Low CD4 cell count increases risk of severe forms of extra-pulmonary TB

Michael Carter
Published: 26 March 2012

A low CD4 cell count is associated with more severe forms of extra-pulmonary tuberculosis (TB), US investigators report in the online edition of Clinical Infectious Diseases. The mortality rate among patients with this form of disease was high.

“Among HIV-infected patients, severe forms of extra-pulmonary TB (central nervous system/meningeal and disseminated) were independently associated with CD4 cell counts less than 100,” comment the authors.

Incidence of TB has been falling in the US since 1993. But this has been accompanied by an increase in the proportion of cases which involve extra-pulmonary infection. This has been associated with the worsening of the country’s HIV epidemic.

Co-infection with HIV and specific sites of infection are risk factors for mortality in patients with extra-pulmonary TB.

Nevertheless, there are few surveillance data on the recent incidence of extra-pulmonary TB. Nor are the factors associated with outcome in HIV-positive patients with this form of disease well understood

Investigators in Atlanta therefore designed a retrospective study involving 320 patients diagnosed with extra-pulmonary TB at a large hospital between 1995 and 2007.

Their study had three aims: to describe the clinical presentation of extra-pulmonary TB; to establish which types of the disease were independently associated with HIV infection; and to see if CD4 cell count was associated with particular types of extra-pulmonary TB in HIV-positive patients.

The majority of patients with extra-pulmonary TB were male (68%), black (82%) and the median age was 38 years.

Almost half (48%) of the patients were HIV-positive. Only 13% of these HIV-infected patients were taking antiretroviral therapy. The overall mortality rate was 14%, but was significantly higher at 21% among the HIV-infected individuals. Few (3%) of the HIV-positive patients who died were taking antiretroviral therapy. 

The most common sites of extra-pulmonary disease were lymphatic (28%), meningeal (22%) and disseminated TB (28%). Patients with HIV were more likely to have central nervous system/meningeal TB (60%) or disseminated TB (58%) than HIV-negative individuals.

Overall 40% of patients had pulmonary disease as well as extra-pulmonary TB. Rates of pulmonary TB were higher among those with disseminated TB (63%) and pleural disease (49%).

A number of factors were independently associated with disease site.

HIV-positive patients were less likely to have pleural disease compared to lymphatic disease (AOR = 0.3; 95% CI, 0.2-0.6). Individuals with concomitant pulmonary TB were more likely to also have disseminated disease (AOR = 1.9; 95% CI, 1.3-2.8).

Analysis of the immune status of the HIV-positive patients showed that those with a CD4 cell count below 100 cells/mm3 were significantly more likely to have (AOR = 1.6; 95% CI, 1.0-2.4) a “severe” form of extra-pulmonary TB (central nervous system/meningitis or disseminated) compared to lymphatic TB.

“The relationship between lower CD4 and site of extra-pulmonary TB is consistent with presumed clinical pathogenesis to more severe forms,” note the authors. They suggest that early consideration of extra-pulmonary TB in severely immune-suppressed patients and the prompt initiation of anti-TB therapy could reduce the risk of mortality.

“Continuing to improve chronic HIV disease management and routinely keeping these severe forms of extra-pulmonary TB in clinical consideration are two means of improving outcomes for patients diagnosed with extra-pulmonary TB.”


Leeds IL et al. Site of extrapulmonary tuberculosis is associated with HIV infection. Clin Infect Dis, online edition: DOI: 10.1093/cid/cis303, 2012 (click here for the free abstract).

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