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Letter
Pulmonary Tuberculosis and
SARS, China
Wei Liu,* Arnaud Fontanet,† Pan-He Zhang,* Lin Zhan,* Zhong-Tao Xin,‡
Fang Tang,* Laurence Baril,† and Wu-Chun Cao*
*Beijing Institute of Microbiology and Epidemiology, Beijing, People's
Republic of China, †Institut Pasteur, Paris, France; and ‡Beijing Institute
of Basic Medical Sciences, Beijing, People's Republic of China
Suggested
citation for this article
To the Editor: As part of a cohort study of 83 patients with severe
acute respiratory syndrome (SARS) in Beijing, China, we conducted a follow-up
study of all the patients by routine medical examination. During the process,
3 patients with chest radiographs consistent with active disease were
identified as having pulmonary tuberculosis (TB). Here we describe the
1-year clinical outcome and immune response in these patients.
Demographic details and coexisting conditions are shown in the Table.
Patient 1 was a healthcare worker who became infected with SARS-associated
coronavirus (CoV) while on duty with SARS patients. After he was transferred
to a hospital dedicated to SARS management, pulmonary TB was diagnosed
(positive acid-fast bacilli smear on sputum samples). Patients 2 and 3
were known to have cases of pulmonary TB and became infected with SARS-CoV
after contact with other patients hospitalized for SARS. These 2 patients
were sputum smear–negative for acid-fast bacilli, and diagnosis was made
on the basis of previous exposure to TB, relevant symptoms of typical
pulmonary TB, chest radiographs consistent with active disease, a positive
tuberculin skin test result, and the finding of cavity regression on chest
radiographs after anti-TB treatment was initiated. No cultures were obtained
for isolation and comparison of Mycobacterium tuberculosis strains
(1). All 3 patients had confirmed SARS based on
amplification of SARS-CoV RNA by reverse transcriptase–polymerase chain
reaction (RT-PCR) from sputum and stool specimens (2).
Patients 2 and 3 recovered without complications; patient 1 had the most
severe disease and required mechanical ventilation in an intensive care
unit before recovering.
Both cellular and humoral immunity were evaluated during the follow-up
of these patients. T-lymphocyte subsets were measured 6 months after disease
onset by flow cytometry using fluorescein isothiocyanate–labeled specific
monoclonal antibodies. Compared to other SARS patients (n = 47), the 3
patients with TB had lower mean CD4+ T cells (368.4/μL vs. 656.6/μL,
respectively; p = 0.05) and lower mean CD8+ T cells (371.0/μL vs. 490.1/μL,
respectively; p = 0.39). SARS-CoV immunoglobulin G (IgG) antibody titers
were measured by enzyme-linked immunosorbent assay kit (Huada Company,
Beijing, China) at months 1, 2, 3, 4, 7, 10, and 16 after disease onset.
(Titers were not measured for the 3 TB patients at month l.) Compared
to most (26 [78.8%] of 33) other SARS patients whose antibodies remained
detectable throughout follow-up, 2 of the 3 TB patients (patients 1 and
3) had undetectable antibody titers as of months 7 and 16, respectively.
In patient 1, antibody titers, when detectable, were unusually low (40).
Both patients 1 and 3 had prolonged viral excretion in stools, sputum,
or both. While the median (range) duration of virus excretion in stools
and sputa for the entire measurable cohort (n = 56) was 27 (16–127) and
21 (14–52) days, respectively (3), it was 125
and 16 days for patient 1, and 109 and 52 days for patient 3 (viral excretion
data could not be obtained from patient 2 because sequential specimens
for detection were unavailable).
TB in SARS patients has been reported on rare occasions (4,5).
In a cohort of 236 patients in Singapore, it was diagnosed in 2 patients
after recovery from SARS (4). As with patient
1 in this study, TB had developed after the patient acquired SARS, most
likely as the result of reactivation of past infection or new infection
with M. tuberculosis, while temporarily immunosuppressed because
of SARS (6) and corticoid therapy. Such phenomena
have been described with other viral infections such as measles and HIV
(7,8). By contrast, patients 2 and 3 were known
TB patients who acquired SARS through exposure to SARS patients in the
same hospital wards. Both diseases are known to be transiently immunosuppressive
(6,9), and their combined effect resulted in more
pronounced CD4+ cell decreases in coinfected SARS patients than others.
Such immunosuppression also resulted in poorer IgG antibody response in
coinfected SARS patients than in others and delayed viral clearance, as
shown by longer viral excretion in sputum and stools. While viral excretion
could be prolonged in coinfected patients, no virus could be isolated
from any RT-PCR–positive specimen collected after 6 weeks of illness,
which suggests that excreted viruses were no longer infectious (3).
These case reports remind us of the importance of strict isolation of
SARS patients, careful use of steroids for their case management, and
the possibility of coinfection with TB in SARS patients with incomplete
recovery.
This work was partly
supported by the Programme de Recherche en Réseaux Franco-Chinois (P2R),
the EC grant EPISARS (SP22-CT-2004-511063, SP22-CT-2004-003824), the
National Institutes of Health CIPRA Project (NIH U19 AI51915), and the
National 863 Program of China (2003AA208406, 2003AA208412C).
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Table. Demographic and
clinical information on severe acute respiratory syndrome (SARS)
patients with pulmonary tuberculosis (TB), Beijing, China, 2003
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Demographic/clinical characteristic
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Patient 1
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Patient 2
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Patient 3
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Sex
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M
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M
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M
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Age (y)
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48
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18
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20
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Other coexisting conditions
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Pseudomonas aeruginosa infection
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None
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None
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Date of SARS onset
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Apr 5, 2003
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Apr 7, 2003
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Apr 4, 2003
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Date of TB diagnosis
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Jun 12, 2003
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Jan 24, 2003
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Mar 5, 2003
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Date of hospitalization or transfer to SARS ward
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Apr 7, 2003
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Apr 7, 2003
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Apr 5, 2003
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Leukocyte count at admission, /μL
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12,500
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6,800
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2,500
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Total steroid dose used, mg
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25,280
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2,600
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3,600
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Intensive care unit admission
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Yes
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No
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No
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CD4/CD8 cell ratio 6 mo after disease
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0.63
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1.56
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1.23
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Absolute CD4 cell count 6 mo after disease, /μL
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368
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431
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306
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Absolute lymphocyte count 6 mo after disease, /μL
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2,098
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1,115
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1,666
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Suggested citation
for this article:
Liu W, Fontanet A,
Zhang P-H, Zhan L, Xin Z-T, Tang F, et al. Pulmonary tuberculosis and
SARS, China [letter]. Emerg Infect Dis [serial on the Internet]. 2006
Apr [date cited]. Available from http://www.cdc.gov/ncidod/EID/vol12no04/05-0264.htm
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