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.

Impact of Wolbachia on infection with chikungunya and yellow fever viruses in the mosquito vector Aedes aegypti

Incidence of disease due to dengue (DENV), chikungunya (CHIKV) and yellow fever (YFV) viruses is increasing in many parts of the world. The viruses are primarily transmitted by Aedes aegypti, a highly domesticated mosquito species that is notoriously difficult to control. When transinfected into Ae. aegypti, the intracellular bacterium Wolbachia has recently been shown to inhibit replication of DENVs, CHIKV, malaria parasites and filarial nematodes, providing a potentially powerful biocontrol strategy for human pathogens. Because the extent of pathogen reduction can be influenced by the strain of bacterium, we examined whether the wMel strain of Wolbachia influenced CHIKV and YFV infection in Ae. aegypti. Following exposure to viremic blood meals, CHIKV infection and dissemination rates were significantly reduced in mosquitoes with the wMel strain of Wolbachia compared to Wolbachia-uninfected controls. However, similar rates of infection and dissemination were observed in wMel infected and non-infected Ae. aegypti when intrathoracic inoculation was used to deliver virus. YFV infection, dissemination and replication were similar in wMel-infected and control mosquitoes following intrathoracic inoculations. In contrast, mosquitoes with the wMelPop strain of Wolbachia showed at least a 10(4) times reduction in YFV RNA copies compared to controls. The extent of reduction in virus infection depended on Wolbachia strain, titer and strain of the virus, and mode of exposure. Although originally proposed for dengue biocontrol, our results indicate a Wolbachia-based strategy also holds considerable promise for YFV and CHIKV suppression.

Dengue fever viral exposure rates among blood donors during outbreaks in North Queensland

Introduction: Dengue poses a problem for safe transfusion of blood components with confirmed reports of transfusion-transmission in Hong Kong and Singapore. The largest outbreak in 50 years occurred in North Queensland during 2008/2009 with more than 1,000 confirmed cases in Cairns and Townsville. During this outbreak, supplementary questioning for all donors was implemented, and fresh components were not manufactured from at risk donors. We aim to determine the seroprevalence of dengue exposure in this population during this epidemic. Methods: Samples were collected from blood donors during the 2008/2009 epidemic and 3 months after the last confirmed case. These samples were tested for anti-Dengue IgM, IgG and NS1 antigen with commercially available ELISA based assay kits from PanBio. Results: Initial analyses revealed 2.7% of samples from deferred donors were IgM repeat reactive. Of these, 16% were also positive for anti-dengue IgG, while none of these were positive for the NS1 viral antigen. However, two NS1 positives were found in samples collected from deferred donors. Conclusions: This initial analysis represents recent and cumulative past exposure in a presumed asymptomatic population, and will provide documentation of the rate of asymptomatic dengue infection during the epidemic. This data can also be used to assess the risk of dengue becoming endemic in North Queensland given that the mosquito vector is established in this region.

Tangled Webs : Using Bayesian Networks in the Fight Against Infection

Bayesian networks (BNs) provide a statistical modelling framework which is ideally suited for modelling the many factors and components of complex problems such as healthcare-acquired infections. The methicillin-resistant Staphylococcus aureus (MRSA) organism is particularly troublesome since it is resistant to standard treatments for Staph infections. Overcrowding and understa�ng are believed to increase infection transmission rates and also to inhibit the effectiveness of disease control measures. Clearly the mechanisms behind MRSA transmission and containment are very complicated and control strategies may only be e�ective when used in combination. BNs are growing in popularity in general and in medical sciences in particular. A recent Current Content search of the number of published BN journal articles showed a fi�ve fold increase in general and a six fold increase in medical and veterinary science from 2000 to 2009. This chapter introduces the reader to Bayesian network (BN) modelling and an iterative modelling approach to build and test the BN created to investigate the possible role of high bed occupancy on transmission of MRSA while simultaneously taking into account other risk factors.

