Effectiveness of portable air filtration on reducing indoor aerosol transmission: preclinical observational trials.

BACKGROUND: While the range of possible transmission pathways of severe acute respiratory syndrome coronavirus-2 in various settings has been investigated thoroughly, most authorities have recently acknowledged the role of aerosol spread in its transmission, especially in indoor environments where ventilation is poor. Engineering controls are needed to mitigate aerosol transmission in high-risk settings including hospital wards, classrooms and offices. AIM: To assess the effectiveness of aerosol filtration by portable air cleaning devices with high-efficiency particulate air filters used in addition to a standard building heating ventilation and air conditioning (HVAC) system. METHODS: Test rooms, including a single-bed hospital room, were filled with test aerosol to simulate aerosol movement. Aerosol counts were measured over time with various portable air cleaning devices and room ventilation systems to quantify the overall aerosol clearance rate. FINDINGS: Portable air cleaning devices were very effective for removal of aerosols. The aerosols were cleared five times faster in a small control room with portable air cleaning devices than in the room with HVAC alone. The single-bed hospital room had an excellent ventilation rate (∼14 air changes per hour) and cleared the aerosols in 20 min. However, with the addition of two air cleaning devices, the clearance time was three times faster. CONCLUSIONS: Inexpensive portable air cleaning devices should be considered for small and enclosed spaces in healthcare settings, such as inpatient rooms and personal protective equipment donning/doffing stations. Portable air cleaning devices are particularly important where there is limited ability to reduce aerosol transmission with building HVAC ventilation.

Introducing antigen-binding sites in structural loops of immunoglobulin constant domains: Fc fragments with engineered HER2/neu-binding sites and antibody properties.

Yeast surface display libraries of human IgG1 Fc regions were prepared in which loop sequences at the C-terminal tip of the CH3 domain were randomized. A high percentage of these library members bound to soluble CD64 and Protein A indicating that the randomization step did not grossly interfere with the overall structure of the displayed Fc. Sorting these libraries by FACS for binders against HER2/neu yielded antigen-specific Fc binders (Fcab; Fc antigen binding) of which one was affinity matured, resulting in Fcab clone H10-03-6 which showed >10-fold improvement in antigen-binding activity versus the parental clone. Pre-equilibrium surface plasmon resonance experiments revealed a K(D) value of 69 nM. H10-03-6 did not react with other members of the HER family and specifically interacted with HER2-positive but not with HER2-negative cells. Importantly, Fcab H10-03-6 elicited potent antibody-dependent cellular cytotoxicity in vitro. Finally, the in vivo half-life in mice was similar to wild-type Fc indicating that the amino acid changes in the CH3 domain did not affect the pharmacokinetic behavior of the recombinant Fc. Our data demonstrate that the Fcab scaffold combines all features of normal antibodies in a small 50 kD homodimeric protein: antigen binding, effector functions and long half-life in vivo.

Successful use of rifampicin for Hispanic foreign-born patients with latent tuberculosis infection.

SETTING: Four months of rifampicin (4R) is recommended for the treatment of latent tuberculosis infection (LTBI), although data regarding its use are limited. The majority of tuberculosis (TB) cases in the USA occur among foreign-born persons. OBJECTIVE: To determine tolerability, hepatotoxicity and completion rates associated with 4R among foreign-born persons. DESIGN: We retrospectively evaluated 4R treatment among a cohort of predominantly Hispanic foreign-born LTBI patients in four Middle-Tennessee public health clinics from February 2000 to February 2004. Patients' charts were reviewed to abstract demographic, social and clinical data. 4R completion rates, new symptoms and hepatotoxicity (serum aminoalanine transferase >or=120U/l with gastrointestinal symptoms or >or=200 regardless of symptoms) were evaluated. RESULTS: Of 749 patients treated, 571 (76%) completed 4R. Among all subjects, Hispanics had a lower risk of non-completion (OR 0.6, 95%CI 0.4-0.7) than non-Hispanics. Among non-Hispanic subjects, the risk of non-completion was higher for Blacks than non-Blacks (adjusted OR 2.6, 95%CI 1.5-4.7), but was lower for foreign-born than non-foreign-born subjects (adjusted OR 0.5, 95%CI 0.2-0.9). During treatment, 85 subjects (11%) developed new symptoms, and hepatotoxicity occurred in three patients. CONCLUSION: With high completion rates and minimal side effects, 4R is a favorable LTBI treatment regimen for Hispanic and other foreign-born patients.

