy; and chronic diseases, including obesity, in childhood, adolescence and adulthood. Despite this, exclusivity and duration in developed countries remains resistant to improvement. The objectives of this research were to test if an automated mobile phone text messaging intervention, delivering one text message a week, could increase “any” breastfeeding rates and improve breastfeeding self-efficacy and coping. Methods Women were eligible to participate if they were: over eighteen years; had an infant less than three months old; were currently breastfeeding; no diagnosed mental illness; and used a mobile phone . Women in the intervention group received MumBubConnect, a text messaging service with automated responses delivered once a week for 8 weeks. Women in the comparison group received their usual care and were sampled two years after the intervention group. Data collection included online surveys at two time points, week zero and week nine, to measure breastfeeding exclusivity and duration, coping, emotions, accountability and self-efficacy. A range of statistical analyses were used to test for differences between groups. Hierarchical regression was used to investigate change in breastfeeding outcome, between groups, adjusting for co-variates. Results The intervention group had 120 participants at commencement and 114 at completion, the comparison group had 114 participants at commencement and 86 at completion. MumBubConnect had a positive impact on the primary outcome of breastfeeding behaviors with women receiving the intervention more likely to continue exclusive breastfeeding; with a 6% decrease in exclusive breastfeeding in the intervention group, compared to a 14% decrease in the comparison group (p < 0.001). This remained significant after controlling for infant age, mother’s income, education and delivery type (p = 0.04). Women in the intervention group demonstrated active coping and were less likely to display emotions-focussed coping (p < .001). There was no discernible statistical effect on self-efficacy or accountability. Conclusions A fully automated text messaging services appears to improve exclusive breastfeeding duration. The service provides a well-accepted, personalised support service that empowers women to actively resolve breastfeeding issues. Trial registration Australian New Zealand Clinical Trials Registry: ACTRN12614001091695.

Antimicrobial stewardship activities : a survey of Queensland hospitals

Objective: In 2011, the Australian Commission on Safety and Quality in Health Care (ACSQHC) recommended that all hospitals in Australia must have an Antimicrobial Stewardship (AMS) program by 2013. Nevertheless, little is known about current AMS activities. This study aimed to determine the AMS activities currently undertaken, and to identify gaps, barriers to implementation and opportunities for improvement in Queensland hospitals. Methods: The AMS activities of 26 facilities from 15 hospital and health services in Queensland were surveyed during June 2012 to address strategies for effective AMS: implementing clinical guidelines, formulary restriction, reviewing antimicrobial prescribing, auditing antimicrobial use and selective reporting of susceptibility results. Results: The response rate was 62%. Nineteen percent had an AMS team (a dedicated multidisciplinary team consisting of a medically trained staff member and a pharmacist). All facilities had access to an electronic version of Therapeutic Guidelines: Antibiotic, with a further 50% developing local guidelines for antimicrobials. One-third of facilities had additional restrictions. Eighty-eight percent had advice for restricted antimicrobials from in-house infectious disease physicians or clinical microbiologists. Antimicrobials were monitored with feedback given to prescribers at point of care by 76% of facilities. Deficiencies reported as barriers to establishing AMS programs included: pharmacy resources, financial support by hospital management, and training and education in antimicrobial use. Conclusions: Several areas for improvement were identified: reviewing antimicrobial prescribing with feedback to the prescriber, auditing, and training and education in antimicrobial use. There also appears to be a lack of resources to support AMS programs in some facilities. What is known about the topic? The ACSQHC has recommended that all hospitals implement an AMS program by 2013 as a requirement of Standard 3 (Preventing and Controlling Healthcare-Associated Infections) of the National Safety and Quality Health Service Standards. The intent of AMS is to ensure appropriate prescribing of antimicrobials as part of the broader systems within a health service organisation to prevent and manage healthcare-associated infections, and improve patient safety and quality of care. This criterion also aligns closely with Standard 4: Medication Safety. Despite this recommendation, little is known about what AMS activities are undertaken in these facilities and what additional resources would be required in order to meet these national standards. What does the paper add? This is the first survey that has been conducted of public hospital and health services in Queensland, a large decentralised state in Australia. This paper describes what AMS activities are currently being undertaken, identifies practice gaps, barriers to implementation and opportunities for improvement in Queensland hospitals. What are the implications for practitioners? Several areas for improvement such as reviewing antimicrobial prescribing with feedback to the prescriber, auditing, and training and education in antimicrobial use have been identified. In addition, there appears to be a lack of resources to support AMS programs in some facilities.

