The resurgence of TB and its implications for radiology.
Tuberculosis poses tremendous risk to certain populations, including HIV-positive or otherwise immunocompromised patients, the homeless and individuals in correctional facilities or nursing homes. Also, tuberculosis is the sixth most common occupationally acquired infection among laboratory workers.
This article traces the etiology of tuberculosis and outlines diagnostic techniques and treatment modalities. It also discusses the role of radiologic technologists in screening patients with suspected tuberculosis.
This article is a Directed Reading. See the quiz at conclusion.
Evidence of tuberculosis can be traced back as far as 10000 B.C. Aristotle (384-322 B.C.) generally is acknowledged as the first person to recognize the contagiousness of the disease, known for thousands of years as "consumption." He observed, "In approaching the consumptive, one breathes pernicious air. One takes the disease because there is in this air something disease-producing."[2-4]
In fact, using a combination of radiography and computed tomography, tubercular lesions have been discovered in the lungs and in extrapulmonary areas of both soft tissue and skeletal remains of neolithic corpses and in Egyptian and pre-Columbian mummies. Recent findings confirm the presence of acid-fast bacilli in human remains from skeletons in Heidelberg, Germany, dating as far back as 5000 B.C. and from 5000-year-old Egyptian mummies. Extensive research is under way to understand the natural history of tuberculosis so the disease can be better understood and treated.
Enrique Gerszten, M.D., professor of pathology at the Medical College of Virginia and specialist in paleopathology, the study of the evolution of human disease, has documented the etiology of tuberculosis in the New World. Working with mummified soft tissue remains from preColumbian corpses, Dr. Gerszten has chronicled the evolution and spread of tuberculosis, coccidioidomycosis (valley fever) and other diseases of the spines throughout the New World. Unlike small pox or malaria, tuberculosis is clearly indigenous to the New World and followed parallel development to its Old World counterpart (Enrique Gerszten, personal communication) .
In addition to the fossil record, evidence of the antiquity of tuberculosis also is supported by the art and literature of ancient mankind. Studies of pre-Columbian and Egyptian skeletons reveal collapse and anterior fusion of adjacent mid-thoracic vertebra, a condition known as Pott's disease or skeletal tuberculosis. In skeletal tuberculosis, the disk space between the vertebra usually is destroyed, producing anterior wedging of the two adjacent vertebra with loss of interstitial disk space. The resulting pathology generally produces a characteristic protuberance in the thoracic region of the spine, a condition commonly referred to as a "hunchback." (See Fig. 1.)
This pathology is depicted in Egyptian tomb inscriptions of hunchback figures from the early Dynastic period, dating as far back as 3500 B.C. In the Americas, the Kokopelli, or hunchbacked flute player, is a common representation in early prehistoric American art. Although the Kokopelli's hunchback (see Fig. 2) could be interpreted as a graphic representation of skeletal tuberculosis, some experts argue that the rounded nature of the spine may not be indicative of tuberculosis, which tends to have a more angular distortion of the spine like that seen in the early Egyptian inscriptions. Ancient Egyptian papyri refer to cases of cervical lymphadenopathy, suggesting a diagnosis of tuberculosis. Chinese writings dating from 2700 B.C. describe lung fever and cough in conjunction with the expectoration of blood and sputum and a general wasting syndrome that are strongly suggestive of tuberculosis. Greek literature also contained numerous references to tuberculosis, confirming the hypothesis that tuberculosis is as ancient as mankind itself.[9-12]
Mycobacteria are believed to be among the oldest bacteria on the earth, and they are endemic in the environment as free-living organisms found in the soil, animal dung, salt and fresh water, mud flats and attached to algae and grasses. They are potentially pathogenic to many animals, including cattle and pigs, as well as reptiles and fish. Cattle are considered to be the original source of human infection. Tuberculosis can be spread by the ingestion of milk contaminated with Mycobacterium bovis. The discovery of the pasteurization process helped eliminate the spread of M. bovis through contaminated milk products, and today the incidence of bovine tuberculosis in humans is rare
It has been postulated that Mycobacterium tuberculosis is a mutant of the bovine form of the bacilli, and it is interesting to note that evidence suggestive of tuberculosis in humans appears in the fossil record during the Neolithic period, or just about the time that cattle first became domesticated. The importance of transmission of tubercle bacilli (M. bovis) from animals to humans was recognized in the early 1900s, and compulsory pasteurization ordinances were adopted in Chicago and New York soon afterward. When pasteurization was adopted there was a concomitant decrease in the incidence of tuberculosis in children. Outbreaks of M. bovis infection in children and adults still is a health problem in developing countries where pasteurization of milk is not practiced.
Although ancient in the historical record, tuberculosis did not become a major cause of mortality until crowded urban living conditions prompted by the industrial revolution created ideal circumstances for transmission of the disease. In the 17th and 18th centuries, tuberculosis caused one-fourth of adult deaths in Europe. The disease was the leading cause of death in the United States from the 1800s until the early 1900s, with mortality rates of 1 per 100.[15,16]
Clinical features of tuberculosis -- cough, prolonged fevers, bloody sputum and wasting -- were well recognized by then. However, there was disagreement among medical professionals as to the disease's cause and etiology. In southern Europe, researchers believed tuberculosis was contagious, whereas in northern Europe, the high incidence of familial cases of tuberculosis led the scientific community to believe that tuberculosis was an inherited disease.[2,6,17]
The mystery surrounding the transmission of tuberculosis ended in 1865, when Francoise Villemin demonstrated that the disease could be transmitted by injecting infected tissue into a guinea pig. In 1882, German bacteriologist and Nobel laureate Robert Koch identified the tubercle bacillus and documented its pathogenicity. In the latter part of the 19th century, it was believed that rest in open air, often in specialized hospitals and sanatoria, was the proper treatment. With the discovery of the x-ray in 1895, it became clear that the development of the pulmonary cavity was fundamental in the development of the disease, and most therapeutic measures were aimed at closure of the pleural cavity. These included bed rest and surgical procedures employed to reduce overall lung size. .Although bed rest seemed beneficial for individuals in the early stages of their disease, advanced cases of tuberculosis were less likely to respond and death often resulted.
