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Biomedical subjects

E A Nardell

Publications and source records attributed to E A Nardell.

At least 19 recordsLinked to original sources
PubMed2006

Representative drug susceptibility patterns for guiding design of retreatment regimens for MDR-TB.

BACKGROUND: There is no gold standard on how national tuberculosis programs should design retreatment regimens. Often drug susceptibility testing (DST) is not available for all patients, and representative DST patterns in patient populations are used to guide therapy. OBJECTIVES: To examine DST patterns in different patient populations based on previous treatment and to estimate the number of effective anti-tuberculosis agents in several retreatment regimens. METHODS: We reviewed DST results from patients treated with individualized regimens in Peru between January 1998 and July 2004. We stratified patients into four groups based on previous treatment exposure from Group 1 who had failed only one regimen to Group 4 who had failed three regimens. We compared resistance frequencies across the four groups. In Groups 1 and 3, the number of likely effective agents under six possible retreatment regimen scenarios was estimated. RESULTS: Resistance to second-line drugs was significantly higher in groups with more previous courses of treatment. A few retreatment regimens could be identified that would allow at least 80% of patients to receive at least four likely effective drugs. CONCLUSION: Because it is associated with resistance frequencies, previous treatment exposure can serve to guide the design of non-individualized MDR-TB regimens.

Adult↗
PubMed2005

Drug resistance profiles of Mycobacterium tuberculosis isolates: five years' experience and insight into treatment strategies for MDR-TB in Lima, Peru.

SETTING: Lima, Peru. OBJECTIVE: To describe drug resistance profiles of TB isolates from patients at risk for multidrug-resistant tuberculosis (MDR-TB), and to consider the implications of these findings for treatment. DESIGN: Descriptive study of drug susceptibility testing (DST) results for TB isolates from 1680 patients referred for suspicion of MDR-TB between 1996 and 2001. RESULTS: Of 1680 isolates tested, 1144 (68%) were resistant to at least one anti-tuberculosis drug and 926 (55%) were MDR-TB strains. Of 926 MDR isolates, 50 (5%) were resistant to INH and RMP alone, while 367 (40%) were resistant to at least five first-line drugs. We identified 146 unique drug resistance profiles, the most common of which accounted for 11% of drug-resistant isolates. The annual prevalence of isolates with resistance to at least five first-line drugs rose significantly during the study period, from 29% to 37% (P = 0.00086). CONCLUSIONS: This is a group of patients with TB disease among whom the prevalence of a broad spectrum of often highly drug-resistant strains appears to be increasing over time. A single standardized retreatment regimen may be inadequate to cure most patients. Capacity for drug sensitivity testing is essential for development of multiple standardized retreatment or individualized treatment regimens and epidemiological surveillance for planning.

Drug Resistance, Bacterial↗
PubMed2001

Estimation of tuberculosis risk and incidence under upper room ultraviolet germicidal irradiation in a waiting room in a hypothetical scenario.

Environmental control measures (ventilation, high-efficiency particulate air filtration, and upper room ultraviolet germicidal irradiation [UVGI]) are recommended to effectively control tuberculosis (TB) transmission from unsuspected TB patients in high-risk settings, but the effectiveness of their use is not often clear. This study presents a simulation model for a hypothetical hospital waiting room, in which the number of susceptible immunocompetent people in the waiting room follows a Poisson distribution (M = 5) in either low (annual number of TB patients = 5) or high TB risk settings (annual number of TB patients = 50), and used the model to evaluate the reduction of TB transmission risk by upper room UVGI. An exponential dose-response model was used for TB transmission and a two-zone model was used for evaluating the effect of upper room UVGI. Upper room UVGI reduced TB risk by 1.6-fold at 3 microW/cm2 UV irradiance in the upper room in the low TB risk setting and by 4.1-fold at 15 microW/cm2 UV irradiance in the upper room in the high TB risk setting. Use of upper room UVGI also reduced the mean annual new infection rate from 2.2 to 1.3 infections per year at 3 microW/cm2 and to 0.6 infections per year at 15 microW/cm2 in our hypothetical high-risk settings. The effect of upper room UVGI was sensitive to both vertical air velocity (air mixing) and UV irradiance level. Results from partitioning variability indicate that most variability of TB transmission risk came from waiting time in our hypothetical hospital.

