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COVER ARTICLE/CME Urgent Care 2(4):16, 2007 Public health officials tell us that tuberculosis (TB) rates in the United States have decreased for both native-born and foreign-born individuals over the past decade. However, the decrease among foreign-born persons is less substantial, and more than half of all TB cases diagnosed in the United States in 2005 were in this group. Although TB kills nearly two million people worldwide every year, most physicians in this country have not had to deal with the disease on an everyday basis. But with the occurrence of several outbreaks of multi-drug-resistant TB and the need for new treatment regimens, as well as the increase in the number of unauthorized aliens entering this country who do not undergo immigrant screening, it is important to keep TB in mind as a potential cause of illness, especially in foreign-born persons presenting to urgent care settings. In this article, we will discuss two case presentations of TB and review recent updates in the epidemiology, diagnosis, treatment, and prevention of the disease. CASE PRESENTATION #1 A 21-year-old Honduran man is brought to an urgent care facility in southern California by U.S. Customs and Border Patrol agents. After being apprehended for illegal entry into the United States, he told the agents he felt ill. On presentation to the facility, he complains of generalized weakness, fever, and a nonproductive cough of one week’s duration. Over the previous three weeks, he had traveled from his home in Honduras through Mexico and had spent the past 10 days in communal housing near the U.S. border. He is otherwise healthy, with no significant medical or surgical history. He takes no medications and doesn’t smoke or use illicit drugs. He says he drinks beer occasionally. A review of systems is significant for subjective weight loss due to decreased food intake while traveling. He is one of four children, and his parents are laborers in Honduras. The patient’s vital signs are: temperature, 98.8°F; heart rate, 70; blood pressure, 128/68; respiratory rate, 18. Pulse oximetry reveals an oxygen saturation of 98% on room air. The physical exam finds a well-developed male with no lymphadenopathy; the HEENT exam is unremarkable. His lungs are clear on auscultation bilaterally with good air movement; his heart has a regular rate and rhythm with no murmurs, rubs, gallops, or clicks; and his abdomen is soft and nontender, with no hepatomegaly, masses, or rebound tenderness. The extremity exam is unremarkable, as are the skin, musculoskeletal, neurologic, and psychological exams. Laboratory testing reveals a normal complete blood cell count and normal electrolyte levels. However, a chest x-ray demonstrates right lower lobe cavitation and consolidation (see image below).
CASE PRESENTATION #2 A 34-year-old Chinese immigrant presents to an emergency department with a three-month history of persistent cough with bloody sputum, intermittent fever, nocturnal diaphoresis, and a 15-pound weight loss over the previous month. He reports that he was released two months ago from a prison in China after serving a five-year sentence for theft. While in prison he developed pneumonia and was started on “some drugs.” The patient reports that he does not know the type of infection he had or the medications that were used to treat him, but says that “they made me take them every day for two years and sometimes changed one of the medications when my cough got worse.” He states that the prison housed hundreds of inmates, many of whom were ill with similar symptoms, and that he knew of at least 20 persons on his cell block who died during the five years he was there. He describes the prison as “very crowded,” with minimum food rations and little medical care. The patient denies any other medical problems and reports only one surgery for a left arm fracture after an altercation in the prison. He says his only medications are ibuprofen and a Chinese herbal tea for his cough. He is an only child, and his mother and father are farmers with no significant medical conditions. He has a 50-pack-per-year history of cigarette smoking but denies alcohol abuse or illegal drug use. His vital signs are: temperature, 101.3°F; heart rate, 102; blood pressure, 142/88; respiratory rate, 24. He is 5 ft 4 in. tall and weighs 113 lbs. Examination reveals a cachectic, ill-appearing man in mild respiratory distress with episodes of coughing. He is oriented to person, place, and time. The HEENT exam is unremarkable. Auscultation of lung fields reveals rales, dullness with decreased fremitus, and whispered pectoriloquy prominent on the right lower base. A chest x-ray finds bilateral apical infiltrates (see image below).