The modern era of treatment began in 1946 with the introduction of streptonmycin. Its effect on pulmonary disease was dramatic, and even more dramatic was the discovery that patients with miliary and meningeal disease, conditions that previously had almost always been fatal, recovered. However, by 1952, it had become apparent that treatment with at least two drugs (streptomycin and p-aminosalicylic acid) was necessary in order to avoid drug resistance. Also in 1952, a much more effective drug, isoniazid, was discovered. As a result, tuberculosis became curable for the first time in the majority of patients.
From 1952 to 1970, large-scale, cooperative trials established several essential criteria in the treatment of tuberculosis: that at least 18 months of continuous therapy was required; that pulmonary surgery was rarely if ever necessary; that bed rest did nothing to aid recovery; and that patients receiving chemotherapy quickly became noninfectious. With no scientific need for bed rest or isolation, sanatoria disappeared, and the treatment of tuberculosis came under the auspices of the general practitioner and the general hospital.
In the 1970s, the use of rifampin aided researchers in the development of combination regimens that required treatment for only six months, compared with previously established multidrug regimens that took 18 to 24 months.[18-20] Obviously, this shorter-term treatment protocol was a boon to treatment, resulting in enhanced patient compliance and a greater success rate.
Unfortunately, however, the efficacy, low cost and ease of administration popularized the idea of treating not only active cases, but all people suspected of carrying the disease, based on a positive tuberculin test. Ironically, this en-chusiastic attempt at eradicating tuberculosis is partially responsible for the emergence of multidrug-resistant (MDR) strains. The proliferation of multidrug-resistant strains is directly related to the recent resurgence of tuberculosis, particularly among high-risk groups such as HIV patients. (See Table 1.) Tuberculosis also has become the sixth most common occupationally acquired infection among laboratory workers, estimated at 2 to 9 times greater than the general population.
Table 1 Populations at High Risk for Tuberculosis * People with HIV infection. * Close contacts and family members of people who have tuberculosis. * People with medical conditions that increase the risk of tuberculosis, such as transplant patients. * Foreign-born individuals from high prevalence countries. * Low-income populations, including high-risk minorities. * Alcoholics and intravenous drug users. * Residents of long-term care facilities, including nursing homes and correctional facilities.
Beginning in 1985, the decline in the incidence of tuberculosis reversed dramatically and began to increase for the first time in decades. Between 1985 and 1991, the Centers for Disease Control reported an 18.4% increase in reported cases.[22-26] (See Fig. 3.) The catalyst for this dramatic increase is attributed to the steady increase in the HIV-positive population and the reactivation of latent tuberculosis in these patients. In addition, large outbreaks of multidrug-resistant tuberculosis have occurred recently.[27-28]
Although outbreaks of drug-resistant tuberculosis are not uncommon and were reported soon after the first antimicrobial treatments were employed, outbreaks tended to be relatively localized and slow in development. However, recent outbreaks of multidrugresistant tuberculosis tend to involve patients in institutional settings such as hospitals, homeless shelters, long-term care or correctional facilities, and are much more rapid and virulent in the progression and spread of the disease.
During the period of 1990 to 1992, the Centers for Disease Control investigated six outbreaks of multidrug-resistant tuberculosis in hospitals.[27,29-31] The number of cases in each outbreak ranged from 5 to 65 patients. All of the outbreaks involved the transmission of Mycobacterium tuberculosis. In each case, DNA finger printing was used to corroborate transmission from one patient to another. Nearly all of the patients had organisms that were resistant to isoniazid and rifampin, the two most effective antituberculosis agents. Resistance to isoniazid and rifampin is serious in nature. The minimum duration of therapy must be extended for a period of up to 18 to 24 months and the cure rate is deceased. Mortality in these patients is extremely high, ranging between 72% and 89%, and is associated with rapid progression to death (median interval, 4 to 16 weeks).
In each outbreak, more than 80% of cases were reported in HIV-positive individuals. Development from infection to act*e tuberculosis is extremely virulent and rapid in HIV-infected individuals, occurring within weeks or months of infection.[32-34] Tuberculosis occurs relatively early in the course of AIDS, often preceding pneumocystis by several months or years.
Unfortunately, patient-to-patient transmission of tuberculosis often is unrecognized and underreported because of the delay between initial infection and progression to active symptoms and diagnosis. However, distinctive drug resistance patterns and the clustering of cases related to the extremely rapid progression to active disease in HIV-positive patients has enhanced recognition in certain outbreaks. Health care workers in attendance during these outbreaks are at increased risk of infection and many undergo seroconversion, presenting with positive tuberculin skin test results after exposure to patients with multidrug-resistant tuberculosis. In the aforementioned studies, at least eight HIV-positive health care workers developed active tuberculosis as a result of contact with infected patients, and four of the eight have since died from multidrug-resistant tuberculosis, underscoring the need for prompt and accurate diagnosis and effective prophylactic measures to prevent the spread of the disease.
There are several strains of tuberculosis; however, the two most important are the human and bovine strains. The mycobacteria are difficult to stain and grow slowly in vivo. Their cell walls contain a waxy substance that prevents ordinary staining methods from detecting the presence of the bacteria. A special staining process must be employed by heating a smear with strong carbolfuchsin (also known as Ziehl-Neelsen stain). Once this stain has penetrated the organism, it cannot easily be removed with acid or alcohol; hence, its designation as "acid-fast bacteria."