Increased risk of hospitalization for acute lower respiratory tract infection among Australian Indigenous infants 5-23 months of age following pneumococcal vaccination : a cohort study

Background Australian Indigenous children are the only population worldwide to receive the 7-valent pneumococcal conjugate vaccine (7vPCV) at 2, 4, and 6 months of age and the 23-valent pneumococcal polysaccharide vaccine (23vPPV) at 18 months of age. We evaluated this program's effectiveness in reducing the risk of hospitalization for acute lower respiratory tract infection (ALRI) in Northern Territory (NT) Indigenous children aged 5-23 months. Methods We conducted a retrospective cohort study involving all NT Indigenous children born from 1 April 2000 through 31 October 2004. Person-time at-risk after 0, 1, 2, and 3 doses of 7vPCV and after 0 and 1 dose of 23vPPV and the number of ALRI following each dose were used to calculate dose-specific rates of ALRI for children 5-23 months of age. Rates were compared using Cox proportional hazards models, with the number of doses of each vaccine serving as time-dependent covariates. Results There were 5482 children and 8315 child-years at risk, with 2174 episodes of ALRI requiring hospitalization (overall incidence, 261 episodes per 1000 child-years at risk). Elevated risk of ALRI requiring hospitalization was observed after each dose of the 7vPCV vaccine, compared with that for children who received no doses, and an even greater elevation in risk was observed after each dose of the 23vPPV ( adjusted hazard ratio [HR] vs no dose, 1.39; 95% confidence interval [CI], 1.12-1.71;). Risk was highest among children Pp. 002 vaccinated with the 23vPPV who had received < 3 doses of the 7vPCV (adjusted HR, 1.81; 95% CI, 1.32-2.48). Conclusions Our results suggest an increased risk of ALRI requiring hospitalization after pneumococcal vaccination, particularly after receipt of the 23vPPV booster. The use of the 23vPPV booster should be reevaluated.

Management of periprosthetic joint infection after total hip arthroplasty using a Custom Made Articulating Spacer (CUMARS); the exeter experience

Periprosthetic joint infection (PJI) after THA is a major complication with an incidence of 1-3%. We report our experiences with a technique using a custom-made articulating spacer (CUMARS) at the first of two-stage treatment for PJI. This technique uses widely available all-polyethylene acetabular components and the Exeter Universal stem, fixed using antibiotic loaded acrylic cement. Seventy-six hips were treated for PJI using this technique. Performed as the first of a two-stage procedure, good functional results were commonly seen, leading to postponing second stage indefinitely with retention of the CUMARS prosthesis in 34 patients. The CUMARS technique presents an alternative to conventional spacers, using readily available components that are well tolerated, allowing weight bearing and mobility, and achieving comparable eradication rates.

The importance of good data, analysis and interpretation for showing the economics of reducing healthcare-associated infection

To the Editor—In a recent review article in Infection Control and Hospital Epidemiology, Umscheid et al1 summarized published data on incidence rates of catheter-associated bloodstream infection (CABSI), catheter-associated urinary tract infection (CAUTI), surgical site infection (SSI), and ventilator- associated pneumonia (VAP); estimated how many cases are preventable; and calculated the savings in hospital costs and lives that would result from preventing all preventable cases. Providing these estimates to policy makers, political leaders, and health officials helps to galvanize their support for infection prevention programs. Our concern is that important limitations of the published studies on which Umscheid and colleagues built their findings are incompletely addressed in this review. More attention needs to be drawn to the techniques applied to generate these estimates...

