Update in Tuberculosis and Nontuberculous
Mycobacterial Disease 2011
Payam Nahid1 and Dick Menzies2
1
Division of Pulmonary and Critical Care Medicine and Curry International Tuberculosis Center, University of California, San Francisco
at San Francisco General Hospital, San Francisco, California; and 2Respiratory Epidemiology Unit, Montreal Chest Institute, McGill University,
Montreal, Quebec, Canada
The number of tuberculosis (TB) cases and global TB incidence
rates is decreasing according to the latest World Health Organi-
zation Global Tuberculosis Report (1). This is very welcome news.
However, the 8.8 million incident cases of TB, 1.1 million deaths
from TB among HIV-negative people, the 350,000 deaths from HIV-
associated TB, and the millions of children orphaned as a result of
parental deaths caused by TB provide a stark reminder of the mag-
nitude of devastation caused by TB each year. Advances in under-
standing TB epidemiology diagnosis and treatment in 2011, many
of which were reported in the Journal, provide hope that the annual
decline in TB cases will accelerate.
EPIDEMIOLOGY OF TUBERCULOSIS AND LATENT
TUBERCULOSIS INFECTION
In many low- and middle-income countries, case notification in-
creased dramatically with the introduction of directly observed
treatment, short-course (DOTS), reflecting better access to ac-
curate diagnosis with high-quality smear microscopy and better
reporting (2). However, there is uncertainty regarding how
many cases remain undiagnosed. Van’t Hoog and colleagues
report on a massive community-based survey in Western Kenya
in which 20,710 participants completed questionnaires and un-
derwent chest X-rays and sputum examinations to determine
the prevalence of pulmonary tuberculosis (TB) (3). In total,
123 persons were detected to have smear and/or culture-
positive pulmonary TB. Of these, only six were currently on
TB therapy, although another 74 were on treatment but were
microbiologically negative. Of the 123 cases, 51% were HIV
infected; only 25% of these had been previously diagnosed.
If all those with chronic cough had been investigated, 70
(60%) of the 117 cases would have been detected. In total,
3,500 individuals reported chronic cough, meaning that only
2% of those with chronic cough had prevalent active TB and only
1% were smear positive. Combining chest X-ray and symptoms
could have identified all prevalent TB but would require screen-
ing 7,342 individuals, of whom only 0.6% were smear positive
and only 1.6% were culture positive. Hence, any strategy to en-
hance case detection will involve screening large numbers of
individuals. Further operational research is required to assess
the costs, feasibility, and benefits of such large-scale screening
programs.
Well executed prevalence surveys provide substantial infor-
mation, particularly when repeated to indicate temporal trends,
but are very expensive. It would be of interest to compare the
prevalence of active smear- and/or culture-positive pulmonary
(Received in original form March 18, 2012; accepted in final form April 30, 2012)
Correspondence and requests for reprints should be addressed to Payam Nahid,
M.D., M.P.H., University of California, San Francisco at San Francisco General
Hospital, San Francisco, CA 94110. E-mail: pnahid@ucsf.edu
Am J Respir Crit Care Med Vol 185, Iss. 12, pp 1266–1270, Jun 15, 2012
Copyright ª 2012 by the American Thoracic Society
DOI: 10.1164/rccm.201203-0494UP
Internet address: www.atsjournals.org
TB among immigration applicants to high-income countries
(who routinely undergo radiographic screening) with estimates
from large–scale, community-based prevalence surveys. Al-
though the absolute estimates among immigration applicants
may be different from a properly conducted community-based
survey, the applicant data are already gathered routinely by the
United States, Canada, and several other countries and may
provide insights into the epidemiology of TB and the impact
of TB control measures in many high-burden countries.
Another population-based approach to investigating TB is
demonstrated in a study by Brassard and colleagues, who used
health administrative databases from Quebec, Canada to inves-
tigate the association between prescription of inhaled corticoste-
roids and incidence of active TB (4). More than 99% of
Canadian residents are included in these health administrative
databases, reducing potential selection bias. Almost 500,000
individuals had received at least three prescriptions of any pul-
monary medication over 16 years; of these, 465 had active TB
(defined as at least two first-line TB drugs dispensed for at least
6 mo). Among individuals who did not receive oral corticoste-
roids, those who had received high-dose inhaled corticosteroids
(,1,000 mg/d of fluticasone or equivalent) had double the risk
of nonusers (adjusted relative risk, 1.97; 95% confidence inter-
val, 1.2–3.3).