Mycobacterium is a slow-growing organism and tuberculosis is spread by airborne particles or droplet nuclei, infectious particles of respiratory secretions made airborne when infected individuals sneeze, cough, speak or sing.[36,37] The primary mode of infection is due to the inhalation of droplet nuclei. Particles are 1 [mu]m to 5 [mu]m in size. Normal air currents are sufficient to keep the droplets airborne for prolonged periods of time, facilitating the spread of particles throughout a room or building.[36,38] The majority of aerosolized tubercle bacilli are believed to die in transit; however, under experimental conditions of controlled temperature and humidity, the half-life of an aerosolized tubercle bacilli is about 6 hours. The probability of infection is proportional to the concentration of infectious droplets in the air and the volume of air breathed during exposure. Cough frequency also is associated with infectiousness.
Exposure in relatively small enclosed spaces, such as the naturally ventilated rooms where families live and workplaces without central ventilation, are probably the most important transmission settings. In larger buildings with central heating and air conditioning systems, forced-air ventilation is important in the transmission of tuberculosis. Forced-air ventilation recirculates infectious air, exposing all of the occupants to possible infection.
Infection occurs when a susceptible individual inhales droplet nuclei into the lungs. Once in the alveoli, the bacteria is ingested by alveolar macrophages, which are then modified to become epithelioid cells. These cells have more cytoplasm than typical macrophage and lose their ability to ingest material. The accumulation of epithelioid cells tends to be focal and small tubercles are formed. These tubercles are 0.5 mm to 1.0 mm in diameter and are just visible to the naked eye. Some of the epithelioid cells form giant cells of the Langerhans type, surrounding the mass of epithelioid cells. There also is a diffuse zone of lymphocytes with a few plasma cells and fibrocytes.
Within two weeks, necrosis begins in the mass of tissue containing not only the epithelioid cells but also those cells peculiar to the part involved. The necrosis is called caseation, and the dead tissue forms a dry, firm, coagulated mass, similar in view to cheese. Caseation is the result of hypersensitivity to the products of the bacilli. The end result is a fully formed tubercle consisting of a central mass of caseation surrounded by epithelioid cells and, occasionally, giant cells. This then is surrounded by a wide zone of round cells. Adjacent tubercles tend to fuse as the caseation process continues and wide areas of tissue are destroyed. Lesions now can be seen with the naked eye and caseation may extend for many centimeters. Progressive caceation is the hallmark of tuberculosis. In some cases the firm caseous tissue may undergo liquefaction. The resultant cavity is filled with pus teaming with bacilli. The pus tends to move in the direction of least resistance, extending the tuberculous lesion as it moves.
Tubercle bacilli also can spread via the lymph nodes, and in some cases spreads into the bloodstream, resulting in widespread dissemination of the bacteria. The infected individual becomes severely ill and often develops meningitis. This condition is called generalized miliary tuberculosis, derived from the appearance of many small tubercles throughout the body resembling tiny millet seeds. Generally, within 2 to 10 weeks after initial infection, the human immune response limits further multiplication and the spread of tubercle bacilli. This is known as primary (or childhood) tuberculosis. This term came into use in the early 20th century when radiographic observations revealed that infection in childhood was relatively common. Children's radiographs usually revealed large, often massive, mediastinal lymphadenopathy with an often inconspicuous area of pneumonitis in the lower or mid-lung field.
In some instances, however, bacilli can remain dormant for years, a condition known as latent tuberculosis infection. There is a 10% risk for the development of active tuberculosis, with the greatest risk during the two years post infection. These individuals have a positive tuberculin skin test but are not infectious.
Several known risk factors are involved in the progression from latent tuberculosis to active tuberculosis. This course of events is called reactivation (also known as postprimary or adult) tuberculosis, and radiographic findings usually indicate the presence of apical or subapical infiltrates, often with cavitation and no hilar adenopathy. The inference is that in adults, reactivation tuberculosis is the result of reinfection in a previously sensitized host, perpetuated by the belief that primary infection always had occurred by adolescence. This hypothesis is based in part on the Koch phenomenon -- the observation that the second inoculation in an already infected pig would produce marked local inflammation and necrosis, but the sharp limitation of the new inoculum.
Recent findings indicate that the clinical and radiographic difference has more to do with age-related immunity; however, differentiation between primary and reactivation tuberculosis has become more difficult in recent years. The successful treatment of tuberculosis and resultant public health measures have resulted in less exposure to tuberculosis during childhood, and today there is an increased incidence of first exposure in adulthood, resulting in a greater incidence of primary tuberculosis in adults.
Methods of Diagnosis
Occupational transmission of tuberculosis will remain a risk until accurate diagnosis of the disease can be made in hours instead of weeks. The tuberculin skin test, developed in the 1930s and relatively unchanged to this day, poses several problems. First, its results can be unpredictable and are often poorly understood, resulting in a significant number of false-positive and falsenegative results. Furthermore, a positive PPD (purified protein derivative of tuberculosis) is not always indicative of active infection. While a tuberculin test does not sensitize a previously uninfected individual, it can elicit a positive result. For example, previous vaccination with bacille Calmette-Guerin (BCG) can cause a boosted response that mimics the results of a new infection.