Multilevel competing risk models to evaluate the risk of nosocomial infection

Introduction Risk factor analyses for nosocomial infections (NIs) are complex. First, due to competing events for NI, the association between risk factors of NI as measured using hazard rates may not coincide with the association using cumulative probability (risk). Second, patients from the same intensive care unit (ICU) who share the same environmental exposure are likely to be more similar with regard to risk factors predisposing to a NI than patients from different ICUs. We aimed to develop an analytical approach to account for both features and to use it to evaluate associations between patient- and ICU-level characteristics with both rates of NI and competing risks and with the cumulative probability of infection. Methods We considered a multicenter database of 159 intensive care units containing 109,216 admissions (813,739 admission-days) from the Spanish HELICS-ENVIN ICU network. We analyzed the data using two models: an etiologic model (rate based) and a predictive model (risk based). In both models, random effects (shared frailties) were introduced to assess heterogeneity. Death and discharge without NI are treated as competing events for NI. Results There was a large heterogeneity across ICUs in NI hazard rates, which remained after accounting for multilevel risk factors, meaning that there are remaining unobserved ICU-specific factors that influence NI occurrence. Heterogeneity across ICUs in terms of cumulative probability of NI was even more pronounced. Several risk factors had markedly different associations in the rate-based and risk-based models. For some, the associations differed in magnitude. For example, high Acute Physiology and Chronic Health Evaluation II (APACHE II) scores were associated with modest increases in the rate of nosocomial bacteremia, but large increases in the risk. Others differed in sign, for example respiratory vs cardiovascular diagnostic categories were associated with a reduced rate of nosocomial bacteremia, but an increased risk. Conclusions A combination of competing risks and multilevel models is required to understand direct and indirect risk factors for NI and distinguish patient-level from ICU-level factors.

Evidence for a simple linear relationship between MRSA rates and hand-washing compliance [Comment]

Is there a threshold above which hand-rub solution consumption is efficient for decreasing MRSA incidence? [J Hosp Infect. 2009] Association between an index of consumption of hand-rub solution and the incidence of acquired meticillin-resistant Staphylococcus aureus in an intensive care unit.

Cytomegalovirus infection after liver transplantation in children

Post-liver transplant cytomegalovirus (CMV) infection (seroconversion or virus isolation) and CMV disease (infection plus clinical signs and symptoms) were studied in relation to pretransplant recipient and donor serology, age, nutritional status and the effect of paediatric versus adult (reduced size) grafts. Of 70 children receiving 79 transplants, 26 (37%) had evidence of CMV infection, and eight (11.5%) had evidence of CMV disease, four of whom died. The primary infection rate (where the recipients were CMV negative) was 71% with mortality of 7% with most receiving a CMV-positive graft. The active secondary infection rate (reactivation or reinfection, where the recipients were CMV positive) was 60% with mortality of 12.5%. No significant differences in infection on disease rates were found comparing malnourished versus well-nourished patients, or between those who received whole or reduced-size grafts. The high prevalence of CMV infections supports the view that clinical signs alone are inadequate to direct investigations for CMV. Both primary and active secondary CMV infection can result in serious morbidity and mortality in children receiving liver transplants. These data do not support the strategy of providing immunoprophylaxis to seronegative recipients only, at least in paediatric liver transplantation.

Dengue virus infection : Diagnostics and molecular epidemiology

Dengue is a mosquito-borne viral disease caused by the four dengue virus serotypes (DENV-1-4) and is currently considered as the most important arthropod-borne viral disease in the world. Nearly half of the human population lives in risk areas, and 50-100 million infections occur yearly according to World Health Organization. The disease can vary from a mild febrile disease to severe haemorrhagic fever and shock. A secondary infection with heterologous serotype increases the risk for severe disease outcome. During the last three decades the impact of dengue has dramatically increased in the endemic areas including the tropics and subtropics of the world. The current situation with massive epidemics of severe disease forms has been associated with socio-ecological changes that have increased the transmission and enabled the co-circulation of different serotypes. Consequently, an increase of dengue has also been observed in travelers visiting these areas. Currently approximately 30 cases are diagnosed yearly in Finnish travelers. In travelers dengue is rarely a life-threatening disease, however in the current study, a fatality was documented in a young Finnish patient who experienced a prolonged primary dengue infection. To improve particularly early laboratory diagnostics, a novel real-time RT-PCR method was developed for the detection of DENV-1-4 RNA based on TaqMan chemistry. The method was shown to be sensitive and specific for detecting DENV RNA and suitable for diagnostic use. The newly developed real-time RT-PCR was compared to other available early diagnostic methods including IgM and NS1 antigen detection using a panel of selected patient samples. The results suggest that the best diagnostic rates are achieved by a combination of IgM with RNA or NS1 detection. The dengue virus strains studied here included the first DENV strains isolated from serum samples of Finnish travelers collected in 2000-2005. The results of sequence analysis demonstrated that the 11 isolates included all four DENV serotypes and presented a global sample of DENV strains from different geographical areas including Asia, Africa and South America. In the present study sequence analysis was also carried out for a collection of 23 novel DENV-2 isolates from Venezuelan patients collected in 1999-2005. The Venezuelan DENV-2 exclusively represented the American-Asian genotype, suggesting that no foreign DENV-2 lineages have recently been introduced to the country. The results also suggest that the DENV-2 viruses detected earlier from Venezuela have been maintained in the area where they have evolved into several lineages. This is in contrast to the pattern observed in some other dengue endemic areas, where introductions of novel virus types and lineages are frequently detected.