There are limitations to this study that are common to all such
studies using health administrative databases. The most impor-
tant is that those who did not develop TB may not have had la-
tent TB infection (LTBI) because country of birth and other
markers of risk of TB infection were unknown. Because the ma-
jority of those who received inhaled corticosteroids were un-
likely to have had LTBI, they could not have developed
active TB, resulting in an underestimate of the potential impact
of inhaled corticosteroids. Nonetheless, this study adds to the ev-
idence that significant immune suppression can occur with use of
inhaled corticosteroids. The unequivocal benefits of inhaled cor-
ticosteroids in patients with severe asthma must be weighed
against the mounting evidence of increased risk of serious infec-
tious diseases.
Anandaiah provided an update of the epidemiology, pathogen-
esis, diagnosis, and treatment of HIV-TB (5). HIV accounts for
15% of global cases and 28% of TB-related deaths; these esti-
mates are approximately double those of 2006, reflecting better
awareness and testing for HIV coinfection. Highly active antire-
troviral therapy has dramatically improved survival; however,
because the risk of reactivation to active TB remains substantially
higher among HIV-coinfected individuals on highly active anti-
retroviral therapy than among HIV-uninfected individuals, it is
plausible that the total number of TB cases among HIV-infected
individuals may continue to increase. Smear microscopy is less
sensitive in HIV coinfected individuals but is enhanced with light-
emitting diode (LED) fluorescence microscopy, improved meth-
ods of sputum concentration, and sputum sample collection in
1 day (6). Hence, smear microscopy remains the primary method
of active TB diagnosis for resource-limited settings where the
feasibility of liquid cultures and nucleic acid application tests
Pulmonary, Sleep, and Critical Care Updates
(e.g., GeneXpert) is uncertain given their high costs. No trials
have demonstrated conclusively that treatment of active TB for
less than 6 months is adequate for HIV-infected persons. In fact,
some concern has been raised by recent systematic reviews (7)
and trials (8) that therapy should be routinely prolonged to
9 months to reduce rates of relapse, which are otherwise unac-
ceptably high in HIV-coinfected individuals.
Cost effectiveness analyses are useful to assess alternative
strategies when one strategy may be more effective but the al-
ternative is less costly. IFN-g release assays (IGRAs) are new
tests for the diagnosis of LTBI for which there is consistent
evidence of high specificity in all settings and populations.
There is also reasonably consistent evidence that IGRAs are
more costly. Linas and colleagues compared screening for LTBI
with tuberculin skin testing (TST) or IGRAs versus no screen-
ing in 19 different populations within the United States (9).
They found that screening of close contacts, HIV-infected indi-
viduals, and recent immigrants was very cost effective (using
a definition of cost less than $50,000 per quality-adjusted life
year [QALY] gained). IGRAs were more cost effective than
TST in all foreign-born populations, likely reflecting the impact
of BCG vaccination on TST specificity. TST was more cost
effective than IGRAs in contacts, HIV-infected individuals,
patients taking immune-suppressive medications, populations
with chronic medical conditions, and vulnerable groups such
as the homeless, former prisoners, or injection drug users. How-
ever, for the vulnerable groups (except for the homeless),
among those with chronic medical conditions and those taking
immune-suppressive medications, the incremental cost effec-
tiveness ratio was more than $100,000 per QALY gained for
TST and IGRs. Hence, screening with any test would not be
considered cost effective. Moreover, in all populations, the dif-
ference in QALYs was very small between the no-screening and
either screening strategy. Screening resulted in a gain (com-
pared with no screening) of more than 0.1 QALYs only for
contacts and HIV-infected individuals. Screening all foreign-
born or other populations with TST or IGRA resulted in
a net gain of less than 0.05 QALYs, which is equivalent to less
than 1 month gained.
This analysis highlights the two major limitations of current
LTBI screening and prevention strategies: (1) None of the cur-
rently available tests for LTBI can accurately predict who will
develop active TB. Hence, many persons must be treated to
prevent a single case. (2) The current standard treatment of
9 months of isoniazid (INH) has important toxicities, and com-
pletion rates averaged less than 50% in the studies cited by
Linas. Diagnostic tests that would better identify who will de-
velop TB, plus simpler and shorter treatments, such as the re-
cently reported 3-month, once weekly regimen of INH and
rifapentine (10), may make TB prevention more feasible, ac-
ceptable, and cost effective. The search for better tools for
LTBI must continue.
