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
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
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
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.”