Baltimore Opera Company

Study Guide

La Bohème
The Bohemians

What is Tuberculosis?

Tuberculosis has plagued human beings for more than three millennia. For this reason, it is not surprising that many an operatic heroine has succumbed to this debilitating malady. Mimi in La Bohème , Antonia in Les Contes D'Hoffmann , Manon in both Puccini and Massenet versions, and of course Violetta in La Traviata are examples of characters for whom tuberculosis brings a lyrical, albeit tragic, end.

During the last decade, it was anticipated in the United States that rapidly declining rates of the disease, reflecting effective antibiotic treatment would relegate tuberculosis to a diagnostic afterthought. However, this has all changed with recent resurgence of tuberculosis within hospitals, and accounts of health workers dying of tuberculosis caused by multi-drug resistant organisms. This re-emergence of tuberculosis in a somewhat new form has occurred within the setting of patients with HIV infection, patients receiving steroid hormones, and in-patients undergoing cancer chemotherapy. These three groups become susceptible to tuberculosis because of suppressed natural immunity.

What is Tuberculosis? Tuberculosis is a chronic bacterial infection caused by the organism Mycobacterium tuberculosis . This bacterium is one of 30 well-characterized members of the genus Mycobacterium , along with its relative M. leprae , the agent that causes leprosy. Most of the other mycobacteria, however, do not cause human disease. M. tuberculosis is transmitted from person to person via the respiratory route. The initial entry of the tubercle bacillus into the lung usually elicits an acute inflammatory response, rarely noted and usually accompanied by few or no symptoms ("primary" tuberculosis). The bacteria are ingested by white blood cells fighting the disease and are transported to the regional lymph nodes. These TB organisms persist within lymph nodes for many years and are responsible for later "re-activation" tuberculosis, the chronic process with a number of signs and symptoms which may be simulated in opera, such as Mimi's persistent cough and Violetta's prescient comment when she gazes into the mirror– “O, qual pallor!” –“Oh, what a pallor ! ” Patients typically develop chronic cough and sputum production, that may be associated with streaks of blood, weight loss, fatigue, low grade fever, and sometimes drenching night sweats several times a week. Pulmonary tuberculosis pursues a progressive course, and 60% of patients will succumb over two to three years if untreated. As pulmonary tuberculosis progresses, the normal architecture of the lung is lost, leading to scar formation and increased difficulty in breathing. The destruction of lung tissue leads to the formation of pulmonary cavities, which can be a source of bleeding and are readily seen on x-ray examination. Tuberculosis can also involve a number of structures in the body in addition to the lung, including the covering of the lung (the pleura), leading to effusion of fluid surrounding the lung; involvement of the covering of the heart, the pericardium, which can cause fluid to collect around the heart to impair normal cardiac function. Tuberculosis may also seed the abdominal cavity wall, the peritoneum, associated with fluid formation, abdominal pain, and swelling. Tuberculosis can also involve a number of other sites, including the skeleton, the kidneys, covering of the brain (menenges) and the eye. One of the celebrated locations of tuberculosis involvement is the adrenal gland, where destruction can lead to adrenal insufficiency, a potentially fatal disorder if not recognized and treated with steroid hormones.

A third form of TB is termed "miliary" tuberculosis, resulting from widespread dissemination via the blood stream (hematogenous dissemination). This process can involve almost any organ in the body and develops at the time of primary infection, so the infected patients have no antecedent history of TB. Lesions develop synchronously throughout the entire body, and patients become extremely ill in four to six weeks with fever, enlargement of the spleen, involvement of liver and multiple other organs.

In recent years tuberculosis has assumed a dramatically different clinical appearance as a major opportunistic infection occurring in immuno-comprised individuals, such as those who are HIV-infected. For such individuals who had a prior history of primary tuberculosis and subsequent HIV infection, the risk of developing tuberculosis is approximately 10% per year. When these infections are acquired in reverse order; however, the association is even more dramatic. Tuberculosis develops in as many as half of HIV-infected persons following primary infection with M. tuberculosis , and usually within a few months. The reason that this disease is so prevalent in this setting is that the white blood cell primary defense system of lymphocytes and monocytes, usually mustered to fight against tuberculosis infection, are destroyed by the HIV virus. Nearly half of AIDS patients with tuberculosis have extra -pulmonary forms of TB, including enlargement of lymph nodes in the neck. Among AIDS patients with pulmonary tuberculosis, many have an atypical X-ray picture also, with diffuse fine infiltrates and plural effusions that look more like a classical bacterial pneumonia. Moreover, there are some patients with sputum-positive tuberculosis whose X-rays can remain completely normal. Finally, there is a risk in the patient with AIDS also developing a related illness caused by the bacterium M. avium .

The diagnosis of Tuberculosis is established by identifying tubercle bacilli in sputum, urine, or body fluids. For the majority of patients who have tuberculosis in the lung, the diagnosis is established by microscopic examination of sputum and sputum culture. The chest X-ray is an important tool for diagnosis and evaluation. The classical picture of primary tuberculosis includes a calcified peripheral nodule with an associated calcified lymph node in the lung (the Ghon complex). Multiple nodules in the upper lobes and in the superior portions of the lower lobes form the typical picture of re-activation pulmonary TB. The familiar Tuberculin skin test is a reliable means for recognizing prior infection by M. tuberculosis . The test is executed with a purified and non-infectious protein from the M. tuberculosis bacterium. This causes redness and swelling in the forearm within 48 to 72 hours if the subject has had prior infection. Newer methods of rapid diagnosis are under development also, using detection of specific antibodies in the blood to tubercle antigens.

The contemporary treatment of tuberculosis is based upon the administration of combinations of effective anti-microbial agents. When appropriate chemotherapy is utilized, moreover, hospitalization, rest and improved diet are not thought to contribute to achieving cures. This contrasts with older, erroneous notions about the cause of tuberculosis. Prior to the identification of the tubercle bacillus, it was speculated that poverty and malnutrition were the actual causes of this disease, since it was identified primarily in lower socio-economic groups.

There are several efficacious treatment regimens, and these are capable of achieving a favorable outcome in 99% of patients. One effective regimen includes isoniazid and rifampin daily for nine to twelve months in a combined capsule. More recently, intensive therapy with isoniazid, rifampin, pyrazinamide, combined with either streptomycin of ethambutol, can result in remissions in six months. The major difficulty in tuberculosis therapy has been high patient default rates (40-60%). However, after appropriate treatment, relapses are less that 1%.

Prevention of re-activation tuberculosis later in tuberculin skin test-positive individuals can be largely accomplished by prophylaxis with isoniazid. An alternative approach has been to vaccinate individuals with an attenuated strain of the bovine (cattle) form of tuberculosis ( M . bovis ), that has been administered now to more than two billion persons. This vaccination is clearly safe, but its efficacy is controversial since it has offered little or no protection in some studies. However, because the disseminated form of tuberculosis, which has very high mortality among children, has been virtually eliminated, the continuing use of BCG vaccination in areas of high prevalence appears to be justified.

Dr. John Wilbur

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