DIAGNOSIS OF TUBERCULOSIS AND LATENT
TB INFECTION
Worldwide, acid-fast bacilli (AFB) sputum smear microscopy is
the most widely used method for identifying TB cases. AFB spu-
tum smear microscopy is inexpensive and rapid, but it is insen-
sitive. In 2010, there were 5.7 million notifications of new and
recurrent cases of TB, equivalent to 65% (range, 63–68%) of
the estimated number of incident cases (1). Testing new strate-
gies to improve on smear microscopy is an important area of
research and an urgent priority for global TB control (11).
There are little data on adherence to international standards
for TB diagnosis and the quality of investigations of TB suspects.
1267
Davis and colleagues implemented an electronic, real-time per-
formance monitoring system at primary health care facilities in
five districts of Uganda to describe adherence to international
guidelines for TB suspect evaluation and TB case detection
(12). During the first quarter of 2009, clinicians ordered sputum
smear microscopy for only 21% of patients with cough for
2 weeks or more, and only 71% of patients with a positive
AFB sputum examination received TB treatment. These pro-
portions increased to 53 and 84%, respectively, in the fourth
quarter of 2009. The number of TB cases identified and pre-
scribed treatment increased from 5 to 21. These data suggest
that monitoring and evaluation can strengthen health systems in
low-income countries and can facilitate operational research on
the effectiveness and sustainability of interventions to improve
TB case detection.
Standard AFB smear microscopy involves collection of spu-
tum specimens on at least 2 days and examination of smears
using light microscopy. This approach is time consuming and
costly to patients who must make three visits to a health care
facility. As a result, up to 50% of patients fail to return to pro-
vide a second specimen or receive results. Cattamanchi and col-
leagues (6) compared the diagnostic accuracy of four case
detection strategies, specifically comparing one specimen ver-
sus two and traditional light microscopy versus LED fluores-
cence microscopy in 464 patients with cough for at least
2 weeks admitted to Mulago Hospital in Kampala, Uganda.
In total, 321 (69%) were HIV infected, and 232 (50%) patients
had culture-positive TB. LED fluorescence microscopy was
more sensitive than light microscopy with both the single-
specimen (61 vs. 55%) and two-specimen strategies (64 vs.
56%). Overall, there was no statistically significant difference
in sensitivity between the single-specimen and two-specimen
strategies when smears were examined with light microscopy
(55 vs. 56%) or LED fluorescence microscopy (61 vs. 64%).
Sensitivity was similar among the HIV-infected or uninfected
patients in the cohort.
The Xpert MTB/RIF Assay is an automated molecular-based
diagnostic developed for the GeneXpert platform (Cepheid, Sun-
nyvale, CA). This test has potential application as a rapid point of
care test for detection of Mycobacterium tuberculosis and rifampin
(RIF)-resistant TB. Several high-prevalence setting studies
prompted the WHO to endorse adoption of this test in 2010, with
more recent studies confirming the excellent performance charac-
teristics of the Xpert MTB/RIF assay (13–15). Questions remain
regarding implementation of the Xpert MTB/RIF assay in resource-
limited settings, including selection of patients to test, effects of
ambient conditions on diagnostic accuracy, and diagnostic per-
formance in paucibacillary disease as is often the case in chil-
dren, extrapulmonary TB and HIV-infected individuals. Theron
and colleagues used single archived spot sputum samples from
496 South African patients with suspected TB and found that
sample volume and sputum processing methods had a nonsignif-
icant impact on diagnostic performance of Xpert MTB/RIF
(16). Xpert MTB/RIF detected 95% (89 of 94) of culture-
positive TB cases with a specificity of 94% (320 of 339). Bacterial
load, indicated by smear grade and culture time-to-positivity,
correlated strongly with performance. For example, the sensi-
tivity in smear-negative cases was 55% (12 of 22). Relative to
smear microscopy, Xpert MTB/RIF detected an additional 33
cases (confirmed by culture or an alternative diagnostic method)
representing a 35% relative increase in the rapid TB case detec-
tion rate. However, sensitivity of Xpert MTB/RIF was lower in
HIV-infected compared with HIV-uninfected patients.
