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Today, March 24, marks World TB Day, which commemorates the date in 1882 when Robert Koch discovered Mycobacterium tuberculosis, the cause of tuberculosis (TB). World TB Day provides an opportunity to raise awareness of the disease and for TB-prevention organizations to support worldwide TB-control efforts. The U.S. theme for this years observance is Partnerships for TB Elimination.
Fundamentals of TB Control and Prevention
One of the most critical risks for transmission of M. tuberculosis in healthcare settings is from patients with unrecognized TB disease who are not promptly handled with appropriate airborne precautions or who are moved from an isolation room too soon. In the United States, the problem of multidrug-resistant TB (MDRTB), which was amplified by healthcare-associated transmission, has been substantially reduced by the use of standardized anti-tuberculosis treatment regimens in the initial phase of therapy, rapid drug-susceptibility testing, airborne infection isolation when necessary,Â directly observed therapy (DOT), and improved infection control practices. DOT is an adherence-enhancing strategy in which a healthcare professional watches a patient swallow each dose of medication and records the dates that the administration was observed. DOT is the standard of care for all patients with TB disease and should be used for all doses during the course of therapy for TB disease and for LTBI, whenever possible.
The Centers for Disease Control and Prevention (CDC) says that all healthcare facilities need a TB prevention and control program designed to ensure prompt detection, airborne precautions, and treatment of persons who have suspected or confirmed TB disease (or prompt referral of persons who have suspected TB disease for settings in which persons with TB disease are not expected to be encountered). Such a program is based on a three-level hierarchy of controls, including administrative, environmental, and respiratory protection.
Droplet nuclei are responsible for transmitting tuberculosis infection, but they can be an elusive substance to capture. Edward A. Nardell, MD, in the white paper titled, Catching Droplet Nuclei: Toward a Better Understanding of Tuberculosis Transmission (American Journal of Respiratory and Critical Care Medicine, March 1, 2004), writes,Â Â Tuberculosis is among humankind's most successful pathogens, almost every case the result of airborne transmission, and yet we know relatively little of its aerobiology. Apart from established transmission factors like cough frequency, lung cavitation, and sputum smear status, we know little about why some patients are disseminators while others infect few if any contacts. How important are the physical properties of the lung lining fluid that must be aerosolized to form droplet nuclei? Could these be manipulated to reduce contagion? Do tuberculosis strains vary in their ability to resist damage caused by aerosolization, by dehydration during airborne transport, and by rehydration upon inhalation by a new host? How long do tubercle bacilli survive in air under various conditions? Does ambient high humidity in tropical regions favor transmission? In addition to germicidal irradiation, are there other ways to make high-risk environments less favorable for transmission? The answers to these and other basic transmission questions will likely lead to new ways to reduce transmission, but they will not likely come from epidemiological investigations alone.
There are a number of ways to control the spread of TB. Administrative controls include conducting a facility-wide TB risk assessment;Â developing and instituting a written TB control plan to ensure prompt detection and isolation of infected patients, airborne precautions, and treatment of persons who have suspected or confirmed TB disease; ensuring proper cleaning and sterilization or disinfection of potentially contaminated equipment (usually endoscopes); educating healthcare workers about TB, with specific focus on prevention, transmission, and symptoms;Â screening and evaluating healthcare workers who are at risk for TB disease or who might be exposed to M. tuberculosis; using appropriate signage advising respiratory hygiene and cough etiquette; andÂ coordinating efforts with the local or state health department.
A critical way to control the transmission of TB is to use proper respiratory protective equipment in situations that pose a high risk for exposure. Use of respiratory protection can further reduce risk for exposure of healthcare workers to infectious droplet nuclei that have been expelled into the air from a patient with infectious TB disease. The following measures can be taken to reduce the risk for exposure: implementing a respiratory protection program, educating healthcare workers about respiratory protection, and training patients on respiratory hygiene and cough etiquette procedures.
Environmental controls also can be used to prevent the spread and reduce the concentration of infectious droplet nuclei in ambient air. Primary environmental controls consist of controlling the source of infection by using local exhaust ventilation (such as anterooms, portable containment units, tents, hoods or booths) and diluting and removing contaminated air by using general ventilation. Secondary environmental controls consist of controlling the airflow to prevent contamination of air in areas adjacent to the source and cleaning the air by using high efficiency particulate air (HEPA) filtration or UVGI.Â
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The Scope of the TB Problem
Despite global eradication efforts by the World Health Organization (WHO) and other agencies, tuberculosis has infected at least 2 billion people, or one-third of the worlds population, according to the CDC. In 2005 alone, approximately 8.8 million people became ill from TB, and 1.6 million died. Whats more, TB is making a comeback; after three decades of decline, the number of TB cases reported in the United States increased 20 percent from 1985 to 1992, according to the CDC.(1) Although the 2007 TB rate (4.4 cases per 100,000 population) was the lowest recorded in the United States since national reporting began in 1953, the average annual decline has slowed since 2000. In addition, MDR-TB remains a threat, and extensively drug-resistant TB has become an emerging threat.