Biological weapons preparedness: the role of physicians.

The real risk posed by biological weapons was demonstrated with the distribution of anthrax spores via the USA postal service in 2001. This review outlines the central roles of physicians in optimizing biopreparedness in Australia, including maintaining awareness of the risk, promptly recognizing an event, notifying appropriate authorities upon suspicion of an event, and instituting appropriate management. Management aspects covered include appropriate diagnostic tests, infection control procedures, and empirical therapy of agents considered possible biological weapons. The critical role of physicians as public health advocates working to prevent the use of biological weapons is also outlined.

A randomised, clinical trial comparing the effectiveness of hospital and community-based reminder systems for increasing uptake of influenza and pneumococcal vaccine in hospitalised patients aged 65 years and over.

Hospitalisation represents an opportunity to identify unimmunised people at risk for the complications of influenza and pneumococcal disease. We conducted a randomised controlled trial of two strategies to increase uptake of influenza and pneumococcal vaccines in eligible, hospitalised subjects aged 65 years or more, admitted between May and September 1998 to a Melbourne hospital. Unvaccinated participants were allocated randomly to alert systems for hospital staff or community general practitioners (GPs). Follow-up occurred at 1 and 3 months. The baseline vaccination rates were 70% for influenza (426/606) and 41% (248/606) for pneumococcal disease. For unvaccinated subjects, the hospital alert resulted in 67% uptake compared to 55% following a GP alert for pneumococcal vaccine; and 63% in hospital compared to 53% following a GP alert for influenza vaccine. Although there was a trend toward a higher uptake in hospital, neither of these differences was statistically significant. The majority (75%) of vaccinations following a GP alert occurred within 1 month of discharge. Despite hospital and community-based reminder systems, there are still significant missed opportunities for vaccination. We did not demonstrate significant differences between hospital and GP reminder systems, but there was a trend towards higher uptake with opportunistic vaccination in hospital.

Investigation of potential iatrogenic transmission of hepatitis C in Victoria, Australia.

OBJECTIVE: To determine the level of exposure to medical and surgical procedures among Australian-born patients whose mode of acquisition of the hepatitis C virus (HCV) is unknown. METHOD: Place and time of study: Melbourne, Australia, 1998-2000. DESIGN: Retrospective case series. INSTRUMENT: Structured questionnaire administered by one interviewer. SETTING: Referral centre for hepatitis C in a tertiary teaching hospital. PARTICIPANTS: Australian-born individuals persistently HCV antibody (anti-HCV) positive on at least two second-generation commercial assays. MAIN OUTCOME MEASURES: Demographic and self-reported exposure data. RESULTS: Of 135 anti-HCV positive individuals with no known mode of transmission, 54 (40%) individuals fulfilled all the entry criteria and agreed to participate. Of the 54 cases, 53 had at least one medical/surgical procedure and/or invasive dental work; 46 (85%) had dental extractions, 19 (35.2%) had complex dental work, e.g. root canal, 44 (82%) had an operation requiring general anaesthesia, 41 (75.9%) had a procedure requiring local anaesthetic, and a number of endoscopic procedures were reported: gastroscopy (n=3), colonoscopy (n=3), laparoscopy (n=4), arthroscopy (n=5), cystoscopy (n=2). CONCLUSION: We have documented exposure to medica/surgical procedures among HCV patients with no previously recognised mode of transmission. IMPLICATIONS: The findings of this study have important public health implications for current cleaning, disinfection and sterilisation procedures and protocols (or lack of these) as well as for the policies and guidelines relating to the re-use of medical equipment such as multi-dose vials, suturing material and anaesthetic circuits.

Treatment of herpes simplex and varicella zoster infections.

The introduction of antiviral agents such as acyclovir has had a remarkable impact on management of patients with viral infections. In this article the authors outline the management of herpes simplex and varicella zoster infections, giving specific guidelines for treatment with acyclovir.