The Xpert MTB/RIF has quantitative capabilities reported as
threshold cycle (Ct) outputs that, if shown to correlate with bac-
terial burden, could provide measures of disease severity,
1268 AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
response to therapy, risk of transmission, and need for infection
control. Blakemore and colleagues (17) used 2008 samples along
with data collected from 741 patients enrolled in a previously
published multisite clinical trial (13) to compare Xpert MTB/
RIF assay quantitative output with results of direct and concen-
trated sputum smears, semiquantitative Lowenstein–Jensen
solid culture, and time-to-detection in liquid culture, with and
without adjustment for PCR inhibition measures. Decreasing
M. tuberculosis Ct was associated with increasing smear micros-
copy grade directly from sputum and concentrated sputum pellets.
A Ct cutoff of approximately 27.7 best predicted smear-positive
status. However, the association between M. tuberculosis Ct and
time-to-detection in liquid culture and semiquantitative colony
counts was weaker than smear. Despite a generally good correla-
tion, considerable variation was observed in the Xpert’s quantita-
tive estimate among sputum samples within the same acid-fast
bacilli grade. The authors noted that this observation could be
caused by variability within individual sputum samples, the inher-
ent inaccuracy of smear grading, or unexplained variation in the
Xpert MTB/RIF assay.
The notable advantages of newer molecular-based tests not-
withstanding, rapid and affordable culture-based techniques for
detection of TB and MDR-TB are still needed. The microscopic-
observation drug susceptibility (MODS) assay is a low-cost
method that could be useful to test large numbers of patients
in resource-limited settings where the cost of Xpert MTB/RIF
cartridges might be prohibitive. Shah and colleagues (18) eval-
uated the diagnostic accuracy of MODS among 534 consecu-
tively enrolled patients with TB at a district level hospital in
rural South Africa. Of these subjects, 388 (73%) were HIV
positive, with a median CD4 count of 161 cells/mm3. Median
turnaround time for MDR-TB diagnosis was 7 days (IQR, 6–9)
with MODS versus 70 days (IQR, 49–96) with an indirect pro-
portion method (P ¼ 0.001); this dramatic difference in time to
detection should translate to earlier appropriate treatment ini-
tiation. MODS test performance did not differ by HIV status,
with sensitivity of 88 versus 90% and specificity of 97 versus
100% for HIV positive versus HIV negative subjects, respec-
tively. Finally, the negative predictive values of 94 to 99% with
the MODS assay in this study suggest that this could be an
affordable option to rapidly exclude active TB in patients being
considered for isoniazid preventative therapy (IPT).
Another approach to excluding TB disease before initiation
of IPT is to rely on a symptom screen (19). The benefit of adding
a chest X-ray (CXR) to the screening process, as has been
advocated by the WHO is not known. Using data from the
Tuberculosis Prevention Program in Botswana, Samandari
and colleagues (20) conducted an analysis of the costs and
consequences (including death and isoniazid- and multidrug-
resistant TB) of adding CXR to symptom-based screening
activities in a hypothetical cohort of 10,000 HIV-infected indi-
viduals. A decision analytic model was used to compare a
‘‘Symptom only’’ policy against a ‘‘Symptom 1 CXR’’ policy.
They found that the “Symptom 1 CXR” policy prevented 16
isoniazid-resistant and 0.3 multidrug-resistant TB cases. How-
ever, as a consequence of attrition from the screening process,
there were 98 excess cases of TB, 15 excess deaths, and an addi-
tional cost of $127,100 for the cohort. The investigators found
that a CXR screening policy would only be beneficial when at-
trition was close to 0%. However, this would not be feasible or
affordable for resource-constrained countries such as Botswana
because elimination of attrition would cost $2.8 million per death
averted. These findings did not change in best- and worst-case
scenario analyses and suggest that IPT would exert its greatest
benefit when there is minimal attrition during the screening pro-
cess and more HIV-infected individuals receive treatment.