The cardiac examination demonstrates mild tachycardia and a normal rhythm with no murmurs. His abdomen is thin, with normal bowel sounds in all four quadrants, and soft to palpation, with no palpable masses and no hepatosplenomegaly. Skin, musculoskeletal, neurologic, and psychological exams are all normal. ACTIVE TUBERCULOSIS ASSUMED Based on their histories, clinical presentations, and physical exam findings, as well as the abnormal chest radiographs, these patients must be assumed to have active TB disease until proven otherwise. In fact, it would have been prudent to place a surgical mask on them before completion of the history or physical exam. (Alternatively, when possible and if patient confidentiality can be maintained, the history interview may be conducted outdoors, away from open windows or areas where people tend to gather.) The primary mode of transmission of TB is by droplet nuclei produced by coughing, sneezing, or, in the case of laryngeal TB, vocalizations. The airborne particles can remain suspended for hours in a closed room with minimal air circulation. Therefore, it is extremely important to place the patient in respiratory isolation, particularly if he is coughing or a cavitary chest x-ray is noted, and preferably in an airborne infectious isolation (AII) room, formerly known as a negative-pressure isolation room. If this type of room is not available in an urgent care facility, then a surgical mask (not an N95 mask), as indicated above, should be placed on the patient and he should be admitted directly to the nearest hospital that has an AII room. The recommended airflow rate for an AII room is 12 or more air exchanges per hour, and the air should be either exhausted directly to the outside of the building or recirculated through a high-efficiency particle absorption (HEPA) filter. ETIOLOGY OF TUBERCULOSIS Tuberculosis is a communicable disease that is caused by Mycobacterium tuberculosis, or the tubercle bacillus. Mycobacterium tuberculosis and three very closely related mycobacterial species—M. bovis, M. africanum, and M. microti—can cause tuberculous disease, and collectively they compose what is known as the M. tuberculosis complex. It should be noted that M. bovis and M. africanum are rare causes of TB in the United States. In addition, M. microti does not cause TB in humans. As noted above, the disease is spread by very minute airborne particles expelled by an individual who has infectious TB. If there is another individual close by who inhales air containing these airborne particles, or droplet nuclei, transmission may occur. On inhalation, some of the bacilli may reach the alveoli, where they are most likely to be ingested by macrophages. The infection truly begins when the bacilli multiply inside these macrophages. When the macrophages die, the bacilli spread throughout the lymphatic channels to the regional nodes and then through the bloodstream to more distant organs, such as the brain, kidneys, and lungs, and into the skeletal system. The immune system response in an otherwise healthy individual will contain the bacilli and prevent development of the disease, often leaving behind a granuloma in the process. At this stage, however, the person has TB infection, which can be detected by the tuberculin skin test. It may take 3 to 12 weeks for an infected individual to develop a positive reaction to the skin test. Individuals who are infected with M. tuberculosis but do not have TB disease are asymptomatic and not infectious to other people, but they usually have a positive reaction to the skin test. Thus, TB infection in a person who does not have the active form of the disease is not considered a case of TB and is referred to as latent TB infection (LTBI). Approximately 10% of infected individuals will go on to develop active TB at some time, but the risk is considerably higher for individuals who are immunosuppressed, especially those with HIV. The majority of TB cases (about 73%) are pulmonary, but the disease can occur at almost any site in the body or as a disseminated disease. HOPES FOR ERADICATION With the introduction of anti-TB medication in 1948, there was great hope that TB would soon be eradicated in the United States. There was indeed a steady decrease in the incidence of TB from 1953 through 1984, with the number of reported cases declining by an average of 5.6% per year, from a high of 84,000 cases in 1953 to 22,255 cases in 1984. However, after nearly three decades of steady decline, the number of reported cases of TB rose by nearly 20% from 1985 to 1992. The major factors that contributed to this increase were a deterioration of the TB public health infrastructure, the HIV/AIDS epidemic, illegal drug use, an increased number of immigrants from countries where TB is common, and transmission of TB in close quarters, such as correctional and health care facilities and homeless shelters. The patient presented in the second case was a recent immigrant from China, a country that is second only to India in the number of TB cases. Persons who have been incarcerated, as was this patient, are also at greater risk for acquiring multi-drug-resistant TB. In the United States, the higher rate of TB in states and counties bordering Mexico reflects the influence of cross-border spread of the disease, as illustrated by the first patient presented. The good news is that since 1993, the number of reported TB cases has again declined, and the 14,097 cases reported to the Centers for Disease Control and Prevention (CDC) in 2005 represented a 2.9% decrease from 2004 and a 47% decrease from 1992. Still, while the overall number of TB cases is decreasing, cases continue to be reported in every state. Surveillance data have shown that TB in the United States affects racial and ethnic minorities disproportionately. Resistance to anti-TB drugs in reported TB cases continues to be a serious public health concern. Efforts to control TB