Symptom development proceeds at different rates in susceptible and partially resistant cereal seedlings infected with Fusarium pseudograminearum

Variation in the reaction of cereal cultivars to crown rot caused by Fusarium spp., in particular Fusarium pseudograminearum, was identified over 50 yrs ago, however the parameters and pathways of infection by F. pseudograminearum remain poorly understood. Seedlings of wheat, barley and oat genotypes that differ in susceptibility to crown rot were inoculated with a mixture of F. pseudograminearum isolates. Seedlings were harvested from 7 to 42 days after inoculation and expanded plant parts were rated for severity of visible disease symptoms. Individual leaf sheaths were placed onto nutrient media and fungal colonies emerging from the leaf sheathes were counted to estimate the degree of fungal spread within the host tissue. Significant differences in both the timing and the severity of disease symptoms were observed in the leaf sheath tissues of different host genotypes. Across all genotypes and plant parts examined, the development of visible symptoms closely correlated with the spread of the fungus into that tissue. The degree of infection of the coleoptile and sub-crown internode varied between genotypes, but was unrelated to the putative resistance of the host. In contrast leaf sheath tissues of the susceptible barley cv. Tallon and bread wheat cv. Puseas scored higher disease ratings and consistently showed faster, earlier spread of the fungus into younger tissues than infections of the oat cv. Cleanleaf or the wheat lines 2-49 and CPI 133814. While initial infections usually spread upwards from near the base of the first leaf sheath, the pathogen did not appear to invade younger leaf sheaths only from the base, but rather spread laterally across from older leaf sheaths into younger, subtended leaf sheaths, particularly as disease progressed. Early in the infection of each leaf sheath, disease symptoms in the partially resistant genotypes were less severe than in susceptible genotypes, however as infected leaf sheaths aged, differences between genotypes lessened as disease symptoms approached maximum values. Hence, while visual scoring of disease symptoms on leaf sheaths is a reliable comparative measure of the degree of fungal infection, differences between genotypes in the development of disease symptoms are more reliably assessed using the most recently expanded leaf sheaths.

Evaluation of ELISA coupled with Western blot as a surveillance tool for Trichinella infection in wild boar (Sus scrofa)

