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Edward A. Nardell

Bio: Edward A. Nardell is an academic researcher from Brigham and Women's Hospital. The author has contributed to research in topics: Tuberculosis & Ultraviolet germicidal irradiation. The author has an hindex of 40, co-authored 142 publications receiving 5259 citations. Previous affiliations of Edward A. Nardell include Cambridge Hospital & Partners In Health.


Papers
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Journal ArticleDOI
TL;DR: Several lines of evidence suggest that alternative mechanisms-including pharmacokinetic variability, induction of efflux pumps that transport the drug out of cells, and suboptimal drug penetration into tuberculosis lesions-are likely crucial to the pathogenesis of drug-resistant tuberculosis.

461 citations

Journal ArticleDOI
TL;DR: It is hypothesized that, by altering lung airway surface properties through an inhaled nontoxic aerosol, this work might substantially diminish the number of exhaled bioaerosol droplets and thereby provide a simple means to potentially mitigate the spread of airborne infectious disease independently of the identity of the airborne pathogen or the nature of any specific therapy.
Abstract: Humans commonly exhale aerosols comprised of small droplets of airway-lining fluid during normal breathing. These “exhaled bioaerosols” may carry airborne pathogens and thereby magnify the spread of certain infectious diseases, such as influenza, tuberculosis, and severe acute respiratory syndrome. We hypothesize that, by altering lung airway surface properties through an inhaled nontoxic aerosol, we might substantially diminish the number of exhaled bioaerosol droplets and thereby provide a simple means to potentially mitigate the spread of airborne infectious disease independently of the identity of the airborne pathogen or the nature of any specific therapy. We find that some normal human subjects expire many more bioaerosol particles than other individuals during quiet breathing and therefore bear the burden of production of exhaled bioaerosols. Administering nebulized isotonic saline to these “high-producer” individuals diminishes the number of exhaled bioaerosol particles expired by 72.10 ± 8.19% for up to 6 h. In vitro and in vivo experiments with saline and surfactants suggest that the mechanism of action of the nebulized saline relates to modification of the physical properties of the airway-lining fluid, notably surface tension.

331 citations

Journal ArticleDOI
TL;DR: It is concluded that exogenous reinfection may have been an important factor leading to highly contagious secondary cases and an acceleration of the usual pattern of tuberculosis transmission in this highly susceptible population of homeless people.
Abstract: We investigated an outbreak of tuberculosis in a large shelter for the homeless to assess the role of exogenous reinfection as opposed to reactivation of endogenous infection as the cause of secondary tuberculosis in this population. Exogenous reinfection is considered relatively unimportant in the United States and other developed countries. Of 49 shelter-related cases, 22 had cultures resistant to both isoniazid and streptomycin and of the same phage type, indicating recent transmission originating with a single index patient. The probable index patient had a 10-year history of isoniazid and streptomycin resistance — an uncommon pattern at the shelter during the three years preceding the outbreak. In 4 of the 22 cases, the patient had previously had documented tuberculosis infection or disease. These reinfected patients had extensive lung cavitation and numerous acid-fast bacilli on sputum smears — features associated with contagiousness. In contrast, patients with tuberculosis for the first ti...

260 citations

Journal ArticleDOI
TL;DR: It is concluded that outdoor air ventilation that is inadequate for comfort may contribute to airborne infection but that the protection afforded to building occupants by ventilation above comfort levels may be inherently limited, especially when the level of exposure to infection is high.
Abstract: Of 67 office workers 27 (40%) had documented tuberculin skin test conversions after an estimated 4-wk exposure to a coworker with cavitary tuberculosis. Worker complaints for more than 2 yr before the tuberculosis exposure prompted investigations of air quality in the building before and after the tuberculosis exposure. Carbon dioxide concentrations in many parts of the building were found to be above recommended levels, indicating suboptimal ventilation with outdoor air. We applied a mathematical model of airborne transmission to the data to assess the role of building ventilation and other transmission factors. We estimated that ventilation with outside air averaged about 15 feet 3/min (cfm) per occupant, the low end of acceptable ventilation, corresponding to CO2 levels of about 1,000 ppm. The model predicted that at 25 cfm per person 18 workers would have been infected (a 33% reduction) and at 35 cfm, a level considered optimal for comfort, that 13 workers would have been infected (an additional 19% reduction). Further increases in outdoor air ventilation would be impractical and would have resulted in progressively smaller increments in protection. According to the model, the index case added approximately 13 infectious doses (quanta) per hour (qph) to the office air during the exposure period, 10 times the average infectiousness reported in a large series of tuberculosis cases. Further modeling predicted that as infectiousness rises, ventilation would offer progressively less protection. We conclude that outdoor air ventilation that is inadequate for comfort may contribute to airborne infection but that the protection afforded to building occupants by ventilation above comfort levels may be inherently limited, especially when the level of exposure to infection is high.