In a recent Canadian study, Menzies demonstrated that when compared with a nonvaccinated control group, a study group of individuals previously vaccinated with BCG were more likely to have a positive PPD test after two-step boosting. It can be inferred, therefore, that tuberculin skin test conversions among serially tested BCG-vaccinated employees may in large part represent boosted responses to previous BCG vaccination rather than new infection with Mycobacterium tuberculosis. Proper interpretation of the results can be difficult. At present, foreign-born, BCG-vaccinated health care-workers comprise a substantial portion of the health care work force, and in those who are serially tested, tuberculin skin test conversions may be the result of revaccination rather than new infection. This dilemma serves to confound the interpretation of infection control interventions. It also underscores the need to perform two-step testing, which is the confirmation of initial test results, with a second test performed at least one week later, to eliminate boosted responses to previous vaccination.
The booster effect can be prevented by retesting individuals who demonstrate a very small or negative tuberculin reaction. Most common in middle-aged and older patients, the booster effect develops within one week after testing and may last for up to a year or more. If the second test is positive, subclinical hypersensitivity due to a previous infection can be confirmed. A negative result to two tests given a week apart validates true negativity and does not magnify the risk for new infection in a previously unexposed individual.
Relatively unaltered from its inception, the PPD test is associated with false-negative results in as many as 20% of patients with known active tuberculosis. As Sepkowitz notes, "It is sobering to consider that, in the day of molecular epidemiology, the multimillion dollar tuberculosis control efforts of the next decade will be evaluated by the measurement of a tiny bump with a ruler scored in millimeters -- all to determine if someone is `anergic' or `allergic' to mycobacteria."
Prompt and accurate diagnosis is key to controlling the spread and treatment of tuberculosis. In fact, in addition to false-negative results obtained from the PPD test, as many as 50% of patients with active pulmonary tuberculosis also exhibit negative smears for AFB, further confounding an accurate diagnosis.
In the early 1950s, the number of cases of tuberculosis among health care workers at a Los Angeles city hospital decreased dramatically after the introduction of routine chest radiography of patients upon admission. This study underscored the significance of unsuspected cases of tuberculosis in the increased rate of infection among care givers. Delay in the diagnosis of tuberculosis can have grave consequences. In a Texas study, a lag in the diagnosis of tuberculosis in a patient with AIDS resulted in tuberculin conversion in 19% (30 of 158) of exposed staff members.[2,43] In a recent outbreak of tuberculosis in New York City, 34% of exposed employees underwent conversion for tuberculin skin testing. The highest rate of conversion occurred among employees caring for patients in the AIDS ward.[2,26,44]
Obviously, the consequences of admitting patients with undiagnosed tuberculosis is profound. One study involved the admission of 17 patients with unsuspected tuberculosis to a teaching hospital and found that staff members exposed to these patients (median time between admission and isolation, five days) were significantly more likely to test positive for tuberculosis than nonexposed employees. Interesting by comparison, during the same time period, 51 patients initially suspected of having tuberculosis and treated accordingly were not associated with any tuberculin skin-test conversions among their attending staff.[2,44,45]
It has been suggested that HIV patients with tuberculosis are more infectious and more likely to cause nosocomial spread than their non-HIV counterparts.[45,46] A study by DiPerri et al reported higher rates of tuberculosis among employees working with HIV patients with tuberculosis than with HIV-negative patients with tuberculosis.[2,47] However, other studies suggest that HIV-positive patients with tuberculosis are in fact less contagious. More clinical trials are needed to settle this issue.
The Role of Radiography In the Detection of Tuberculosis
The radiologic technologist plays an integral role in the diagnosis of tuberculosis and the fight to eradicate this disease. The emergence of the AIDS epidemic has dimmed any chance of halting the global spread of tuberculosis in the near future. The incidence of tuberculosis in patients with AIDS is 500 times that of the general population. This increased susceptibility in HIV-positive individuals may be explained by their impaired immune function. Occupational-exposure to HIV-positive patients, the homeless and other high-risk groups pose an increased risk of transmission to the health care professional. However, the risk of occupational transmission of tuberculosis can be eliminated only when prompt and accurate diagnosis is combined with appropriate chemotherapeutic intervention.
Traditional Chest Radiography
Controversy exists whether traditional chest radiography has the sensitivity and specificity required of an effective screening device for the detection of active tuberculosis in patients with AIDS. In patients with HIV, primary tuberculosis may not appear with the usual radiographic abnormalities. Although the reactivation of dormant foci or reinfection are the primary causes of active tuberculosis in HIV-positive patients, chest radiographs will be more consistent with primary or childhood tuberculosis. Even with the caveat that all parenchymal, pleural or mediastinal abnormalities be considered indicative of active tuberculosis, a large percentage of this increasing population will go undetected using standard chest radiographs alone. In fact, more than 50% of HIV-positive patients with active tuberculosis, based on positive sputum smears for AFB, will be classified as disease free based upon their radiographic results alone. (See Fig.4.)
Conventional and High-resolution Computed Tomography
Computed tomography is considered by many to be the method of choice to eliminate or confirm a suspected diagnosis of active tuberculosis. Primary tuberculosis often is accompanied by lobar pneumonia with radiologically recognizable enlargement of the lymph nodes in the hilium or mediastinum. The site of primary tuberculosis in the lungs reflects areas of greatest ventilation, most commonly the middle or lower lobes or the anterior portion of an upper lobe.[50,51]
The typical presentation of primary tuberculosis on =CT scan is air-space consolidation. The consolidation usually is homogeneous, dense and well defined.[49,51] It generally is confined to a segment or a lobe. However, as the disease progresses, particularly in immunocompromised or diabetic patients, lobar or segmental pneumonia may break down into multiple cavities. (See Fig. 5.) Primary tuberculosis appears as a solitary cavitary lesion in about 10% of cases. Acute bronchospread of tuberculosis can occur from the breakdown of a lobar infection or from the rupture of an infected lymph node into the bronchus. The disease then spreads widely to other bronchi or other lobes.
