Persistent chlamydial infections : role in inflammation and challenges for vaccine development.

The development of chlamydial vaccines continues to be a major challenge for researchers. While acute infections are the main target of vaccine development groups, Chlamydia is well known for its ability to establish chronic or persistent infections in its host. To date, little effort has focussed specifically on the challenges of vaccines to successfully combat the chronic or persistent phase of the disease and yet this will be a necessary aspect of any fully successful chlamydial vaccine. This short review specifically examines the phenomenon of chlamydial persistence and the unique challenges that this brings to vaccine development.

Spatial analysis of notified cryptosporidiosis infections in Brisbane, Australia

Purpose: This study explored the spatial distribution of notified cryptosporidiosis cases and identified major socioeconomic factors associated with the transmission of cryptosporidiosis in Brisbane, Australia. Methods: We obtained the computerized data sets on the notified cryptosporidiosis cases and their key socioeconomic factors by statistical local area (SLA) in Brisbane for the period of 1996 to 2004 from the Queensland Department of Health and Australian Bureau of Statistics, respectively. We used spatial empirical Bayes rates smoothing to estimate the spatial distribution of cryptosporidiosis cases. A spatial classification and regression tree (CART) model was developed to explore the relationship between socioeconomic factors and the incidence rates of cryptosporidiosis. Results: Spatial empirical Bayes analysis reveals that the cryptosporidiosis infections were primarily concentrated in the northwest and southeast of Brisbane. A spatial CART model shows that the relative risk for cryptosporidiosis transmission was 2.4 when the value of the social economic index for areas (SEIFA) was over 1028 and the proportion of residents with low educational attainment in an SLA exceeded 8.8%. Conclusions: There was remarkable variation in spatial distribution of cryptosporidiosis infections in Brisbane. Spatial pattern of cryptosporidiosis seems to be associated with SEIFA and the proportion of residents with low education attainment.

Continuous infusion of ticarcillin-clavulanate for home treatment of serious infections : clinical efficacy, safety, pharmacokinetics and pharmacodynamics

Continuous infusion (CI) ticarcillin–clavulanate is a potential therapeutic improvement over conventional intermittent dosing because the major pharmacodynamic (PD) predictor of efficacy of β-lactams is the time that free drug levels exceed the MIC. This study incorporated a 6-year retrospective arm evaluating efficacy and safety of CI ticarcillin–clavulanate in the home treatment of serious infections and a prospective arm additionally evaluating pharmacokinetics (PK) and PD. In the prospective arm, steady-state serum ticarcillin and clavulanate levels and MIC testing of significant pathogens were performed. One hundred and twelve patients (median age, 56 years) were treated with a CI dose of 9.3–12.4 g/day and mean CI duration of 18.0 days. Infections treated included osteomyelitis (50 patients), septic arthritis (6), cellulitis (17), pulmonary infections (12), febrile neutropenia (7), vascular infections (7), intra-abdominal infections (2), and Gram-negative endocarditis (2); 91/112 (81%) of patients were cured, 14 (13%) had partial response and 7 (6%) failed therapy. Nine patients had PICC line complications and five patients had drug adverse events. Eighteen patients had prospective PK/PD assessment although only four patients had sufficient data for a full PK/PD evaluation (both serum steady-state drug levels and ticarcillin and clavulanate MICs from a bacteriological isolate), as this was difficult to obtain in home-based patients, particularly as serum clavulanate levels were found to deteriorate rapidly on storage. Three of four patients with matched PK/PD assessment had free drug levels exceeding the MIC of the pathogen. Home CI of ticarcillin–clavulanate is a safe, effective, convenient and practical therapy and is a therapeutic advance over traditional intermittent dosing when used in the home setting.

Human papillomavirus DNA detected in peripheral blood samples from healthy Australian male blood donors

Recent studies have shown that human papillomavirus (HPV) DNA can be found in circulating blood, including peripheral blood mononuclear cells (PBMCs), sera, plasma, and arterial cord blood. In light of these findings, DNA extracted from PBMCs from healthy blood donors were examined in order to determine how common HPV DNA is in blood of healthy individuals. Blood samples were collected from 180 healthy male blood donors (18-76 years old) through the Australian Red Cross Blood Services. Genomic DNA was extracted and specimens were tested for HPV DNA by PCR using a broad range primer pair. Positive samples were HPV-type determined by cloning and sequencing. HPV DNA was found in 8.3% (15/180) of the blood donors. A wide variety of different HPV types were isolated from the PBMCs; belonging to the cutaneous beta and gamma papillomavirus genera and mucosal alpha papillomaviruses. High-risk HPV types that are linked to cancer development were detected in 1.7% (3/180) of the PBMCs. Blood was also collected from a healthy HPV-positive 44-year-old male on four different occasions in order to determine which blood cell fractions harbor HPV. PBMCs treated with trypsin were negative for HPV, while non-trypsinized PBMCs were HPV-positive. This suggests that the HPV in blood is attached to the outside of blood cells via a protein-containing moiety. HPV was also isolated in the B cells, dendritic cells, NK cells, and neutrophils. To conclude, HPV present in PBMCs could represent a reservoir of virus and a potential new route of transmission.