Preventing infections through cleaner hospitals project

While many Australian hospitals have good infection control practices, research about the role cleaning in the hospital environment plays in preventing infections is limited.

Changes in healthcare-associated infections after the introduction of a national hand hygiene initiative

Introduction: Interventions that prevent healthcare-associated infections should lead to fewer deaths and shorter hospital stays. Cleaning hands with soap and water or alcohol rub is an effectiveway to prevent the transmission of organisms, but compliance is sometimes low. The National Hand Hygiene Initiative in Australia aimed to improve hand hygiene compliance among healthcare workers, with the goal of reducing rates of healthcare-associated infections. Methods: We examined if the introduction of the National Hand Hygiene Initiative was associated with a change in infection rates. Monthly infection rates for six types of healthcare-associated infections were examined in 38 Australian hospitals across six states. Infection categories were: bloodstream infections, centralline associated bloodstream infections, methicillin-resistant and methicillin-sensitive Staphylococcus aureus, Staphylococcus aureus bacteraemia and surgical site infections. Results: The National Hand Hygiene Initiative was associated with a statistically significant reduction in infection rates in 11 out of 23 state and infection combinations studied. There was no change in infection rates for nine combinations, and there was an increase in three infection rates in South Australia. Conclusions: The intervention was associated with reduced infection rates in many cases. The lack of improvement in nine cases may have been because they already had effective initiatives before the national initiative’s introduction.

Circulating antibodies against Plasmodium falciparum histidine-rich proteins 2 interfere with antigen detection by rapid diagnostic tests

Background Rapid diagnostic tests (RDTs) for detection of Plasmodium falciparum infection that target P. falciparum histidine-rich protein 2 (PfHRP2), a protein that circulates in the blood of patients infected with this species of malaria, are widely used to guide case management. Understanding determinants of PfHRP2 availability in circulation is therefore essential to understanding the performance of PfHRP2-detecting RDTs. Methods The possibility that pre-formed host anti-PfHRP2 antibodies may block target antigen detection, thereby causing false negative test results was investigated in this study. Results Anti-PfHRP2 antibodies were detected in 19/75 (25%) of plasma samples collected from patients with acute malaria from Cambodia, Nigeria and the Philippines, as well as in 3/28 (10.7%) asymptomatic Solomon Islands residents. Pre-incubation of plasma samples from subjects with high-titre anti-PfHRP2 antibodies with soluble PfHRP2 blocked the detection of the target antigen on two of the three brands of RDTs tested, leading to false negative results. Pre-incubation of the plasma with intact parasitized erythrocytes resulted in a reduction of band intensity at the highest parasite density, and a reduction of lower detection threshold by ten-fold on all three brands of RDTs tested. Conclusions These observations indicate possible reduced sensitivity for diagnosis of P. falciparum malaria using PfHRP2-detecting RDTs among people with high levels of specific antibodies and low density infection, as well as possible interference with tests configured to detect soluble PfHRP2 in saliva or urine samples. Further investigations are required to assess the impact of pre-formed anti-PfHRP2 antibodies on RDT performance in different transmission settings.

Evidence for an Auditory Fovea in the New Zealand Kiwi (Apteryx mantelli).

Kiwi are rare and strictly protected birds of iconic status in New Zealand. Yet, perhaps due to their unusual, nocturnal lifestyle, surprisingly little is known about their behaviour or physiology. In the present study, we exploited known correlations between morphology and physiology in the avian inner ear and brainstem to predict the frequency range of best hearing in the North Island brown kiwi. The mechanosensitive hair bundles of the sensory hair cells in the basilar papilla showed the typical change from tall bundles with few stereovilli to short bundles with many stereovilli along the apical-to-basal tonotopic axis. In contrast to most birds, however, the change was considerably less in the basal half of the epithelium. Dendritic lengths in the brainstem nucleus laminaris also showed the typical change along the tonotopic axis. However, as in the basilar papilla, the change was much less pronounced in the presumed high-frequency regions. Together, these morphological data suggest a fovea-like overrepresentation of a narrow high-frequency band in kiwi. Based on known correlations of hair-cell microanatomy and physiological responses in other birds, a specific prediction for the frequency representation along the basilar papilla of the kiwi was derived. The predicted overrepresentation of approximately 4-6 kHz matches potentially salient frequency bands of kiwi vocalisations and may thus be an adaptation to a nocturnal lifestyle in which auditory communication plays a dominant role.