In patients with miliary tuberculosis, early chest radiographs may appear normal. Follow-up radiographs may reveal a poorly defined haze throughout the lungs. Typical nodules of 1 mm to 2 mm become recognizable later in the course of the disease. Eventually, as the disease progresses, miliary lesions consolidate and cavitation may occur. A high resolution CT scan, however, can reveal poorly or well-defined nodules throughout the lungs. (See Fig. 6.)
Many patients do not require a CT scan to confirm the diagnosis of tuberculosis. It can be used to identify or confirm the presence of artifacts that may confirm the diagnosis of tuberculosis when radiographic findings are normal or inconclusive, but symptoms are suggestive of tuberculosis. Computed tomography also is useful in the detection of miliary tuberculosis in patients with fever of unknown origin and in whom chest radiography is normal. CT, particularly high-resolution CT, is superior to chest radiography for assessing tubercular activity. Certain findings including parenchymal lesions with centrilobular branching linear structure, centrilobular or centribronchiolar nodules, acinar shadows and large lobular consolidations are considered indicative of active disease. Cavitary lesions, consider-ed the most significant radiologic evidence of active disease, are well depicted on CT scans.
Magnetic Resonance Imaging
Improved soft tissue contrast, multiplanar capabilities, intrinsic flow sensitivity and lack of ionizing radiation should make magnetic resonance imaging an ideal thoracic imaging modality. Theoretically, the increased soft tissue contrast on MRI should allow more accurate differentiation of pathology in the lungs. However, its application in the lung has been limited by signal loss due to physiologic motion and the unique combination of air and soft tissue that constitutes the inflated lung.
The strong external magnetic field of an MRI scanner interacts with the hydrogen nuclei within water and fat molecules in the patient. En general, failure to accurately visualize lung tissue is due to the large difference in magnetic susceptibility between air and soft tissue.[56,57] Motion of water or blood during the imaging sequence also modifies the detected signal and cannot be adequately assessed with conventional MR sequencing. To accommodate for this, a projection reconstruction algorithm similar to that used in CT scans is employed. This technique provides improved visualization but accentuates physiologic motion. In addition, the projection reconstruction technique is highly susceptible to magnetic field inhomogeneity, which leads to a blurring of the reconstructed image.
At present, MRI remains a secondary imaging modality to chest CT in detecting pulmonary tuberculosis. MRI techniques that minimize the effect of physiologic motion and compensate for the magnetic field inhomogeneity of the inflated lung are in development and are anticipated to become more important in the diagnosis of tuberculosis by the late 1990s.
Compared with traditional radiography, CT and MRI may provide enhanced diagnostic capabilities in the detection of extrapulmonary tuberculosis and the extent of the disease. Extrapulmonary tuberculosis is tubercular involvement of any organ outside the lung. It includes disseminated disease and bacteria, pleural disease and thoracic disease. It can occur with or without the presence of pulmonary involvement. The course of the disease can be acute and rapid or slow and chronic, and any organ may be involved. Clinical findings often mimic other diseases and result in delay and misdiagnosis. In fact, between 20% and 50% of cases of extrapulmonary tuberculosis are diagnosed at autopsy only.[60-64]
Historically, extrapulmonary tuberculosis primarily afflicted children and decreased in incidence with age, until the incidence peaked again in the elderly population. Today, groups at particular risk for the development of extrapulmonary tuberculosis include HIV-positive patients with low CD4+ cell counts; patients with immunosuppression, chronic renal disease and hemodialysis; bone marrow transplant patients and jejunoileal bypass patients.[65,66] Pregnancy also may be a risk factor. As many as two-thirds of HIV-patients infected with tuberculosis may have extrapulmonary involvement. Multiple sites of infection are common in AIDS patients, and bacilli may be found in lymph nodes, blood, bone marrow, urinary tract, liver, gastrointestinal tract, the central nervous system, cardiovascular system, skin and soft tissues.[68-70] Skeletal tuberculosis, in which the spine is most commonly involved, represents approximately 3% of all cases of tuberculosis and 30% of cases of extrapulmonary tuberculosis.[71-73] (See Fig. 7.)
Diagnosis of extrapulmonary tuberculosis is difficult and may be facilitated with the use of MRI. While traditional radiography remains a primary diagnostic tool in the detection of extrapulmonary tuberculosis, CT and MRI can help identify the extent of the disease, as well as identify disease in a symptomatic patient with normal radiographs.
Preventing the Spread of Mycobacterium tuberculosis in the Health Care Setting
Controlling the spread of tuberculosis in an institutional setting can be difficult. Several factors contribute to this crisis, including patient noncompliance with prescribed drug regimens, which can lead to the development of multidrug-resistant bacterium from drug-susceptible strains; increased exposure of institutionalized patients or employees to patients with active tuberculosis; inadequate infection control practices and lack of isolation facilities.
A key component in limiting the spread of tuberculosis is prompt and accurate diagnosis. Because sputum analyses, radiographic findings and latent infection can delay diagnosis and treatment, there has been a corresponding slow reaction toward implementing proper control procedures that has contributed to a proliferation of the disease. Prolonged exposure to undiagnosed patients with multidrug-resistant strains of tuberculosis is directly related to the present proliferation in reported cases.
Second only in importance to accurate diagnosis and implementation of proper isolation procedures, appropriate chemotherapeutic intervention is critical. Compliance in patients with drug-susceptible tuberculosis is key in curtailing the development of drug-resistant tuberculosis. Patients must understand the potential hazards of deviating from their prescribed drug regimens. Due to the long-term and complex nature of the drug treatment involved, patient education is essential to achieve proper compliance. Ideally, observed therapy, a technique in which the patient is observed taking his or her medications by appropriate medical personnel, is the method of choice.[75,76]
Another vital step in reducing the number of outbreaks is adherence to the 1994 CDC Guidelines for Preventing the Transmission of Tuberculosis in Health-Care Facilities. The guidelines outline specific procedures and levels of intervention to be implemented depending upon the risk of transmission in a particular setting. [See Fig. 8.)