Last week, the WHO released its Global Tuberculosis Control 2008 report, which finds that the pace of the progress to control the TB epidemic slowed slightly in 2006, the most recent year for which data were available. The new information documents a slowdown in progress on diagnosing people with TB. Between 2001 and 2005, the average rate at which new TB cases were detected was increasing by 6 percent per year; but between 2005 and 2006 that rate of increase was cut in half, to 3 percent.
The reason for this slowing of progress is that some national programs that were making rapid strides during the previous five years have been unable to continue at the same pace in 2006. Moreover, in most African countries there has been no increase in the detection of TB cases through national programs. Other studies have also shown that many patients are treated by private care providers, and by non-governmental, faith-based and community organizations, thus escaping detection by the public programs.
We've entered a new era," says Dr. Margaret Chan, WHO director-general. To make progress, firstly public programs must be further strengthened. Secondly, we need to fully tap the potential of other service providers. Enlisting these other providers, working in partnership with national programs, will markedly increase diagnosis and treatment for people in need.
The lethal combination of TB and human immunodeficiency virus (HIV), which is fueling the TB epidemic in many parts of the world, especially Africa, is of utmost concern to public health experts. Although TB/HIV remains a massive challenge, some countries are making strides against the co-epidemic. Almost 700 000 TB patients were tested for HIV in 2006, up from 22 000 in 2002 -- a sign of progress but still far from the 2006 target of 1.6 million set by the Global Plan to Stop TB 2006-2015.
The report tells us that we are far from providing universal access to high-quality prevention, diagnostic, treatment and care services for HIV and TB," says Dr. Peter Piot, executive director of UNAIDS, the Joint United Nations Program on HIV/AIDS. Clear progress has been made but we must all do more to make a joint approach to reducing TB deaths among people with HIV a reality.
TB Trends in 2007
The March 18, 2008 issue of the CDCs Morbidity and Mortality Weekly Report provides a snapshot of the most recent trends in tuberculosis in the United States.(1) The MMWR says that in 2007, a total of 13,293 tuberculosis (TB) cases were reported in the United States; the TB rate declined 4.2 percent from 2006 to 4.4 cases per 100,000 population. This data was gleaned from the National TB Surveillance System and describes trends since 1993. The TB incidence rate in 2007 was the lowest recorded since national reporting began in 1953. Despite this overall improvement, progress has slowed in recent years; the average annual percentage decline in the TB rate slowed from 7.3 percent per year from 1993 to 2000 to 3.8 percent from 2000 to 2007.
Foreign-born individuals and racial/ethnic minorities continued to bear a disproportionate burden of TB disease in the United States. In 2007, the TB rate in foreign-born persons in the United States was 9.7 times higher than in U.S.-born persons. The slowing decline in TB incidence and persistent disparities between U.S.-born and foreign-born persons and between whites and minorities threaten progress toward TB elimination in the United States. The strategic plan for the elimination of TB issued in 1989 by CDC and the Advisory Committee for the Elimination of Tuberculosis set a goal of TB elimination (i.e., less than one case per 1 million population) by 2010 and an interim target case rate of 3.5 per 100,000 population by 2000.(3)
Health departments in the 50 states and the District of Columbia (DC) electronically report to CDC verified TB cases that meet the CDC/Council of State and Territorial Epidemiologists case definition. Reports include the patients race, ethnicity, treatment information, and, whenever available, drug-susceptibility test results. CDC calculates national and state TB rates overall, by country of origin, and by racial/ethnic group by using current U.S. census population estimates. In 2007, TB rates in reporting areas ranged from 0.4 cases in Wyoming) to 10.2 cases in the District of Columbia per 100,000 population (median: 3.5 cases). In 2007, more than half of U.S. states had TB rates less than or equal to the 2000 interim target case rate of 3.5 per 100,000 population; however, 12 of those 26 had higher rates of TB in 2007 than in 2006. Five states (California, Florida, Illinois, New York, and Texas) reported more than 500 cases each for 2007; combined, these five states accounted for more than half of all TB cases.