Trichinella surveillance in wildlife relies on muscle digestion of large samples which are logistically difficult to store and transport in remote and tropical regions as well as labour-intensive to process. Serological methods such as enzyme-linked immunosorbent assays (ELISAs) offer rapid, cost-effective alternatives for surveillance but should be paired with additional tests because of the high false-positive rates encountered in wildlife. We investigated the utility of ELISAs coupled with Western blot (WB) in providing evidence of Trichinella exposure or infection in wild boar. Serum samples were collected from 673 wild boar from a high- and low-risk region for Trichinella introduction within mainland Australia, which is considered Trichinella-free. Sera were examined using both an 'in-house' and a commercially available indirect-ELISA that used excretory secretory (E/S) antigens. Cut-off values for positive results were determined using sera from the low-risk population. All wild boar from the high-risk region (352) and 139/321 (43.3%) of the wild boar from the low-risk region were tested by artificial digestion. Testing by Western blot using E/S antigens, and a Trichinella-specific real-time PCR was also carried out on all ELISA-positive samples. The two ELISAs correctly classified all positive controls as well as one naturally infected wild boar from Gabba Island in the Torres Strait. In both the high- and low-risk populations, the ELISA results showed substantial agreement (k-value = 0.66) that increased to very good (k-value = 0.82) when WB-positive only samples were compared. The results of testing sera collected from the Australian mainland showed the Trichinella seroprevalence was 3.5% (95% C.I. 0.0-8.0) and 2.3% (95% C.I. 0.0-5.6) using the in-house and commercial ELISA coupled with WB respectively. These estimates were significantly higher (P < 0.05) than the artificial digestion estimate of 0.0% (95% C.I. 0.0-1.1). Real-time PCR testing of muscle from seropositive animals did not detect Trichinella DNA in any mainland animals, but did reveal the presence of a second larvae-positive wild boar on Gabba Island, supporting its utility as an alternative, highly sensitive method in muscle examination. The serology results suggest Australian wildlife may have been exposed to Trichinella parasites. However, because of the possibility of non-specific reactions with other parasitic infections, more work using well-defined cohorts of positive and negative samples is required. Even if the specificity of the ELISAs is proven to be low, their ability to correctly classify the small number of true positive sera in this study indicates utility in screening wild boar populations for reactive sera which can be followed up with additional testing. (C) 2013 Elsevier B.V. All rights reserved.

The non-pathogenic Australian rabbit calicivirus RCV-A1 provides temporal and partial cross protection to lethal Rabbit Haemorrhagic Disease Virus infection which is not dependent on antibody titres

The endemic non-pathogenic Australian rabbit calicivirus RCV-A1 is known to provide some cross protection to lethal infection with the closely related Rabbit Haemorrhagic Disease Virus (RHDV). Despite its obvious negative impacts on viral biocontrol of introduced European rabbits in Australia, little is known about the extent and mechanisms of this cross protection. In this study 46 rabbits from a colony naturally infected with RCV-A1 were exposed to RHDV. Survival rates and survival times did not correlate with titres of serum antibodies specific to RCV-A1 or cross reacting to RHDV, but were instead influenced by the time between infection with the two viruses, demonstrating for the first time that the cross protection to lethal RHDV infection is transient. These findings are an important step towards a better understanding of the complex interactions of co-occurring pathogenic and non-pathogenic lagoviruses.

Potential Animal and Environmental Sources of Q Fever Infection for Humans in Queensland

Q fever is a vaccine-preventable disease; despite this, high annual notification numbers are still recorded in Australia. We have previously shown seroprevalence in Queensland metropolitan regions is approaching that of rural areas. This study investigated the presence of nucleic acid from Coxiella burnetii, the agent responsible for Q fever, in a number of animal and environmental samples collected throughout Queensland, to identify potential sources of human infection. Samples were collected from 129 geographical locations and included urine, faeces and whole blood from 22 different animal species; 45 ticks were removed from two species, canines and possums; 151 soil samples; 72 atmospheric dust samples collected from two locations and 50 dust swabs collected from domestic vacuum cleaners. PCR testing was performed targeting the IS1111 and COM1 genes for the specific detection of C.burnetii DNA. There were 85 detections from 1318 animal samples, giving a detection rate for each sample type ranging from 2.1 to 6.8%. Equine samples produced a detection rate of 11.9%, whilst feline and canine samples showed detection rates of 7.8% and 5.2%, respectively. Native animals had varying detection rates: pooled urines from flying foxes had 7.8%, whilst koalas had 5.1%, and 6.7% of ticks screened were positive. The soil and dust samples showed the presence of C.burnetii DNA ranging from 2.0 to 6.9%, respectively. These data show that specimens from a variety of animal species and the general environment provide a number of potential sources for C.burnetii infections of humans living in Queensland. These previously unrecognized sources may account for the high seroprevalence rates seen in putative low-risk communities, including Q fever patients with no direct animal contact and those subjects living in a low-risk urban environment.