They also underscore the tenet that an effective tuberculosis control program requires early identification, isolation and effective treatment of patients with active tuberculosis. Such a program also must develop policies and procedures for control of tuberculosis that undergo periodic review and evaluation to determine their effectiveness.
The CDC guidelines underscore the need for a hierarchical approach to the prevention and control of outbreaks of tuberculosis among health care workers. The first level of hierarchy involves the use of administrative measures designed to prevent the exposure of uninfected individuals to infected patients. This encompasses several different components:
* The development of procedures to rapidly identify, isolate and treat infected individuals.
* The implementation of effective work practices to minimize exposure to the bacterium, such as the mandatory use of respiratory protection with suspected or confirmed cases, adherence to proper isolation techniques and appropriate use of air filtration systems.
* Continued education, training and counseling of health care workers about tuberculosis.
* Routine screening of health care workers for infection and disease.
The second level of the hierarchy details the use of engineering procedures to prevent the spread and reduce the concentration of droplet nuclei, which includes the use of a direct source of control using local exhaust, controlling the airflow to prevent spread of infectious droplets to adjacent areas, diluting and removing contaminated air, and air cleaning via air filtration or ultraviolet germicidal irradiation.
The goal of the recommendations as outlined in the first two levels of the hierarchy is to reduce the risk of spread of Mycobacterium tuberculosis within the institutional setting; however, these measures do not reduce the risk of spread in areas where occupational exposure to patients with tuberculosis may occur, including hospital sleeping rooms, treatment areas such as the radiology department, areas in which cough-inducing or aerosol-generating procedures are performed or isolation areas.
The third level of hierarchy involves the use of personal respiratory protection equipment to reduce exposure in areas were exposure may occur. Because exposure can occur when entering these areas of treatment or isolation, the use of personal respiratory protective equipment is strongly recommended. It is important to note that information regarding the smallest infectious dose of Mycobacterium tuberculosis has not been identified, although there is evidence that infection can be caused by a single tubercle bacilli deposited in the lung. Furthermore, the concentration of viable droplet nuclei that may be expelled by infectious patients is not known, and accurate measures to determine the level of infectiousness are not available. As a result, administrative controls and engineering measures may not adequately protect health care workers in instances where the risk of exposure is high.
Appropriate use of respiratory protective devices is essential when there is high risk of exposure to infectious patients. It is vital that protective respirators meet Occupational Safety and Health Administration (OSHA) respiratory protection standards and that the equipment be certified by the National Institute of Occupational Safety and Health (NIOSH).
The CDC makes several recommendations that are essential in tuberculosis infection control in the health care setting. These recommendations include:
Assignment of Responsibility
Responsibility for the tuberculosis infection program should fall under the auspices of a person or group of people with expertise in infection control, occupational health and engineering. This group should be given the authority to implement appropriate control procedures.
Tuberculosis control measures should be based on the risk of transmission of tuberculosis in a particular setting. A baseline measure should be undertaken to evaluate the risk of transmission in each area or department of the facility. All outpatient facilities should be evaluated for risk as well.
Identification, Evaluation and Initiation of Treatment For Patients Suspected of Having Active Tuberculosis
Protocols must be developed, implemented and enforced for the prompt identification of patients with tuberculosis. Diagnostic measures must be carried out in patients in whom active tuberculosis is suspected. These include a complete medical history, physical exam, PPD skin test, chest radiograph, microscopic examination and culture of sputum, and other diagnostic procedures when appropriate. Prompt laboratory results are crucial.
Patients with confirmed or highly suspected active TB should be started immediately on an anti-tuberculosis drug regimen. Inpatients should be directly observed taking their medications to ensure compliance. Drug susceptibility testing should be undertaken to confirm the efficacy of prescribed treatment protocol.
Management of Patients Who May Have Active TB In Ambulatory-Care &stings and Emergency Departments
Early identification and isolation of patients with suspected cases of active tuberculosis is essential. Triage in emergency rooms and ambulatory-care settings should involve formal methods for the prompt identification of these patients. Health care workers who are the primary contacts in these settings should be trainee to identify possible cases of active tuberculosis by observation and direct line of questioning. The goal is to minimize the time spent in an open area. In suspected cases, tuberculosis precautions should be implemented immediately. These include isolating the patient as soon as possible, providing the patient with a surgical mask and instructions to keep the mask on, supplying tissues to the patient and explaining that they must use the tissues to cover their nose and mouth when sneezing or coughing.
In some instances, an unconscious patient without overt signs or symptoms of tuberculosis may present in the emergency room. Some of these patients may belong to one or more high-risk groups for tuberculosis, such as homelessness or evidence suggestive of alcohol or substance abuse. These patients should be managed using standard tuberculosis precautionary measures, such as the use of surgical masks by attendant health care workers and observance of isolation procedures until a diagnosis of tuberculosis can be ruled out.
In ambulatory-care settings, such as health care clinics, care should be taken to prevent contact between patients with tuberculosis and HIV-positive patients or other immunocompromised patients. This can be accomplished by designating certain times of the day for appointments with patients with active tuberculosis. Proper ventilation in waiting rooms and examination rooms should be designed and maintained to reduce the risk of transmission.
In facilities where patients with tuberculosis are frequently seen, isolation rooms should be available. In facilities where contact with patients with tuberculosis is infrequent, isolation rooms are not required but written protocols should be developed for the prompt identification of these patients, including detailed instructions for their transfer to an area of isolation or a collaborating facility.