Surveillance snapshot of Clostridium difficile infection in hospitals across Queensland detects binary toxin producing ribotype UK 244

In North America and Europe, the binary toxin positive Clostridium difficile strains of the ribotypes 027 and 078 have been associated with death, toxic megacolon and other adverse outcomes. Following an increase in C. difficile infections (CDIs) in Queensland, a prevalence study involving 175 hospitals was undertaken in early 2012, identifying 168 cases of CDI over a 2 month period. Patient demographics and clinical characteristics were recorded, and C. difficile isolates were ribotyped and tested for the presence of binary toxin genes. Most patients (106/168, 63.1%) were aged over 60 years. Overall, 98 (58.3%) developed symptoms after hospitalisation; 89 cases (53.0%) developed symptoms more than 48 hours after admission. Furthermore, 27 of the 62 (67.7%) patients who developed symptoms in the community ad been hospitalised within the last 3 months. Thirteen of the 168 (7.7%) cases identified had severe disease, resulting in admission to the Intensive Care Unit or death within 30 days of the onset of symptoms. The 3 most common ribotypes isolated were UK 002 (22.9%), UK 014 (13.3%) and the binary toxin-positive ribotype UK 244 (8.4%). The only other binary toxin positive ribotype isolated was UK 078 (n = 1). Of concern was the detection of the binary toxin positive ribotype UK 244, which has recently been described in other parts of Australia and New Zealand. No isolates were of the international epidemic clone of ribotype UK 027, although ribotype UK 244 is genetically related to this clone. Further studies are required to track the epidemiology of ribotype UK 244 in Australia and New Zealand. Commun Dis Intell 2014;38(4):E279–E284.

Promiscuity, pheromones and pathogenicity : why all Enterococci are not created equal

Enterococcus faecalis is a Gram-positive, coccus shaped, lactic acid bacterium, with demonstrated ubiquity across multiple anatomical sites. Enterococcus faecalis isolates have been isolated from clinical samples as the etiological agent in patients with overt infections, and from body sites previously thought to be sterile but absent of signs and symptoms of infection. E. faecalis is implicated in both human health and disease, recognized as a commensal, a probiotic and an opportunistic multiply resistant pathogen. E. faecalis has emerged as a key pathogen in nosocomial infections. E. faecalis is well equipped to avert recognition by host cell immune mediators. Antigenic cell wall components including lipotechoic acids are concealed from immune detection by capsular polysaccharides produced by some strains. Thereby preventing complement activation, the pro-inflammatory response, opsonisation and phagocytosis. E. faecalis also produces a suite of enzymes including gelatinase and cytolysin, which aid in both virulence and host immune evasion. The ability of enterococci to form biofilms in vivo further increases virulence, whilst simultaneously preventing detection by host cells. E. faecalis exhibits high levels of both intrinsic and acquired antimicrobial resistance. The mobility of the E. faecalis genome is a significant contributor to antimicrobial resistance, with this species also transferring resistance to other Gram-positive bacteria. Whilst E. faecalis is of increasing concern in nosocomial infections, its role as a member of the endogenous microbiota cannot be underestimated. As a commensal and probiotic, E. faecalis plays an integral role in modulating the immune response, and in providing endogenous antimicrobial activity to enhance exclusion or inhibition of opportunistic pathogens in certain anatomical niches. In this chapter we will review possible mediators of enterococcal transition from commensal microbe to opportunistic pathogen, considering isolates obtained from patients diagnosed with pathogenic infections and those obtained from asymptomatic patients.

Prevalence of methicillin resistance and virulence determinants of Staphylococcus aureus in diabetic foot ulcers

Background Diabetic foot ulceration (DFU) is a multifactorial process and is responsible for considerable morbidity and contributes to the increasing cost of health care worldwide. The diagnosis and identification of these ulcers remains a complex problem. Bacterial infection is promoted in the diabetic foot wound by decreased vascular supply and impaired host immune response. As conventional clinical microbiological methods are time-consuming and only identifies about 1% of the wound microbiota, detection of bacteria present in DFUs using molecular methods is highly advantageous and efficient. The aim of this study was to assess the virulence and methicillin resistance profiles of Staphylococcus aureus detected in DFUs using DNA-based methods. Methods A total of 223 swab samples were collected from 30 patients from March to October 2012. Bacterial DNA was extracted from the swab samples using standard procedures and was used to perform polymerase chain reaction (PCR) using specific oligonucleotide primers. The products were visualized using agarose gel electrophoresis. Results S. aureus was detected in 44.8% of samples. 25% of the S. aureus was methicillin-resistant S. aureus harboring the mecA gene. The alpha-toxin gene was present in 85% of the S. aureus positive samples. 61% of the S. aureus present in DFU samples harbored the exfoliatin factor A gene. Both the fibronectin factor A and fibronectin factor B gene were detected in 71% and 74% of the S. aureus positive samples. Conclusions DNA-based detection and characterization of bacteria in DFUs are rapid and efficient and can assist in accurate, targeted antibiotic therapy of DFU infections. The majority of S. aureus detected in this study were highly virulent and also resistant to methicillin. Further studies are required to understand the role of S. aureus in DFU trajectory.