Multidrug-resistant TB Rates
The CDC reports that a total of 116 cases of MDR TB, defined as a case of TB in a person with a Mycobacterium tuberculosis isolate resistant to at least isoniazid and rifampin -- were reported in 2006, the most recent year for which complete drug-susceptibility data are available. The proportion of MDR TB cases was 1.1 percent in 2006 (116 of 10,306), compared with 1.2 percent in 2005 (124 of 10,633). The proportion
of MDR TB cases among persons without a previous history of TB has remained stable at approximately 1.0 percent since 1997, but has been approximately four to five times higher for persons with a previous history of TB. In 2006, MDR TB continued to disproportionately impact foreign-born persons, who accounted for 84.5 percent of MDR
TB cases. Foreign-born persons had higher percentages of MDR TB, both among persons with (7 percent) and without (1.4 percent) a previous history of TB. Since drug-susceptibility reporting began in 1993, cases of extensively drug-resistant TB (XDR TB) have been reported every year in the United States except 2003. Two XDR TB cases were reported in 2005 and four in 2006. As of Feb. 13, 2008, two XDR TB cases had been reported for 2007, according to the CDC.(1)
The Clinical Manifestation of TB
M. tuberculosis is carried in airborne particles called droplet nuclei that can be generated when persons who have pulmonary or laryngeal TB disease cough or sneeze. The particles are approximately 1 to 5 Âµm; normal air currents can keep them airborne for prolonged periods and spread them throughout a room or building. M. tuberculosis is usually transmitted only through air, not by surface contact. After the droplet nuclei are in the alveoli, local infection might be established, followed by dissemination to draining lymphatics and hematogenous spread throughout the body.
Infection occurs when a susceptible person inhales droplet nuclei containing M. tuberculosis, and the droplet nuclei traverse the mouth or nasal passages, upper respiratory tract, and bronchi to reach the alveoli. Persons with TB pleural effusions might also have concurrent unsuspected pulmonary or laryngeal TB disease. Usually within two weeks to 12 weeks after initial infection with M. tuberculosis, the immune response limits additional multiplication of the tubercle bacilli, and immunologic test results for M. tuberculosis infection become positive. However, certain bacilli remain in the body and are viable for multiple years. This condition is referred to as latent tuberculosis infection (LTBI). Persons with LTBI are asymptomatic and are not infectious. Typically, approximately 5 percent to 10 percent of persons who become infected with M. tuberculosis and who are not treated for LTBI will develop TB disease during their lifetimes (1). The risk for progression of LTBI to TB disease is highest during the first several years after infection.(2)
Characteristics of people exposed to M. tuberculosis that might affect the risk for infection are not as well defined. The probability that a person who is exposed to M. tuberculosis will become infected depends primarily on the concentration of infectious droplet nuclei in the air and the duration of exposure to a person with infectious TB disease. The closer the proximity and the longer the duration of exposure, the higher the risk is for being infected. Close contacts are persons who share the same air space in a household or other enclosed environment for a prolonged period (days or weeks, not minutes or hours) with a person with pulmonary TB disease. A suspect TB patient is a person in whom a diagnosis of TB disease is being considered, whether or not antituberculosis treatment has been started. Persons generally should not remain a suspect TB patient for more than three months.(2)
In addition to close contacts, the following persons are also at higher risk for exposure to and infection with M. tuberculosis:
-- Foreign-born persons who have arrived to the United States within five years after moving from geographic areas with a high incidence of TB disease (e.g., Africa, Asia, Eastern Europe, Latin America, and Russia) or who frequently travel to countries with a high prevalence of TB disease.
-- Residents and employees of congregate settings that are high risk, such as correctional facilities, long-term-care facilities and homeless shelters
-- Healthcare professionals who care for high-risk patients
-- Healthcare professionals with unprotected exposure to a patient with TB disease before the identification and correct airborne precautions of the patient.
The following characteristics exist in a patient with TB disease that increases the risk for infectiousness: presence of cough;Â cavitation on chest radiograph;Â positive acid-fast bacilli (AFB) sputum smear result;Â respiratory tract disease with involvement of the larynx (substantially infectious);Â respiratory tract disease with involvement of the lung or pleura (exclusively pleural involvement is less infectious);Â failure to cover the mouth and nose when coughing;Â incorrect, lack of, or short duration of antituberculosis treatment; andÂ undergoing cough-inducing or aerosol-generating procedures such as bronchoscopy, sputum induction, and administration of aerosolized medications
The probability of the risk for transmission of M. tuberculosis is increased as a result of various environmental factors such as: exposure to TB in small, enclosed spaces; inadequate local or general ventilation that results in insufficient dilution or removal of infectious droplet nuclei; recirculation of air containing infectious droplet nuclei; inadequate cleaning and disinfection of medical equipment; and improper procedures for handling specimens.
1. Centers for Disease Control and Prevention. Morbidity and Mortality Weekly Report.
Vol. 57, No. 11. March 21, 2008.Â
2. Centers for Disease Control and Prevention. Guidelines for Preventing the Transmission of Mycobacterium tuberculosis in Health-Care Settings, 2005.
3. Centers for Disease Control and Prevention. A strategic plan for the elimination of tuberculosis in the United States. MMWR 1989;38(No. S-3).
Additional information about World TB Day and CDC TB-elimination activities is available at http://www.cdc.gov/tb/worldtbday.