VOL 185 2012
No currently available test for LTBI provides a direct diag-
nosis of infection. Enthusiasm for IGRAs has been driven by
the enhanced specificity achieved by the use of antigens that
are more specific for M. tuberculosis than the antigens used
for the TST. However, the ability of IGRAs to predict those
who will progress to active disease remains poorly defined. Diel
and colleagues published an update of a cohort of close contacts
in Germany, expanding the study population to 1,335 close con-
tacts of smear-positive cases tested with both TST and IGRA
(QuantiFERON-TB Gold in-tube [QFT]; Cellestis Ltd, Aus-
tralia) and followed for up to 4 years to determine whether
active TB developed (21). They found that the IGRA results,
but not the TST results, were associated with duration of expo-
sure to an index case (P ¼ 0.0001). They also found that, despite
being close contacts of smear positive cases, an unexpectedly
high number of QFT-positive contacts (n ¼ 147) declined LTBI
treatment, among whom 19 developed active TB. The resultant
progression rate of close contacts who were QFT positive was
greater than that of the TST regardless of TST cutoff (12.9% for
QFT positives vs. 3.1% at a 5-mm cutoff and 4.8% at a 10-mm
cutoff). Of note, 28.6% (6 of 21) QFT-positive children devel-
oped active TB, which is significantly higher than the 10.3%
(13 of 126) QFT-positive adults (P ¼ 0.03). None of the 413
TST-positive, QFT-negative subjects progressed to active TB
disease over the course of follow-up. This study provides evi-
dence to suggest that QFT is more reliable than the TST for
predicting TB among close contacts in a low-incidence setting.
However, in a recent systematic review of this topic, in a subset
of five studies with 6,995 subjects that directly compared TST
and IGRA, the authors concluded that the abilities of IGRAs or
TST to predict active TB were “much the same” (22).
TREATMENT OF TB AND LATENT TB INFECTION
Shortening treatment for newly diagnosed active TB from the
current 6-month regimen to 3 or 4 months could benefit patients
and TB control programs by reducing default and enhancing
treatment success. One drug that might allow substantial short-
ening of therapy while maintaining high efficacy is rifapentine
(RPT), a rifamycin with a prolonged half-life. Zhang and col-
leagues (23) used a mouse model with BALBc and nude
(thymic-deficient) mice to evaluate the use of RPT instead of
RIF throughout therapy. Two months of daily INH, RPT, and
pyrazinamide followed by 1 month of daily RPT and INH
(2HPZ/1HP) was associated with rapid clearance of bacilli but
significant relapse rates in nude mice or in BALBc mice given
cortisone. However, there were no relapses after treatment with
2HPZ/4HP in either group of mice. The authors concluded that
therapy of 4 or 5 months might be sufficient, but this treatment
was not tested. Such mouse studies provide an indication of
efficacy and suggest which combination of drugs to pursue fur-
ther. Establishing efficacy of a candidate drug in clinical trials,
however, has proved to be a significant challenge. The measure
most commonly used to assess efficacy in phase 2 trials, the
sputum culture status on solid media at 2 months after therapy
initiation, has recently come under scrutiny. Nahid and col-
leagues provide a TB biomarker and surrogate endpoint research
roadmap that includes the development of a TB biorepository
that could support future biomarker discovery and validation
programs (24).
This same group found that treatment of the thymically de-
ficient mice with the standard regimen of 2HRZ/4HR resulted in
frequent emergence of INH monoresistant strains, which was
prevented by adding ethambutol (EMB), a point of interest
given the limited data on whether EMB helps to prevent resis-
tance. EMB was effective even though it was only given during
Pulmonary, Sleep, and Critical Care Updates
the initial 2 months of therapy, emphasizing that this is the crit-
ical period to prevent the emergence of resistance (i.e., when the
bacillary load is high).
Louw and colleagues (25) demonstrated that RIF-resistant
strains could be made susceptible to RIF by coadministration of
verapamil or reserpine. These compounds could overcome RIF
resistance by preventing efflux of RIF, which increased intra-
cellular RIF concentrations. These in vitro findings were con-
firmed in mice infected with RIF monoresistant strains that
responded to treatment with RIF and verapamil or with RIF
and reserpine but did not respond to treatment with any of
these three drugs alone. The duration of this effect is unknown,
but these findings suggest that novel approaches to therapy of
patients with limited options, such as the recently reported
patients with totally drug-resistant strains (26) in whom resto-
ration of RIF efficacy could have major benefits.