The use of prescribed drugs for common chronic conditions in South Africa in 1998

Purpose To determine the prescribed drug-utilisation pattern for six common chronic conditions in adult South Africans in a cross-sectional survey. Methods 13 826 randomly selected participants, 15 years and older, were surveyed by trained fieldworkers at their homes in 1998. Questionnaires included socio-demographic, chronic-disease and drug-use data. The prescribed drugs were recorded from participants' medication containers. The Anatomical Therapeutic Classification (ATC) code of the drugs for tuberculosis (TB), diabetes, hypertension, hyperlipidaemia, other atherosclerosis-related conditions, such as heart conditions or cerebrovascular accidents (CVA), and asthma or chronic obstructive pulmonary disease (COPD), was recorded. The use of logistic regression analyses identified the determinants of those patients who used prescription medication for these six conditions. Results 18.4% of the women and 12.5% of the men used drugs for the six chronic conditions. Men used drugs most frequently for hypertension (50.9%) and asthma or chronic bronchitis (24.3%), while in women it was for hypertension (59.9%) and diabetes (17.5%). The logistic regression analyses showed that women, wealthier and older people, and those with medical insurance used these chronic-disease drugs more frequently compared to men, younger or poor people, or those without medical insurance. The African population group used these drugs less frequently than any other ethnic group. The inappropriate use of methyldopa was found for 14.8% of all antihypertensive drugs, while very few people used aspirin. Conclusions The methodology of this study provides a means of ascertaining the chronic-disease drug-utilisation pattern in national health surveys. The pattern described, suggests an inequitable use of chronic-disease drugs and inadequate use of some effective drugs to control the burden of chronic diseases in South Africa. Copyright © 2004 John Wiley & Sons, Ltd.

Mitochondrial membrane potential in a small subset of artemisinin-induced dormant plasmodium falciparum parasites in vitro

Artemisinin induced dormancy is a proposed mechanism for failures of mono-therapy and is linked with artemisinin resistance in Plasmodium falciparum. The biological characterization and dynamics of dormant parasites are not well understood. Here we report that following dihydroartemisinin (DHA) treatment in vitro, a small subset of morphologically dormant parasites was stained with rhodamine 123 (RH), a mitochondrial membrane potential (MMP) marker, and persisted to recovery. FACS sorted RH-positive parasites resumed growth at 10,000/well while RH-negative parasites failed to recover at 5 million/well. Furthermore, transcriptional activity for mitochondrial enzymes was only detected in RH-positive dormant parasites. Importantly, after treating dormant parasites with different concentrations of atovaquone, a mitochondrial inhibitor, the recovery of dormant parasites was delayed or stopped. This demonstrates that mitochondrial activity is critical for survival and regrowth of dormant parasites and that RH staining provides a means of identifying these parasites. These findings provide novel paths for studying and eradicating this dormant stage.

A simulation model of the within-host dynamics of Plasmodium vivax infection

Background The benign reputation of Plasmodium vivax is at odds with the burden and severity of the disease. This reputation, combined with restricted in vitro techniques, has slowed efforts to gain an understanding of the parasite biology and interaction with its human host. Methods A simulation model of the within-host dynamics of P. vivax infection is described, incorporating distinctive characteristics of the parasite such as the preferential invasion of reticulocytes and hypnozoite production. The developed model is fitted using digitized time-series’ from historic neurosyphilis studies, and subsequently validated against summary statistics from a larger study of the same population. The Chesson relapse pattern was used to demonstrate the impact of released hypnozoites. Results The typical pattern for dynamics of the parasite population is a rapid exponential increase in the first 10 days, followed by a gradual decline. Gametocyte counts follow a similar trend, but are approximately two orders of magnitude lower. The model predicts that, on average, an infected naïve host in the absence of treatment becomes infectious 7.9 days post patency and is infectious for a mean of 34.4 days. In the absence of treatment, the effect of hypnozoite release was not apparent as newly released parasites were obscured by the existing infection. Conclusions The results from the model provides useful insights into the dynamics of P. vivax infection in human hosts, in particular the timing of host infectiousness and the role of the hypnozoite in perpetuating infection.