through prompt identification and treatment will dramatically reduce the number of newly infected individuals added to this population. DIFFERENTIAL DIAGNOSIS AND TESTING In both patients presented above, one must consider multi-drug-resistant TB, community-acquired pneumonia, lung abscess due to Aspergillus or aspiration pneumonia, lung cancer, undiagnosed HIV with Pneumocystis carinii pneumonia, and infection with gram-negative bacilli (such as Fusobacterium), gram-positive organisms (such as Actinomyces), protozoa, and worm-associated lung infections. Both patients were admitted to an AII room and appropriate infection control measures were implemented. Posteroanterior (PA) radiographs revealed abnormalities consistent with TB. Sputum samples were sent for acid-fast bacilli (AFB) smears and culture and returned positive in both cases. The images below show an example of a positive acid-fast stain (see "Positive for TB" image, below) and growth of M. tuberculosis on Lowenstein-Jensen medium (see "Growth of Mycobacterium tuberculosis" image, below). A positive AFB smear is associated with a higher disease burden; however, a negative AFB smear does not preclude active disease. Hemoglobin and hematocrit values were within normal ranges despite reported episodes of hemoptysis in both patients. The QuantiFERON-TB Gold Test was used in place of the standard Mantoux tuberculin skin test (or purified protein derivative test) and was found to be positive for M. tuberculosis infection. In most U.S. populations, targeted testing for TB is done to identify persons who are infected and would benefit from therapy. Testing falls into two categories: individuals at higher risk for TB exposure or infection (see "Tuberculosis Exposure or Infection" box, below) and individuals at higher risk for active TB once infected (see "Active Tuberculosis in Infected Patients" box, below).
The traditional method of testing for TB infection is the aforementioned Mantoux tuberculin skin test. A positive Mantoux skin test requires a chest x-ray to look for pulmonary TB. In some settings, testing for TB with a chest x-ray or sputum sample may be more appropriate, especially in an urgent care clinic, where the patient may not return for follow-up. Urgent care physicians should be able to identify patients who are in a high-risk category and should administer TB skin tests to those patients as part of a routine workup. A patient’s reaction to a tuberculin skin test should be observed within 48 to 72 hours after the injection. Only the area of induration should be measured in millimeters and recorded. A measurement of 5 mm is considered a positive test result in HIV-positive individuals, recent contacts of TB cases, patients who have undergone organ transplantation or are immunosuppressed, and patients with fibrotic changes on chest x-ray. A measurement of 10 mm is classified as positive in recent arrivals from countries with a high TB prevalence, users of injectable drugs, residents and employees of high-risk settings, laboratory personnel, children under four years of age, and children exposed to adults in high-risk populations. A measurement of 15 mm is considered positive in individuals with no known risk factors for TB. A false-positive skin test can result from non-TB mycobacteria or the bacille Calmette-Guérin vaccination. A false-negative test may be caused by anergy, recent TB infection, live virus vaccine, or overwhelming TB disease. CONSTELLATION OF FINDINGS Symptoms of pulmonary TB include a constellation of findings, such as a prolonged cough, chest pain, fever, chills, night sweats, loss of appetite, weight loss, fatigue, and back pain. However, about 19% of TB cases occur outside the pulmonary system, and the symptoms of extrapulmonary TB depend on the site affected. A thorough physical examination is essential, but it can neither confirm nor rule out TB. It will, however, provide valuable information as to the overall health of the patient and will influence the treatment. A PA chest x-ray is the standard view used for the detection and description of chest abnormalities. In some instances, other views are needed, as well as computed tomography scans. In pulmonary TB, x-ray abnormalities are often seen in the apical and posterior segments of the upper lobes or in the superior segments of the lower lobes. Pulmonary cavitation is highly suggestive of contagious TB and prompt implementation of infection control measures should be considered to reduce staff exposure until this diagnosis can be ruled out. Keep in mind, though, that lesions can appear anywhere in the lungs and may differ in size, shape, density, and cavitation. Patients suspected of having pulmonary TB should have at least three sputum specimens taken 8 to 24 hours apart, with at least one sample collected in the early morning and examined by smear and culture. Detection of AFB in stained smears examined microscopically may provide bacteriologic evidence of TB. Smear examination permits only the presumed diagnosis of TB, because the AFB in a smear may be due to mycobacteria other than M. tuberculosis. However, cultures that are positive for M. tuberculosis confirm the diagnosis of TB. TREATMENT OF LATENT AND ACTIVE TB Prior to treating LTBI, active TB needs to be ruled out by culture and clinical diagnosis. In addition, the presence of radiographic abnormalities suspicious for TB requires sputum evaluation and further workup. Due to reports of severe liver injury and deaths, the CDC now recommends that the combination of rifampin and pyrazinamide should generally not be offered for treatment of LTBI. Appropriate treatment options using isoniazid and rifampin as monotherapy are given in the table (below). (A word of caution: Peripheral neuropathy has been associated with the use of isoniazid, so it is important to monitor for that complication in patients receiving that drug and to monitor liver function test results.)
