Low CD4 count is predictor of TB in patients with HIV
Low CD4 count is predictor of TB in patients with HIV
Study confirms findings of link to abnormal X-rays
A recent study of chest X-rays of HIV-positive patients confirms the importance of knowing the level of immunosuppression when evaluating for pulmonary tuberculosis. The lower the patient’s CD4 count, the more likely he or she will have atypical presentations of pulmonary TB, the study concludes.
"The message here is that you see less cavitation in HIV-positive patients, and you particularly see less of it in patients with low CD4 counts, and therefore don’t ever rule out TB if you are smart," says Richard Hafner, MD, medical officer for the National Institute of Allergy and Infectious Diseases and an author in the study published in the September issue of Clinical Infectious Diseases.1
David Perlman, MD, director of inpatient AIDS services at Beth Israel Medical Center in New York, explains to TB Monitor that this study reaffirms prior observations that the radiographic manifestations of HIV TB may be "atypical" that is, atypical for the adult reactivation TB seen in HIV uninfected people. The study also strengthens conclusions from other studies that the frequency of atypical manifestations (adenopathy, infiltrates) varies by CD4 count. Specifically, typical manifestations (cavitation) are seen more at higher CD4 counts while atypical features are seen at lower CD4 counts.
"In assessing the likelihood of TB in HIV-infected patients, the CXR [chest X-ray] pattern [often used to raise or lower the index of suspicion of TB] should be interpreted in the context of the patient’s CD4 count," he explains. "The other implication is that the pathophysiology of TB in HIV infected persons differs as a function of the degree of immunosuppression. The CXR findings at higher CD4s resemble those of reactivation TB in HIV-negative adults, perhaps suggesting that TB in HIV infected people is likely to be reactivation TB among those with higher CD4s."
In patients with lower CD4s, the patterns are atypical for reactivation, due possibly to reactivation of TB in a different manner than seen in HIV-negative patients. However, the patterns are actually "typical" for the CXR patterns seen in primary TB in children, he explains, adding that the finding implies that more of the TB seen among those patients may be due to recent transmission.
HIV-positive TB patients have been known to have cavitations in their lungs less frequently than HIV-negative patients and a higher frequency of adenopathy on chest X-rays. The reason for these differences has not been well established. Primary and reactivated TB also differ in radiologic presentations, and some researchers have argued that the atypical features of chest radiographs in HIV-positive patients may be attributed to the higher rate of primary TB among them.
To clarify the reasons, the study evaluated chest radiographic findings in a prospective multicenter treatment trial of HIV-related pulmonary TB. Baseline radiographs and CD4 counts were compared among 135 patients with culture-confirmed HIV-related TB. The study found that a large majority of patients 118 of 128 had abnormal radiographs that varied in manifestation dependent of their level of immunosuppression. Only seven patients with CD4 counts less than 200 had cavities, compared with 20 for those with CD4 counts greater than 200. The difference was statistically significant, Hafner says.
"The study showed that you were about three times less likely to see a cavitation if you have a patient who has CD4 counts less than 200," he adds.
The differences make sense when considering the normal course of TB infection, Hafner explains. In normal patients who have reactivated TB, their immune system usually is strong enough to fight the bugs, resulting in the inflammation and the formation of granulomas that appear as a cavity in the lungs. With immunocompromised patients, the inability to initiate an adequate response often results in abnormal radiographs.
Indeed, 10 of 128 patients had X-rays that showed no signs whatsoever of TB neither adenopathy nor infiltrates even though their sputum grew TB, Hasner notes. "This is a striking finding," he explains. "It means that in HIV-positive patients you can have very unimpressive to negative X-rays and still have pulmonary TB." The number of patients with normal X-rays was too small to detect a statistically significant relationship to their level of CD4 counts, he adds.
Typically, lymphadenopathy is unusual in patients with reactive TB. However, the study found that lymphadenopathy was found more frequently in HIV-positive patients than in HIV-negative patients, indicating that without a strong immune response, TB can spread more rapidly into the lungs and lymph nodes. Patients with CD4 counts less than 200 also experienced more cases of hilar/mediastinal lymphadenopathy evident in their X-ray (30%) than those whose had CD4 counts greater than 200 (7%).
"This means that if you see a lymphadenopathy in a patient with a low CD4 count, think TB," Hasner adds.
With the advance of viral load testing, the question is raised whether a patient’s viral load could be a predictor of abnormal X-rays in the same way CD4 counts are. Because CD4s and HIV RNAs are correlated, Perlman notes, one might predict that cavitary disease would be seen at lower HIV RNAs and adenopathy and infiltrates at higher HIV RNAs.
"That is just speculation," he says. "It could get complicated because active TB may increase the HIV RNA [through tumor necrosis factor or gamma interferon medicated increases in HIV replication] so the relationship may be confounded. I could not speculate as to a cutoff for HIV RNA."
Reference
1. Perlman D, El-Sadr W, Nelson E, et al. Variation of chest radiographic patterns in pulmonary tuberculosis by degree of HIV-related immunosuppression. Clinical Infectious Diseases 1997; 25:242-246.
Zuber PLF, Mckenna MT, Binkin NJ, et al. Long-term risk of tuberculosis among foreign-born persons in the United States. JAMA 1997; 278:304-307.
Describing the shifting epidemiologic profile of tuberculosis in the United States, the authors note that the increasing proportion of TB among foreign-born people may warrant new control approaches, despite four consecutive years of decline in overall disease.
The number of immigrants from countries with high prevalence of TB has continually increased during the last 15 years, they report, noting that as a result, the number of long-term residents with latent and active TB infection should rise in coming years.
"Detection of active cases among recent arrivals is the main priority in these populations, but many cases were in persons who arrived in the United States before the age of 35 years that could potentially have been avoided with preventive therapy," they conclude. "Elimination of TB in the United States may not be feasible using available diagnostic and treatment modalities without increased efforts to address the global burden of this disease."
The authors recommended that people younger than age 35 originating from countries with high TB prevalence be offered preventive therapy if they have a tuberculin skin test reaction of 10 mm or larger and no active TB. The highest risk of TB among long-term residents was observed in people from Vietnam, Haiti, the Philippines, and Korea.
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