Mr. Scheel is a MD/PhD student at the University of California­San Diego, CA. Dr. Sartoris is deceased.

The World Health Organization estimates that approximately one-third of the world's population is infected with tuberculosis (TB). TB kills 3 million people each year and accounts for more than 25% of preventable deaths in adults. Approximately 1% of the world's population is infected with TB each year, resulting in more deaths than malaria and AIDS combined. It is estimated that by 2020, another 1 billion people will be infected with TB, leading to 70 million deaths. ¹

With the advent of antituberculous drugs 50 years ago, cases of TB steadily declined until 1985, when the human immunodeficiency virus (HIV) emerged as a global infectious disease. ² HIV and TB pandemics, acting synergistically, have proven to be a lethal combination. ³ In most healthy individuals, the immune system effectively attenuates the initial TB lung infection and prevents the spread of the disease to extrapulmonary locations. The TB bacilli can lie dormant in the lungs for many years until the host's immune system is weakened, as in elderly patients and HIV-positive patients. In fact, extra-pulmonary TB infections in patients with HIV is an AIDS-defining illness. ^4,5 It is estimated that one-third of the TB cases over the last 5 years can be attributed to HIV. Of the estimated 31 million people infected with HIV, 30% to 40% also have TB, making it the greatest killer of HIV patients. ^5,6 There has also been a rise in nontuberculosis mycobacterium among HIV patients. Another cause of the increase in the number of TB cases is an increase in foreign-born immigrants, accounting for half of TB cases in industrialized nations. ⁷

Particularly disturbing has been the increasing frequency of multiple drug-resistant tuberculosis (MDRTB) isolated from infected individuals. MDRTB is defined as tuberculosis isolates having resistance to both isoniazid (INH) and rifampin (RMP). In HIV-negative patients, these infections are infrequent, and are almost always the result of an irregular drug supply, inappropriate prescription, or patient noncompliance. In patients who are HIV-positive, MDRTB has also emerged as the result of inadequate treatment; however, its spread to close-contacts has increased in frequency at a more alarming rate than in non-infected individuals. MDRTB cases have already exceeded 4% of clinical isolates in large cities such as New York, NY; Newark, NJ; Dallas, TX; Oakland, CA; and Sacramento, CA. In patients with HIV and MDRTB, the mortality rates are 70% to 90% within months of infection; however, in patients with HIV and drug-susceptible TB, case-fatality rates are similar to those of other infections. ⁸

In 1994, the International Union Against Tuberculosis and Lung Disease (IUATLD) began a global project on MDRTB surveillance in order to measure its prevalence in several countries. During this study, 50,000 TB cases from 35 countries, representing 20% of the world's population, were studied. Each study evaluated resistance against INH, RMP, ethambutol (EMB), and streptomycin (SM) as well as whether the drug resistance was primary or acquired. Primary drug resistance is defined as strains that were resistant prior to drug treatment. The mean prevalence of MDRTB in this category was 1.4%, ranging from 0% in Kenya to 14.4% in Latvia. Kenya was the only country studied that did not have a case of MDRTB. Acquired drug resistant strains originate from case mismanagement; i.e., from patient noncompliance or insufficient drug therapy. This category had a much higher mean prevalence at 13%, ranging from 0% in Kenya to 54% in Latvia. ⁹ Individual countries have reported similar findings.

Clinical presentation

The clinical presentation of a dual HIV and TB infection may be different from either of their individual symptomologies. With increasing numbers of these two diseases in industrialized nations, physicians need to be aware of how TB presents itself in immunocompromised patients. In a patient not infected with HIV, TB presents itself with general systemic signs and symptoms such as weight loss, night sweats, fever, malaise, and anorexia, as well as signs and symptoms specific to the site of infection. In the presence of HIV, the clinical presentation depends on the status of the patient's immune system. Many of the signs and symptoms of HIV resemble those of TB, making it difficult to make an accurate diagnosis. Usually, in patients initially infected with HIV, pulmonary TB denotes stage 3 of the HIV infection and extrapulmonary TB denotes stage 4.

Mycobacterium tuberculosis primarily infects the thoracic (figure 1) and lumbar vertebrae (figure 2) and weight-bearing joints (figures 3 and 4); however, it may involve any bone (figure 5), joint, tendon, bursa or fluid-containing structure (figure 6). ⁴ Approximately 10% to 15% of osteoarticular tuberculosis is multifocal (figure 7), and in rare instances, aseptic-appearing polyarthritis is associated with extra-articular TB. This condition is believed by some to be Poncet's disease, a reactive arthritis, because it responds to anti-TB therapy. ^10,11

Imaging of tuberculosis

Radiology is still the most cost-effective test for TB, and provides the most important information required for making a diagnosis of spinal TB (figure 8). Radiography provides the definitive proof of a TB infection, allowing the physician to begin chemotherapeutic treatment immediately. In spinal cord cases, radiography effectively shows the narrowing of the vertebral disc spaces and involvement of the vertebral body (figure 9), eventually leading to an anteriorly directed collapse with secondary kyphosis (figure 10).

CT and MRI are most useful in the preoperative evaluation of patients requiring surgical treatment for TB, but are also more accurate than plain radiography in showing vertebral involvement. The anterior, posterior, and lateral soft-tissue features of spinal infections were delineated equally with both. However, because the coronal and sagittal planes can be obtained directly without loss of spatial resolution, MRI is better at visualizing the extent of the infection.

Lateral CT scans are helpful in diagnosing spinal TB in areas of the thoracic spine obscured by vertebral bodies. Axial CT is also optimal for depicting posterior bony abnormalities, such as pedicle lesions.

Although both MRI and CT scans depict the extent of spinal cord compressions equally, T1-weighted MRI is superior in its ability to show the nature of the damage. MRI can also show the preserved spinal tissue being compressed into the remaining vertebral body in some cases. In a study by Hoffman et al, ¹² MRI was performed on 11 paraplegic patients with TB and showed that pus and granulation tissue from TB was the main cause of the spinal cord compression in 8 of these patients. Resolution of the compression and neurological lesions were also shown with MRI after 4 months of chemotherapy. Additionally, sagittal MRI was determined to be the best method for visualizing the severity and nature of the extradural compressions and a useful way to differentiate an abscess from fibrous tissue. ¹³

Multiplanar MRI provides the most accurate demonstration of a TB infection in the spinal cord, including extent of injury and the spread of debris from the site of infection. The site of tissue injury appears as a decrease in signal intensity on T2-weighted images. This technique has been useful in the description of the pathological tissue responsible for spinal cord compression by allowing physicians to visualize liquid pus on T2-weighted images. ¹² A worse outcome is indicated in patients with focal myelopathy in the spinal cord, documented on T2-weighted images as discrete abnormal lesions. Prolonged cord compression with resultant ischemia has been observed in patients with a delayed presentation, severe kyphosis, and marked neurological deficits. AR

Acknowledgments

The authors wish to thank G. Puri for her critical evaluation of this paper. J.R. Scheel is supported by Research Fellowship F31 NS108060 from the National Institutes of Neurological Disorders and Strokes.

References

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