Process measure of FAST tuberculosis infection control demonstrates delay in likely effective treatment.

SETTING: The tuberculous infection control strategy, FAST (Find cases Actively, Separate safely and Treat effectively), recommends prompt initiation of likely effective anti-tuberculosis treatment informed by Xpert® MTB/RIF results.OBJECTIVE: To describe FAST implementation at Quang Nam Provincial TB and Lung Disease Hospital (QNH), Tam Ky, Viet Nam, using time to initiation of effective TB treatment as a process measure. DESIGN: Hospital logs were used to calculate the time to likely effective treatment in patients with pulmonary TB (PTB) hospitalised during the study period. RESULTS: Between 1 January and 31 December 2016, of 858 patients treated for PTB, 493 (57.5%) received likely effective treatment. The median time to likely effective treatment was 3 days (interquartile range 2.0-6.0), with 213 (43.2%) patients receiving likely effective treatment within 2 days. Of 81 patients receiving likely effective treatment for drug-susceptible TB with a positive Xpert result as their initial in-patient diagnostic test, 64 (79.0%) received likely effective treatment within 2 days compared with 10 (5.7%) who were initially smear-negative then found to be Xpert-positive (P < 0.0001). CONCLUSIONS: A 'time to' process measure of the FAST tuberculous infection control strategy indicates delays in the initiation of likely effective anti-tuberculosis treatment in a resource-limited hospital. Expanding access to Xpert may speed time to likely effective treatment.

Inhaled drug treatment for tuberculosis: Past progress and future prospects.

Since the 1990s the rising incidence of multiple drug resistant TB, particularly in the context of human immunodeficiency virus co-infected patients, has threatened global TB control. At that time funding agencies began to support formal investigation of aerosol therapy which until then had been the subject of case reports of individual investigators. Over the last decade, proponents of aerosol therapy have increased in number within the TB research community as the incidence of multiple and extremely drug resistant TB has increased dramatically around the world. Aerosol therapy offers the potential to deliver drug at target concentrations directly into the lungs, use the alveolar-capillary interface to achieve systemic levels, while reducing the risk of systemic toxicity seen with parentally administered doses. In addition, there are insufficient new drugs in the pipeline to anticipate the appearance of a new regimen in time to assure future control of drug resistance. Consequently, alternative strategies are critical to achieving global TB control, and inhaled therapies should be considered as one such strategy.

Indoor environmental control of tuberculosis and other airborne infections.

Tuberculosis (TB) remains the airborne infection of global importance, although many environmental interventions to control TB apply to influenza and other infections with airborne potential. This review focuses on the global problem and the current state of available environmental interventions. TB transmission is facilitated in overcrowded, poorly ventilated congregate settings, such as hospitals, clinics, prisons, jails, and refugee camps. The best means of TB transmission control is source control- to identify unsuspected infectious cases and to promptly begin effective therapy. However, even with active case finding and rapid diagnostics, not every unsuspected case will be identified, and environmental control measures remain the next intervention of choice. Natural ventilation is the main means of air disinfection and has the advantage of wide availability, low cost, and high efficacy-under optimal conditions. It is usually not applicable all year in colder climates and may not be effective when windows are closed on cold nights in warm climates, for security, and for pest control. In warm climates, windows may be closed when air conditioning is installed for thermal comfort. Although mechanical ventilation, if properly installed and maintained, can provide adequate air disinfection, it is expensive to install, maintain, and operate. The most cost-effective way to achieve high levels of air disinfection is upper room germicidal irradiation. The safe and effective application of this poorly defined intervention is now well understood, and recently published evidence-based application guidelines will make implementation easier.

Eggcrate UV: a whole ceiling upper-room ultraviolet germicidal irradiation system for air disinfection in occupied rooms.

A novel whole ceiling upper-room ultraviolet germicidal irradiation (UVGI) system [eggcrate ultraviolet (UV)] has been developed that incorporates open-cell 'eggcrate'-suspended ceiling panels and bare UV lamps with a ceiling fan. Upper-room UVGI is more effective for air disinfection than mechanical ventilation at much lower installation and operating costs. Conventional upper-room UVGI fixtures employ multiple tightly spaced horizontal louvers to confine UV to the upper-room. These louvered fixtures protect occupants in the lower-room from UV-induced eye and skin irritation, but at a major cost to fixture efficiency. Using a lamp and ballast from a conventional upper-room UVGI fixture in the eggcrate UV system, the germicidal efficacy was markedly improved even though the UV radiation emitted by the lamp was unchanged. This fundamental change in the application of upper-room UVGI air disinfection should permit wider, more effective application of UVGI globally to reduce the spread of airborne infection.

Treating multidrug-resistant tuberculosis in Tomsk, Russia: developing programs that address the linkage between poverty and disease.

Tuberculosis (TB) and multidrug-resistant TB (MDR-TB) are diseases of poverty. Because Mycobacterium tuberculosis exists predominantly in a social space often defined by poverty and its comorbidities--overcrowded or congregate living conditions, substance dependence or abuse, and lack of access to proper health services, to name a few--the biology of this organism and of TB drug resistance is intimately linked to the social world in which patients live. This association is demonstrated in Russia, where political changes in the 1990s resulted in increased socioeconomic inequality and a breakdown in health services. The effect on TB and MDR-TB is reflected both in terms of a rise in TB and MDR-TB incidence and increased morbidity and mortality associated with the disease. We present the case example of Tomsk Oblast to delineate how poverty contributed to a growing MDR-TB epidemic and increasing socioeconomic barriers to successful care, even when available. The MDR-TB pilot project implemented in Tomsk addressed both programmatic and socioeconomic factors associated with unfavorable outcomes. The result has been a strengthening of the overall TB control program in the region and improved case-holding for the most vulnerable patients. The model of MDR-TB care in Tomsk is applicable for other resource-poor settings facing challenges to TB and MDR-TB control.

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.

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.

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.

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.

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.