Catherine J. Noakes

The Infectiousness of Tuberculosis Patients Coinfected with HIV

Background The current understanding of airborne tuberculosis (TB) transmission is based on classic 1950s studies in which guinea pigs were exposed to air from a tuberculosis ward. Recently we recreated this model in Lima, Perú, and in this paper we report the use of molecular fingerprinting to investigate patient infectiousness in the current era of HIV infection and multidrug-resistant (MDR) TB. Methods and Findings All air from a mechanically ventilated negative-pressure HIV-TB ward was exhausted over guinea pigs housed in an airborne transmission study facility on the roof. Animals had monthly tuberculin skin tests, and positive reactors were removed for autopsy and organ culture for M. tuberculosis. Temporal exposure patterns, drug susceptibility testing, and DNA fingerprinting of patient and animal TB strains defined infectious TB patients. Relative patient infectiousness was calculated using the Wells-Riley model of airborne infection. Over 505 study days there were 118 ward admissions of 97 HIV-positive pulmonary TB patients. Of 292 exposed guinea pigs, 144 had evidence of TB disease; a further 30 were tuberculin skin test positive only. There was marked variability in patient infectiousness; only 8.5% of 118 ward admissions by TB patients were shown by DNA fingerprinting to have caused 98% of the 125 characterised cases of secondary animal TB. 90% of TB transmission occurred from inadequately treated MDR TB patients. Three highly infectious MDR TB patients produced 226, 52, and 40 airborne infectious units (quanta) per hour. Conclusions A small number of inadequately treated MDR TB patients coinfected with HIV were responsible for almost all TB transmission, and some patients were highly infectious. This result highlights the importance of rapid TB drug-susceptibility testing to allow prompt initiation of effective treatment, and environmental control measures to reduce ongoing TB transmission in crowded health care settings. TB infection control must be prioritized in order to prevent health care facilities from disseminating the drug-resistant TB that they are attempting to treat.

Upper-Room Ultraviolet Light and Negative Air Ionization to Prevent Tuberculosis Transmission

Background Institutional tuberculosis (TB) transmission is an important public health problem highlighted by the HIV/AIDS pandemic and the emergence of multidrug- and extensively drug-resistant TB. Effective TB infection control measures are urgently needed. We evaluated the efficacy of upper-room ultraviolet (UV) lights and negative air ionization for preventing airborne TB transmission using a guinea pig air-sampling model to measure the TB infectiousness of ward air. Methods and Findings For 535 consecutive days, exhaust air from an HIV-TB ward in Lima, Perú, was passed through three guinea pig air-sampling enclosures each housing approximately 150 guinea pigs, using a 2-d cycle. On UV-off days, ward air passed in parallel through a control animal enclosure and a similar enclosure containing negative ionizers. On UV-on days, UV lights and mixing fans were turned on in the ward, and a third animal enclosure alone received ward air. TB infection in guinea pigs was defined by monthly tuberculin skin tests. All guinea pigs underwent autopsy to test for TB disease, defined by characteristic autopsy changes or by the culture of Mycobacterium tuberculosis from organs. 35% (106/304) of guinea pigs in the control group developed TB infection, and this was reduced to 14% (43/303) by ionizers, and to 9.5% (29/307) by UV lights (both p < 0.0001 compared with the control group). TB disease was confirmed in 8.6% (26/304) of control group animals, and this was reduced to 4.3% (13/303) by ionizers, and to 3.6% (11/307) by UV lights (both p < 0.03 compared with the control group). Time-to-event analysis demonstrated that TB infection was prevented by ionizers (log-rank 27; p < 0.0001) and by UV lights (log-rank 46; p < 0.0001). Time-to-event analysis also demonstrated that TB disease was prevented by ionizers (log-rank 3.7; p = 0.055) and by UV lights (log-rank 5.4; p = 0.02). An alternative analysis using an airborne infection model demonstrated that ionizers prevented 60% of TB infection and 51% of TB disease, and that UV lights prevented 70% of TB infection and 54% of TB disease. In all analysis strategies, UV lights tended to be more protective than ionizers. Conclusions Upper-room UV lights and negative air ionization each prevented most airborne TB transmission detectable by guinea pig air sampling. Provided there is adequate mixing of room air, upper-room UV light is an effective, low-cost intervention for use in TB infection control in high-risk clinical settings.

The detection of airborne transmission of tuberculosis from HIV-infected patients, using an in vivo air sampling model.