Estimating the cost of health care–associated infections : mind your p’s and q’s

Monetary valuations of the economic cost of health care–associated infections (HAIs) are important for decision making and should be estimated accurately. Erroneously high estimates of costs, designed to jolt decision makers into action, may do more harm than good in the struggle to attract funding for infection control. Expectations among policy makers might be raised, and then they are disappointed when the reduction in the number of HAIs does not yield the anticipated cost saving. For this article, we critically review the field and discuss 3 questions. Why measure the cost of an HAI? What outcome should be used to measure the cost of an HAI? What is the best method for making this measurement? The aim is to encourage researchers to collect and then disseminate information that accurately guides decisions about the economic value of expanding or changing current infection control activities.

Time-dependent analysis of length of stay and mortality due urinary tract infections in ten developing countries : INICC findings

Catheter associated urinary tract infections (CAUTI) are a worldwide problem that may lead to increased patient morbidity, cost and mortality.1e3 The literature is divided on whether there are real effects from CAUTI on length of stay or mortality. Platt4 found the costs and mortality risks to be largeyetGraves et al found the opposite.5 A reviewof the published estimates of the extra length of stay showed results between zero and 30 days.6 The differences in estimates may have been caused by the different epidemiological methods applied. Accurately estimating the effects of CAUTI is difficult because it is a time-dependent exposure. This means that standard statistical techniques, such asmatched case-control studies, tend to overestimate the increased hospital stay and mortality risk due to infection. The aim of the study was to estimate excess length of stay andmortality in an intensive care unit (ICU) due to a CAUTI, using a statistical model that accounts for the timing of infection. Data collected from ICU units in lower and middle income countries were used for this analysis.7,8 There has been little research for these settings, hence the need for this paper.

Spatial analysis of notified dengue fever infections

This study aimed to investigate the spatial clustering and dynamic dispersion of dengue incidence in Queensland, Australia. We used Moran’s I statistic to assess the spatial autocorrelation of reported dengue cases. Spatial empirical Bayes smoothing estimates were used to display the spatial distribution of dengue in postal areas throughout Queensland. Local indicators of spatial association (LISA) maps and logistic regression models were used to identify spatial clusters and examine the spatio-temporal patterns of the spread of dengue. The results indicate that the spatial distribution of dengue was clustered during each of the three periods of 1993–1996, 1997–2000 and 2001–2004. The high-incidence clusters of dengue were primarily concentrated in the north of Queensland and low-incidence clusters occurred in the south-east of Queensland. The study concludes that the geographical range of notified dengue cases has significantly expanded in Queensland over recent years.

Identification of novel markers for uncomplicated lower genital tract infections and upper genital tract pathology due to Chlamydia trachomatis.

Background: Untreated Chlamydia trachomatis infections in women can result in disease sequelae such as salpingitis and pelvic inflammatory disease (PID), ultimately culminating in tubal occlusion and infertility. Whilst nucleic acid amplification tests can effectively diagnose uncomplicated lower genital tract (LGT) infections, they are not suitable for diagnosing upper genital tract (UGT) pathological sequelae. As a consequence, this study aimed to identify serological markers that can, with a high degree of sensitivity and specificity, discriminate between LGT infections and UGT pathology. Methods: Plasma was collected from 73 women with a history of LGT infection, UGT pathology due to C. trachomatis or no serological evidence of C. trachomatis infection. Western blotting was used to analyse antibody reactivity against extracted chlamydial proteins. Sensitivity and specificity of differential markers were also calculated. Results: Four antigens (CT157, CT423, CT727 and CT396) were identified and found to be capable of discriminating between the infection and disease sequelae state. Sensitivity and specificity calculations showed that our assay for diagnosing LGT infection had a sensitivity and specificity of 75% and 76% respectively, whilst the assay for identifying UGT pathology demonstrated 80% sensitivity and 86% specificity. Conclusions: The use of these assays could potentially facilitate earlier diagnoses in women suffering UGT pathology due to C. trachomatis.

Defective interfering viral particles in acute dengue infections

While much of the genetic variation in RNA viruses arises because of the error-prone nature of their RNA-dependent RNA polymerases, much larger changes may occur as a result of recombination. An extreme example of genetic change is found in defective interfering (DI) viral particles, where large sections of the genome of a parental virus have been deleted and the residual sub-genome fragment is replicated by complementation by co-infecting functional viruses. While most reports of DI particles have referred to studies in vitro, there is some evidence for the presence of DI particles in chronic viral infections in vivo. In this study, short fragments of dengue virus (DENV) RNA containing only key regulatory elements at the 3' and 5' ends of the genome were recovered from the sera of patients infected with any of the four DENV serotypes. Identical RNA fragments were detected in the supernatant from cultures of Aedes mosquito cells that were infected by the addition of sera from dengue patients, suggesting that the sub-genomic RNA might be transmitted between human and mosquito hosts in defective interfering (DI) viral particles. In vitro transcribed sub-genomic RNA corresponding to that detected in vivo could be packaged in virus like particles in the presence of wild type virus and transmitted for at least three passages in cell culture. DENV preparations enriched for these putative DI particles reduced the yield of wild type dengue virus following co-infections of C6-36 cells. This is the first report of DI particles in an acute arboviral infection in nature. The internal genomic deletions described here are the most extensive defects observed in DENV and may be part of a much broader disease attenuating process that is mediated by defective viruses.

Ovarian steroid hormones: effects on immune responses and Chlamydia trachomatis infections of the female genital tract

Female sex hormones are known to regulate the adaptive and innate immune functions of the female reproductive tract. This review aims to update our current knowledge of the effects of the sex hormones estradiol and progesterone in the female reproductive tract on innate immunity, antigen presentation, specific immune responses, antibody secretion, genital tract infections caused by Chlamydia trachomatis, and vaccine-induced immunity.