Equipment used on patients with tuberculosis usually is not involved in the transmission of the disease, although transmission due to the use of contaminated bronchoscopes has been demonstrated.[80,81] The CDC offers guidelines for the decontamination, cleaning, disinfection and sterilization of patient-care equipment.[36,82,83]
Patient-care equipment is divided into three categories: critical care items, semicritical items and noncritical items.[84,85] Critical items are instruments introduced directly into the bloodstream or into other normally sterile areas of the body, such as needles, surgical equipment and catheters. These items should he sterile when used. Semicritical items are instruments that may come in contact with mucous membranes but do not ordinarily penetrate bodily surfaces, such as fiberoptic endoscopes, bronchoscopes and endotracheal tubes. Although sterilization of these items is preferred, high-level disinfection is acceptable. Fastidious cleaning of these items prior to sterilization or disinfection is critical.
Noncritical items are those that do not ordinarily touch the patient or only touch the patient's skin, such as blood pressure cuffs, x-ray equipment, crutches, bed boards and certain other medical items. These items are not associated with direct transmission of Mycobactenum tuberculosis, and washing them with detergent generally is sufficient.
Decontamination procedures should be based on the equipment used, not on the diagnosis of the patient. Selection of appropriate disinfectant agents also depends on the intended use of the equipment, the level of disinfection required and the nature of the item to be disinfected.
Microorganisms found on walls, floors and other environmental surfaces rarely are associated with the transmission of tuberculosis to patients or health care workers. Because infection with tuberculosis is dependent on the inhalation of airborne particles, extraordinary attempts to disinfect or sterilize environmental surfaces are not indicated. In general, cleaning-with an EPA-approved germicide/disinfectant that is not tuberculocidal is appropriate.
The same daily cleaning procedures used in other patient rooms should be used to clean tuberculosis isolation rooms; however, health care workers should observe isolation room precautions when cleaning these rooms. Once the patient has been discharged, final cleaning of the isolation room can be performed without personal protective equipment provided the room has been ventilated for the appropriate length of time.
Management of Hospitalized Patients Who Have-Confirmed or Suspected Tuberculosis
In the hospital setting, any patient with known or suspected active tuberculosis should be placed in an isolation room that meets CDC ventilation recommendations. Each health care institution should provide its employees with written policies regarding indications for isolation, isolation practices to be followed, persons authorized to-initiate and discontinue isolation, management of uncooperative patients and criteria for rescinding isolation.
Isolation rooms should be single-patient rooms with appropriate ventilation equipment. An isolation room should be maintained under negative pressure to prevent the spread of droplet nuclei. Current recommendations from the CDC are that the air be changed six times per hour in isolation and treatment rooms. Air from these rooms should be exhausted outside in accordance with applicable federal, state and local ordinances.
Like adults, children diagnosed with tuberculosis should be isolated until they are no longer infectious. Family members should be evaluated for infection for tuberculosis and be required to wear a surgical mask outside of the child's room until infectiousness has been ruled out.
Isolated patients should be counseled and educated about their disease, the need for isolation and the importance of compliance with their prescribed drug regimen. Patients should be instructed to keep their doors closed and to use a tissue to cover their nose and mouth when sneezing or coughing.
When possible, all diagnostic procedures should be performed in the patient's room to avoid possible transmission of the disease. When patients must be moved out of isolation for essential medical procedures, the patient should wear a surgical mask and the procedures should be performed at a time of the day when waiting and exposure to other patients can he kept at a minimum.
Ideally, in facilities where there is a high incidence of tuberculosis, radiology departments should have a separate, ventilated area for examination. When this is not possible, patients should wear a surgical mask and be returned to isolation as soon as possible.
All health care workers who must enter an isolation room should wear respiratory protection. Likewise, visitors should be supplied with respirators and given instructions regarding proper use.
Education and Training of Health Care Workers
All health care workers should be educated about tuberculosis. The program should include information about the etiology of Mycobacterium tuberculosis, its transmission, the need for prompt diagnosis, the difference between latent and active tuberculosis, signs and symptoms and potential for reinfection. Isolation procedures should be discussed and protocols established to prevent contamination. The importance of routine PPD skin testing and its significance should be discussed. It is vital that health care workers report any PPD skin test conversions and seek medical evaluation if symptoms associated with tuberculosis present.
The higher risk for developing tuberculosis in HIV-positive or other immunocompromised employees should be reviewed, including the rapid development from infection to active tuberculosis, differences in clinical presentation and the high mortality rate associated with multidrug-resistant tuberculosis in this population.
Any health care worker who has a persistent cough lasting longer than three weeks should be screened for tuberculosis. In addition, other symptoms such as weight loss, night sweats, bloody sputum, anorexia or fever should be promptly evaluated. The employee should not return to work until the diagnosis has been excluded or treatment is begun and the health care professional is no longer infectious.
Screening for tuberculosis in health care workers should be performed periodically in accordance with the risk assessment for a particular facility. In facilities with very little risk, recommendations for screening are variable, whereas in facilities considered to be high risk, screening is recommended every three months.
Coordination with the Public Health Department
Patients with suspected or confirmed cases of TB must be reported to the public health department so appropriate follow up and a community-contact investigation can be arranged. A detailed and written discharge plan coordinated with the patient, health department and medical facility should be implemented. Patient confidentiality should be protected in accordance with state and local laws. Results of all AFB-positive sputum smears, positive cultures for Mycobacterium tuberculosis and susceptibility results should be reported to the public health department as soon as they are available.
The public health department also can help plan and coordinate tuberculosis-control programs, including screening, surveillance and outbreak investigations.