Computer Simulation↗
PubMed1998

The relative efficacy of respirators and room ventilation in preventing occupational tuberculosis.

OBJECTIVES: To evaluate the relative efficacy of personal respiratory protection as the concentrations of infectious aerosols increase or as room ventilation rates decrease. METHODS: We modified the Wells-Riley mathematical model of airborne transmission of disease by adding a variable for respirator leakage. We modeled three categories of infectiousness using various room ventilation rates and classes of respirators over a 10-hour exposure period. RESULTS: The risk of infection decreases exponentially with increasing room ventilation or with increasing personal respiratory protection. The relative efficacy of personal respiratory protection decreases as room ventilation rates increase or as the concentrations of infectious aerosols decrease. CONCLUSIONS: These modeling data suggest that the risk of occupational tuberculosis probably can be lowered considerably by using relatively simple respirators combined with modest room ventilation rates for the infectious aerosols likely to be present in isolation rooms of newly diagnosed patients. However, more sophisticated respirators may be needed to achieve a comparable risk reduction for exposures to more highly concentrated aerosols, such as may be generated during cough-inducing procedures or autopsies involving infectious patients. There is probably minimal benefit to the use of respirators in well-ventilated isolation rooms with patients receiving appropriate therapy.

Air Microbiology↗
PubMed1993

Environmental control of tuberculosis.

The premise of this article is that it is possible to reduce but not eliminate the risk of TB infection in many institutional settings through environmental interventions--as supplements to conventional public health TB control efforts. Of the environmental means available to reduce the concentration of infectious droplet nuclei, ventilation, isolation strategies, and personal respirators have received the most attention, but each has inherent limitations. Ventilation and other air-moving strategies (i.e., fan-filter and fan-UV room units) are limited by the large volume of air that must be moved to dilute and remove already dilute droplet nuclei. Isolation assumes that potential transmitters are suspected, whereas negative pressure in isolation rooms is difficult to achieve and maintain in many hospitals. The use of well-designed small enclosures for sputum induction and other high-risk procedures, however, should provide highly effective source control. Personal respirators have a limited protective role because they cannot be worn by all workers at all times, and cannot reasonably be issued to other patients and visitors. Germicidal UV irradiation of upper room air is widely misunderstood, but offers practical air disinfection that can be safely and efficiently deployed in a variety of high-risk environments. Although there are theoretical and experimental bases for these recommendations, there are no clinical field trials preventing TB using any of the available environmental interventions, primarily because of the highly variable nature of TB transmission.

Air Microbiology↗
PubMed1991

Airborne infection. Theoretical limits of protection achievable by building ventilation.

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.

Adult↗
PubMed1991

Treating hard-to-treat tuberculosis patients in Massachusetts.

For most patients with tuberculosis (TB), treatment has never been shorter or cure more certain than with current drug regimens. However, in Massachusetts and elsewhere in the United States there is a growing minority of patients who are not easily cured with the best available outpatient regimens. Close treatment supervision through culturally appropriate outreach workers has been successful for some foreign-born TB patients in whom therapy might otherwise fail. Full supervision of outpatient therapy, sometimes with incentives, has also been used successfully to treat selected homeless patients. However, a growing number of hard-to-treat homeless patients are addicted to illicit drugs, human immunodeficiency virus (HIV) infected, or have major behavioral problems. These patients often do not cooperate with fully supervised therapy and acquire drug resistance as a result of erratic drug taking. They can then transmit these dangerous organisms to others, especially to other HIV-infected persons within shelters, jails, prisons, detoxification centers, clinics, and hospitals, infecting institutional workers at the same time. In Massachusetts these hard-to-treat TB patients are increasingly being legally committed to involuntary, long-term, inpatient therapy. Although long-term inpatient TB treatment is expensive, it is likely to be cost effective when it successfully breaks the chain of transmission within institutions, and achieves cures not otherwise possible. A new model of lower-cost inpatient care that incorporates psychosocial rehabilitation techniques to modify the behavior of the hardest-to-treat patients is briefly described. Ultimately, however, the reversal of the current upsurge in hard-to-treat TB cases in Massachusetts and elsewhere depends not on inpatient care but on substantial changes in the socioeconomic order that perpetuates homelessness, substance abuse, crime, and the transmission of both TB and HIV infections.

Acquired Immunodeficiency Syndrome↗