For most patients, the preferred regimen for treatment of active TB consists of an initial two-month phase involving four drugs: isoniazid, rifampin, pyrazinamide, and ethambutol, followed by a four-month continuation phase of isoniazid and rifampin. Because of the relatively high proportion of adult patients with TB caused by organisms that are resistant to isoniazid, the four drugs are necessary in the initial phase for the six-month regimen to be maximally effective. Also, because treatment and monitoring will require follow-up beyond the urgent care setting, we recommend careful review of the drug tables in the CDC’s Treatment of Tuberculosis Guidelines (see Suggested Reading). Drug-resistant TB is transmitted in the same way as drug-susceptible TB. Findings indicate that drug-resistant TB is no less infectious than drug-susceptible TB, although the prolonged periods of infectiousness that can occur in patients with the former condition can often facilitate transmission. Multi-drug-resistant TB is disease that is resistant to both isoniazid and rifampin. Extreme drug-resistant TB is disease that is resistant to both isoniazid and rifampin and also resistant to any fluoroquinolone and at least one injectable second-line drug such as amikacin, kanamycin, or capreomycin. For culture-positive, drug-susceptible TB, there are four combination regimens that are recommended as initial therapies, involving the same four drugs mentioned above. These treatment protocols are based on clinical trial evidence and a rating system developed by the U.S. Public Health Service in conjunction with the Infectious Disease Society of America. The treatment protocols are also based on patient-centered care, utilizing both the private sector and public health departments to ensure proper diagnostic, therapeutic, and results monitoring for a comprehensive management plan focused on directly observed therapy. Based on the histories, examinations, and clinical laboratory results, the patients in both cases presented here were diagnosed with active TB. In the second case, the probability of multi-drug-resistant TB is extremely high in light of the following: presumed treatment failure over a two-year period while the patient was in prison, the reported single-drug changes to the treatment regimens, the frequency of multi-drug-resistant TB in China, and the prevalence of the condition in correctional facilities worldwide. Therefore, in a case like this, it is highly recommended that an infectious disease specialist or a physician specializing in the treatment of multi-drug-resistant TB be consulted prior to initiation of therapy. Also, working in conjunction with the local public health department, the treatment plan should be individualized to ensure proper medical management for the patient and public health. Keep in mind that treatment should be initiated before smear or culture results are available if the suspicion of active TB is high or the patient is seriously ill. In addition, patient isolation and proper airborne respiratory precautions are essential to reduce the risk of exposure of hospital staff and other patients to this morbid and potentially fatal infectious disease. PREVENTIVE MEASURES IN HEALTH CARE FACILITIES Effective prevention of TB in health care facilities stands on three legs: administrative measures, environmental measures, and respiratory-protection controls. Administrative measures include implementing TB infection control plans, assignments, and teams; conducting risk assessment; and educating health care workers on disease prevention, transmission, and screening. Environmental measures include employing local exhaust devices such as hoods, tents, or booths, controlling the air flow in AII rooms, and using HEPA filters to clean the exhaust air. Respiratory-protection controls include implementing effective staff training and institutional protocols and educating patients on proper cough etiquette and respiratory hygiene. When working with patients with active TB, medical and support staff personnel should don particulate filter respirators that meet the certification standards of National Institute of Occupational Safety and Health and the CDC. These respiratory protective devices can be nonpowered N95, N99, R99, R100, P95, P99, or P100 filter masks, either disposable or nondisposable models. Since individual face sizes and shapes will determine the fitting characteristics of these masks, the CDC guidelines recommend that initial and periodic fit testing be performed by respiratory experts. CRITICAL ROLE State and local health departments have the primary responsibility for preventing and controlling TB. However, the role of the urgent care physician is critical in identifying patients who have TB and initiating treatment. As our immigrant population continues to grow and urgent care medicine continues to evolve, it is incumbent upon all of us to “Think TB.”
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