238 citations

Journal ArticleDOI
TL;DR: Of the many infectious organisms that are susceptible to UV, most attention has been focused on measles and tuberculosis because of their importance as airborne infections and because each has characteristics favorable for epidemiologic study.
Abstract: In the 1940s and 1950s, both the potential and the problems of interrupting transmission of airborne infection with ultraviolet (UV) light were demonstrated William F Wells first introduced the concept of droplet nuclei as the vehicles of airborne transmission and later showed that these nearly naked, suspended organisms were highly susceptible to inactivation by UV light of 254 nm wavelength (1, 2) Of the many infectious organisms that are susceptible to UV, most attention has been focused on measles and tuberculosis (TB) because of their importance as airborne infections and because each has characteristics favorable for epidemiologic study In his classic experiment of 1942, Wells used UV light in schools to prevent the epidemic spread of measles (3) However, the inability of others to repeat Wells' success led to disillusionment (4, 5) Antiultraviolet sentiment was further fueled by concern about ozone production (negligible with current 254 nm wavelength bulbs) and by concerns about skin and eye

186 citations


Cited by
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Journal ArticleDOI
17 Nov 2005-Nature
TL;DR: It is shown that contact tracing data from eight directly transmitted diseases shows that the distribution of individual infectiousness around R0 is often highly skewed, and implications for outbreak control are explored, showing that individual-specific control measures outperform population-wide measures.
Abstract: Population-level analyses often use average quantities to describe heterogeneous systems, particularly when variation does not arise from identifiable groups. A prominent example, central to our current understanding of epidemic spread, is the basic reproductive number, R(0), which is defined as the mean number of infections caused by an infected individual in a susceptible population. Population estimates of R(0) can obscure considerable individual variation in infectiousness, as highlighted during the global emergence of severe acute respiratory syndrome (SARS) by numerous 'superspreading events' in which certain individuals infected unusually large numbers of secondary cases. For diseases transmitted by non-sexual direct contacts, such as SARS or smallpox, individual variation is difficult to measure empirically, and thus its importance for outbreak dynamics has been unclear. Here we present an integrated theoretical and statistical analysis of the influence of individual variation in infectiousness on disease emergence. Using contact tracing data from eight directly transmitted diseases, we show that the distribution of individual infectiousness around R(0) is often highly skewed. Model predictions accounting for this variation differ sharply from average-based approaches, with disease extinction more likely and outbreaks rarer but more explosive. Using these models, we explore implications for outbreak control, showing that individual-specific control measures outperform population-wide measures. Moreover, the dramatic improvements achieved through targeted control policies emphasize the need to identify predictive correlates of higher infectiousness. Our findings indicate that superspreading is a normal feature of disease spread, and to frame ongoing discussion we propose a rigorous definition for superspreading events and a method to predict their frequency.