BACKGROUND Nosocomial transmission of tuberculosis remains an important public health problem. We created an in vivo air sampling model to study airborne transmission of tuberculosis from patients coinfected with human immunodeficiency virus (HIV) and to evaluate environmental control measures. METHODS An animal facility was built above a mechanically ventilated HIV-tuberculosis ward in Lima, Peru. A mean of 92 guinea pigs were continuously exposed to all ward exhaust air for 16 months. Animals had tuberculin skin tests performed at monthly intervals, and those with positive reactions were removed for autopsy and culture for tuberculosis. RESULTS Over 505 consecutive days, there were 118 ward admissions by 97 patients with pulmonary tuberculosis, with a median duration of hospitalization of 11 days. All patients were infected with HIV and constituted a heterogeneous group with both new and existing diagnoses of tuberculosis. There was a wide variation in monthly rates of guinea pigs developing positive tuberculin test results (0%-53%). Of 292 animals exposed to ward air, 159 developed positive tuberculin skin test results, of which 129 had laboratory confirmation of tuberculosis. The HIV-positive patients with pulmonary tuberculosis produced a mean of 8.2 infectious quanta per hour, compared with 1.25 for HIV-negative patients with tuberculosis in similar studies from the 1950s. The mean monthly patient infectiousness varied greatly, from production of 0-44 infectious quanta per hour, as did the theoretical risk for a health care worker to acquire tuberculosis by breathing ward air. CONCLUSIONS HIV-positive patients with tuberculosis varied greatly in their infectiousness, and some were highly infectious. Use of environmental control strategies for nosocomial tuberculosis is therefore a priority, especially in areas with a high prevalence of both tuberculosis and HIV infection.

The ventilation of multiple-bed hospital wards: review and analysis.

BACKGROUND Although the merits of ventilating operating theatres and isolation rooms are well known, the clinical benefits derived from ventilating hospital wards and patient rooms are unclear. This is because relatively little research work has been done in the ventilation of these areas compared with that done in operating theatres and isolation rooms. Consequently, there is a paucity of good quality data from which to make important decisions regarding hospital infrastructure. This review evaluates the role of general ward ventilation to assess whether or not it affects the transmission of infection. METHODS A critical review was undertaken of guidelines in the United Kingdom and United States governing the design of ventilation systems for hospital wards and other multibed rooms. In addition, an analytical computational fluid dynamics (CFD) study was performed to evaluate the effectiveness of various ventilation strategies in removing airborne pathogens from ward spaces. RESULTS The CFD simulation showed the bioaerosol concentration in the study room to be substantially lower (2467 cfu/m(3)) when air was supplied and extracted through the ceiling compared with other simulated ventilations strategies, which achieved bioaerosol concentrations of 12487 and 10601 cfu/m(3), respectively. CONCLUSIONS There is a growing body of evidence that the aerial dispersion of some nosocomial pathogens can seed widespread environmental contamination, and that this may be contributing to the spread infection in hospital wards. Acinetobacter spp in particular appear to conform to this model, with numerous outbreaks attributed to aerial dissemination. This suggests that the clinical role of general ward ventilation may have been underestimated and that through improved ward ventilation, it may be possible to reduce environmental contamination and thus reduce nosocomial infection rates.

Bactericidal action of positive and negative ions in air

BackgroundIn recent years there has been renewed interest in the use of air ionisers to control of the spread of airborne infection. One characteristic of air ions which has been widely reported is their apparent biocidal action. However, whilst the body of evidence suggests a biocidal effect in the presence of air ions the physical and biological mechanisms involved remain unclear. In particular, it is not clear which of several possible mechanisms of electrical origin (i.e. the action of the ions, the production of ozone, or the action of the electric field) are responsible for cell death. A study was therefore undertaken to clarify this issue and to determine the physical mechanisms associated with microbial cell death.ResultsIn the study seven bacterial species (Staphylococcus aureus, Mycobacterium parafortuitum, Pseudomonas aeruginosa, Acinetobacter baumanii, Burkholderia cenocepacia, Bacillus subtilis and Serratia marcescens) were exposed to both positive and negative ions in the presence of air. In order to distinguish between effects arising from: (i) the action of the air ions; (ii) the action of the electric field, and (iii) the action of ozone, two interventions were made. The first intervention involved placing a thin mica sheet between the ionisation source and the bacteria, directly over the agar plates. This intervention, while leaving the electric field unaltered, prevented the air ions from reaching the microbial samples. In addition, the mica plate prevented ozone produced from reaching the bacteria. The second intervention involved placing an earthed wire mesh directly above the agar plates. This prevented both the electric field and the air ions from impacting on the bacteria, while allowing any ozone present to reach the agar plate. With the exception of Mycobacterium parafortuitum, the principal cause of cell death amongst the bacteria studied was exposure to ozone, with electroporation playing a secondary role. However in the case of Mycobacterium parafortuitum, electroporation resulting from exposure to the electric field appears to have been the principal cause of cell inactivation.ConclusionThe results of the study suggest that the bactericidal action attributed to negative air ions by previous researchers may have been overestimated.