Strategies for Controlling Tuberculosis
The continued resurgence of tuberculosis is attributed to myriad factors: increased exposure and inadequate access to appropriate medical care for proper diagnosis and treatment; poverty; homelessness; overcrowding in institutions; substance abuse; immigration from areas where tuberculosis is prevalent; and infection with HIV.
Globally, tuberculosis is the leading cause of death from any single infectious agent. It is estimated that there are 8million new cases and 3 million deaths from the disease each year. It is responsible for approximately 7% of all deaths and about 26% of preventable deaths in the world, most of these deaths occurring among young adults.
At present, one-third of the world's population is infected with tuberculosis and it is-the most common infection related to infection with HIV. In New York City alone, the largest urban site of infection in the United States, between 600,000 and 1 million people are infected with tuberculosis, and approximately 40% of those patients also are infected with HIV. To further confound matters, multidrug-resistant tuberculosis is found in nearly 20% of New Yorkers with active disease. At present, the reported rate of tuberculosis in New York is five times higher than the national average.
Recent statistics indicate that HIV-negative patients with tuberculosis have a 10% chance of developing active disease in their lifetime. By contrast, the risk of developing active tuberculosis in HIV-positive patients also infected with tuberculosis is 10% per year. In fact, the risk of progression from infection to active disease in HIV-positive patients is so substantial that pulmonary tuberculosis was included on a list of AIDS-defining diseases issued in 1993 by the CDC.
In the early 1980s, medical experts told Congress that tuberculosis could be eradicated in the United States before the turn of the century at an estimated cost of $30 million. However, the long-standing decline in the number of reported cases of active tuberculosis encouraged experts to endorse relaxed health care policies based on predictions that tuberculosis could be eradicated by the year 2010. Ironically, Congress has recently been asked to approve $540 million in funding just to control the emerging epidemic.
As David E. Rogers, M.D., of Cornell Medical University in New York, stated during his presentation at a recent World Congress on Tuberculosis, "The opportunity to eliminate one of humankind's most persistent scourges has been lost and we are paying dearly for it."
The decades-long decline of tuberculosis ended in the mid-1980s, but not before complacency and overconfidence in its control by the government and medical community led to the dismantling of proven, effective public health strategies. Resultant funding cuts directly undermined a public health infrastructure that had been carefully developed over time for the surveillance and treatment of tuberculosis, including reporting requirements, publicly sponsored tuberculosis clinics and residential facilities where noncompliant patients could be monitored as a last resort.
Lack of access to medical care, shortened hospital stays, inadequate ventilation procedures, reduction in social welfare programs and the resultant growth-in poverty and homelessness, the increased numbers of people in institutionalized settings like correctional facilities, shelters, nursing homes, and an increase in migrant workers and immigrants have contributed to the rise in tuberculosis.[90-92]
In addition, the proliferation of cases of drug-resistant tuberculosis that can be attributed to poor compliance is an outgrowth of insufficient medical and social infrastructure. Poor compliance with prescribed drug regimens has long been a source of concern, particularly with the development of multidrug-resistant strains of tuberculosis. Recently, the issue has resurfaced regarding the possible need for coercive measures to ensure that patients comply with their prescribed drug regimens.[86,90,92] This issue has become extremely complex when attempting to quantify the risk that a patient with active tuberculosis imposes on uninfected individuals. A pending lawsuit Mixon vs New York), predicated on the Americans with Disabilities Act, seeks to establish the rights of AIDS patients who live in homeless shelters to require that the city provide them with free or low-cost housing as individuals or small groups because of the high risk of infection with tuberculosis that exists in shelters.
Experts advocate the proven, cost-effective policy of administering directly observed therapy to patients with tuberculosis.[86,90-95] The American Lung Association, American Academy of Pediatrics, Infectious Disease Society of America and Centers for Disease Control and Prevention published a statement titled "Control of Tuberculosis in the United States" in which they make the recommendation that physicians adopt a high index of suspicion for tuberculosis among children and adults in high risk groups. Limited access to health care for individuals at high risk, however, may undermine the effectiveness of this mandate.
Prompt and accurate diagnosis and effective treatment remain the key to the effective control and eradication of tuberculosis. Numerous strategies have been discussed to prevent the transmission of tuberculosis, ranging from routine screening of high-risk populations to incarceration of criminally noncompliant individuais.[86,90.92] Multidrug-resistant tuberculosis is an artifact of noncompliance and ineffective prescribed drug regimens.[86,94] Directly observed therapy is a much heralded, cost-effective technique to encourage compliance, and it is certainly preferable to involuntary confinement.[86,90,92]
All 50 states have laws in effect to control the spread of infectious disease, including tuberculosis. Many of these statutes are based on antiquated laws that predate modern concepts of constitutional law. As a result, they are undergoing revision to ensure that respect for human rights are ensured while protecting public health. Currently, 38 states require their public health departments to provide free testing for patients who cannot pay for it themselves, and also to cover the costs of inpatient treatment for patients with active tuberculosis. To date, only six states cover the cost of home care.
The future of tuberculosis control must focus on two primary goals:
* Development of strategies to ensure the prompt diagnosis and treatment of infected individuals.
* Formal procedures to ensure compliance.
These procedures should provide incentives, social support, education, counseling, drug treatment, housing and employment programs. Coercion and involuntary confinement will continue to be necessary for a minority of patients whose behavior threatens the public health. For these individuals, patient rights must be protected while observing due process of the law.[90,92]
The dramatic resurgence of tuberculosis is a public health emergency that will have profound effects on our society in the future. The social and economic toll exacted by tuberculosis is tremendous, particularly with the proliferation of multidrug-resistant strains of Mycobacterium tuberculosis. Keys to controlling this epidemic are prompt and accurate diagnosis, isolation and efficacious treatment. Radiologic technologists play an important role in helping to identify this disease and prevent its spread.
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