2,274 citations

Journal ArticleDOI
TL;DR: The MTB/RIF test provided sensitive detection of tuberculosis and rifampin resistance directly from untreated sputum in less than 2 hours with minimal hands-on time.
Abstract: Background Global control of tuberculosis is hampered by slow, insensitive diagnostic methods, particularly for the detection of drug-resistant forms and in patients with human immunodeficiency virus infection. Early detection is essential to reduce the death rate and interrupt transmission, but the complexity and infrastructure needs of sensitive methods limit their accessibility and effect. Methods We assessed the performance of Xpert MTB/RIF, an automated molecular test for Mycobacterium tuberculosis (MTB) and resistance to rifampin (RIF), with fully integrated sample processing in 1730 patients with suspected drug-sensitive or multidrug-resistant pulmonary tuberculosis. Eligible patients in Peru, Azerbaijan, South Africa, and India provided three sputum specimens each. Two specimens were processed with N-acetyl-l-cysteine and sodium hydroxide before microscopy, solid and liquid culture, and the MTB/RIF test, and one specimen was used for direct testing with microscopy and the MTB/RIF test. Results Among culture-positive patients, a single, direct MTB/RIF test identified 551 of 561 patients with smear-positive tuberculosis (98.2%) and 124 of 171 with smear-negative tuberculosis (72.5%). The test was specific in 604 of 609 patients without tuberculosis (99.2%). Among patients with smear-negative, culture-positive tuberculosis, the addition of a second MTB/RIF test increased sensitivity by 12.6 percentage points and a third by 5.1 percentage points, to a total of 90.2%. As compared with phenotypic drug-susceptibility testing, MTB/RIF testing correctly identified 200 of 205 patients (97.6%) with rifampin-resistant bacteria and 504 of 514 (98.1%) with rifampin-sensitive bacteria. Sequencing resolved all but two cases in favor of the MTB/RIF assay. Conclusions The MTB/RIF test provided sensitive detection of tuberculosis and rifampin resistance directly from untreated sputum in less than 2 hours with minimal hands-on time. (Funded by the Foundation for Innovative New Diagnostics.)

2,086 citations

Journal ArticleDOI
TL;DR: Radiographic evidence of Prior Tuberculosis: Inactive Tuber tuberculosis and Culture-negative Pulmonary Tuber TB in Adults is presented.
Abstract: 8.4. Culture-negative Pulmonary Tuberculosis CONTENTS in Adults . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 650 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 604 8.5. Radiographic Evidence of Prior Tuberculosis: Inactive Tuberculosis . . . . . . . . . . . . . . . . . . . . . 650

1,887 citations

Journal ArticleDOI
TL;DR: MDR tuberculosis is more prevalent than previously realised in a rural area in KwaZulu Natal, South Africa and has been transmitted to HIV co-infected patients and is associated with high mortality.

1,601 citations

01 Jan 2011
TL;DR: This report reviews previous guidelines and strategies for preventing environment-associated infections in health-care facilities and offers recommendations, including evidence-based recommendations supported by studies and experienced opinions based upon infection-control and engineering practices.
Abstract: The health-care facility environment is rarely implicated in disease transmission, except among patients who are immunocompromised. Nonetheless, inadvertent exposures to environmental pathogens (e.g., Aspergillus spp. and Legionella spp.) or airborne pathogens (e.g., Mycobacterium tuberculosis and varicella-zoster virus) can result in adverse patient outcomes and cause illness among health-care workers. Environmental infection-control strategies and engineering controls can effectively prevent these infections. The incidence of health-care--associated infections and pseudo-outbreaks can be minimized by 1) appropriate use of cleaners and disinfectants; 2) appropriate maintenance of medical equipment (e.g., automated endoscope reprocessors or hydrotherapy equipment); 3) adherence to water-quality standards for hemodialysis, and to ventilation standards for specialized care environments (e.g., airborne infection isolation rooms, protective environments, or operating rooms); and 4) prompt management of water intrusion into the facility. Routine environmental sampling is not usually advised, except for water quality determinations in hemodialysis settings and other situations where sampling is directed by epidemiologic principles, and results can be applied directly to infection-control decisions. This report reviews previous guidelines and strategies for preventing environment-associated infections in health-care facilities and offers recommendations. These include 1) evidence-based recommendations supported by studies; 2) requirements of federal agencies (e.g., Food and Drug Administration, U.S. Environmental Protection Agency, U.S. Department of Labor, Occupational Safety and Health Administration, and U.S. Department of Justice); 3) guidelines and standards from building and equipment professional organizations (e.g., American Institute of Architects, Association for the Advancement of Medical Instrumentation, and American Society of Heating, Refrigeration, and Air-Conditioning Engineers); 4) recommendations derived from scientific theory or rationale; and 5) experienced opinions based upon infection-control and engineering practices. The report also suggests a series of performance measurements as a means to evaluate infection-control efforts.

1,478 citations