CFD simulation of airborne pathogen transport due to human activities

Abstract Computational Fluid Dynamics (CFD) is an increasingly popular tool for studying the impact of design interventions on the transport of infectious microorganisms. While much of the focus is on respiratory infections, there is substantial evidence that certain pathogens, such as those which colonise the skin, can be released into, and transported through the air through routine activities. In these situations the bacteria is released over a volume of space, with different intensities and locations varying in time rather than being released at a single point. This paper considers the application of CFD modelling to the evaluation of risk from this type of bioaerosol generation. An experimental validation study provides a direct comparison between CFD simulations and bioaerosol distribution, showing that passive scalar and particle tracking approaches are both appropriate for small particle bioaerosols. The study introduces a zonal source, which aims to represent the time averaged release of bacteria from an activity within a zone around the entire location the release takes place. This approach is shown to perform well when validated numerically though comparison with the time averaged dispersion patterns from a transient source. However, the ability of a point source to represent such dispersion is dependent on airflow regime. The applicability of the model is demonstrated using a simulation of an isolation room representing the release of bacteria from bedmaking.

Mathematical models for assessing the role of airflow on the risk of airborne infection in hospital wards

Understanding the risk of airborne transmission can provide important information for designing safe healthcare environments with an appropriate level of environmental control for mitigating risks. The most common approach for assessing risk is to use the Wells–Riley equation to relate infectious cases to human and environmental parameters. While it is a simple model that can yield valuable information, the model used as in its original presentation has a number of limitations. This paper reviews recent developments addressing some of the limitations including coupling with epidemic models to evaluate the wider impact of control measures on disease progression, linking with zonal ventilation or computational fluid dynamics simulations to deal with imperfect mixing in real environments and recent work on dose–response modelling to simulate the interaction between pathogens and the host. A stochastic version of the Wells–Riley model is presented that allows consideration of the effects of small populations relevant in healthcare settings and it is demonstrated how this can be linked to a simple zonal ventilation model to simulate the influence of proximity to an infector. The results show how neglecting the stochastic effects present in a real situation could underestimate the risk by 15 per cent or more and that the number and rate of new infections between connected spaces is strongly dependent on the airflow. Results also indicate the potential danger of using fully mixed models for future risk assessments, with quanta values derived from such cases less than half the actual source value.

Modelling the Performance of Upper Room Ultraviolet Germicidal Irradiation Devices in Ventilated Rooms: Comparison of Analytical and CFD Methods

Models to evaluate upper room ultraviolet germicidal irradiation (UVGI) devices can be used to improve the understanding of the behaviour of UV devices in ventilated rooms and so enable more confident predictions to be made of their performance. This paper presents two- and three-zone mixing models for investigating the effect of upper room UVGI devices in a typical ventilated room. The results from these analytical models are compared to a CFD simulation of the same room that incorporates the biological inactivation of micro-organisms in the presence of an ultraviolet field. The study demonstrates that analytical mixing models give reasonably good average zone concentrations and are therefore useful in estimating overall performance. However, the CFD simulations are necessary to fully examine the interaction of the room airflow with the inactivation of micro-organisms due to the UV field.

Use of CFD modelling to optimise the design of upper-room UVGI disinfection systems for ventilated rooms

The installation of upper-room ultraviolet germicidal irradiation (UVGI) devices in ventilated rooms has the potential to reduce transmission of infections by an airborne route. However, the performance of such devices is dependant on several factors including the location of the lamp and the ventilation airflow in the room. This study uses a CFD model to evaluate the performance of UVGI devices by considering the cumulative UV-C dose received by the bulk room air in a ventilated room. By evaluating the UV dose rather than the resulting micro-organism inactivation the methodology can be used to optimise UVGI systems at the design stage, particularly when the source location of bioaerosol contaminants is not known. The study investigates the relationships between the lamp location, lamp power, ventilation system and room heating in a small, ventilated room. The results show that with ventilation air supplied at low level and extracted at high level the UVGI system performs better than with the air supplied at high level and extracted close to the floor. In addition the results show the presence of a heater in the room is unlikely to have a detrimental effect on performance and may promote mixing to increase the extent of disinfection.

Use of CFD Analysis in Modifying a TB Ward in Lima, Peru

The high world-wide prevalence of tuberculosis (TB) and the increase in multi-drug resistant strains (MDRTB) have prompted increased interest in engineering control solutions such as ventilation system design and the use of ultraviolet germicidal irradiation (UVGI). This study considers the contribution of the ventilation airflow to the transmission of TB, and uses computational fluid dynamics (CFD) simulations to examine how changes in the design of a ward, in Hospital Nacional Dos de Mayo, Lima, Peru may reduce the transmission of TB from patients to health-care workers, visitors and other patients. The results of this study were used to advise the architects and engineers in the remodelling of the ward.