Shorter, safer, and more effective therapy for LTBI would
represent a major advance for TB control and could significantly
accelerate progress toward TB elimination. Zhang and col-
leagues (27) evaluated several short-course LTBI treatment
regimens in a mouse model of LTBI, in which mice received
aerosolized recombinant BCG vaccine and then a low-dose
aerosol of virulent M. tuberculosis 6 weeks later. Of the regi-
mens tested, INH alone for up to 6 months was least effective.
Results were similar with daily RIF alone for up to 4 months,
daily INH and RIF for 3 months, INH and RPT once weekly for
3 months, or daily TMC207 for up to 4 months. All regimens
achieved superior results compared with INH alone. Results
with daily RPT given alone were better than all these other
regimens, although the best regimen was the combination of
TMC207 and RPT daily, which resulted in complete clearance
of bacteria in the mouse lung within 1 month. The lowest re-
lapse rates were seen with RPT daily.
These results suggest that RPT alone or TMC207 plus RPT
given daily for 1 to 2 months may be adequate for LTBI ther-
apy. Given that the half-life of RPT is five times longer than
RIF, it is possible that daily RPT is successful because serum
concentrations are very high after the first few days. Pharma-
cokinetic studies will be useful to assess this. (One may specu-
late that higher dosing of RIF could achieve similar effects as
daily RPT.) Safety and tolerability studies of daily RPT in
humans are needed before large-scale human trials can begin
testing these very promising ultra-short LTBI regimens. Such
studies are under way.
TB is one of the most important infectious complications of
HIV and remains the leading cause of death among HIV-
infected persons. Luetkemeyer and colleagues (28) reviewed
the need for inclusion of HIV-infected individuals in all stages
of development of new drugs for treatment of active and latent
TB. In addition to the high morbidity and mortality associated
with TB in HIV-coinfected individuals, adverse events, drug
absorption, metabolism, and interactions may be very different
in these patients. The authors suggested that HIV-infected indi-
viduals should be included in pharmacokinetic studies to assess
absorption, metabolism, excretion, and drug interactions with
various anti-retroviral agents and should be included in phase
2 trials to assess the safety and tolerability of new drugs. One
important challenge is the difficulty of microbiologic confirmation
for initial diagnosis and end-point assessment of active TB. Phar-
maceutical companies may be unwilling to bear the substantial
costs for early-stage assessments of drugs that may never make it
to market. However, investments needed for these early-stage
evaluations could be potentially borne by other organizations,
such as the Global TB Alliance. Given the well documented
burden of TB among HIV-infected individuals and the recognized
problems of current TB therapy for this group of patients, it
1269
seems imperative to include coinfected patients in all phases of
drug development and in phase 1, 2, and 3 trials.
TREATMENT OF NONTUBERCULOUS MYCOBACTERIA
Mycobacterium abscessus complex is comprised of three closely
related species: M. abscessus (sensu stricto) (referred to as M.
abscessus), M. massiliense, and M. bolletii; however, little is
known regarding the clinical presentation and treatment re-
sponse of the different species within the complex. Using ar-
chived clinical isolates of M. abscessus complex, Koh and
colleagues (29) performed molecular identification of the spe-
cies and then compared clinical characteristics and outcomes of
treatment between 64 patients with M. abscessus lung disease
and 81 patients with M. massiliense lung disease. Whereas the
clinical and radiographic manifestations of disease were similar,
the proportion of patients with durable sputum conversion in
response to a clarithromycin-based regimen was higher in
patients with M. massiliense infection (88%) as compared with
M. abscessus infection (25%; P , 0.001). This difference is
likely explained by the fact that inducible resistance to clari-
thromycin was found in all tested M. abscessus isolates (n ¼
19) but in none of the M. massiliense isolates (n ¼ 28).
CONCLUSIONS
The past decade has seen an explosion of research in TB epide-
miology, diagnosis, and treatment that has not been seen since
the 1960s. The payoff from research is always slow, but the recent
downturn in global incidence, for the first time in 20 years, sug-
gests that payoff may be happening. The resurgence of TB in the
1980s is a reminder that M. tuberculosis is a worthy adversary,
ready to stage an impressive comeback if the attention of the
medical and scientific community turns elsewhere. Now that
progress is being made on the scientific and public health fronts,
it is not the time to turn away from TB but rather to continue
present efforts to find better diagnostic and treatment tools and
strategies to achieve a permanent reduction in global TB.
Author disclosures are available with the text of this article at www.atsjournals.org.
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