Patients taking directly observed therapy (DOTS) for
tuberculosis (TB) may be potentially infectious for longer than previously
thought, investigators report in the August 15th edition of Clinical Infectious Diseases. Moreover,
the researchers found that many patients were TB culture-positive despite being
Although prolonged smear and/or culture positivity during treatment
was associated with the presence of drug-resistant TB, the majority of patients with drug-sensitive TB also took longer than two weeks to test culture-negative, and 10% of patients with drug-sensitive TB were still culture-positive at least 2 months after starting treatment.
It has long been thought that patients with drug-susceptible TB
are non-infectious after two weeks of therapy for the infection.
“The data presented here question the notion that patients
with TB who are culture positive at baseline are non-infectious after 2 weeks
of treatment or a negative smear”, write the investigators, “most patients are
both smear and culture positive at 2 weeks, and significant proportions remain
positive for months.”
The study was conducted in Lima, Peru, and involved 93
patients with both culture and smear-positive TB who were provided with DOTS.
In the six months following the initiation of TB therapy the
patients provided sputum samples. These were analysed to see if sputum which were
smear-negative were also culture-negative; how long it took for TB to become
both smear and culture-negative; and to see if the presence of drug resistance
was associated with delays in becoming non-infectious.
Patients became smear-negative a median of 18 days after
starting TB therapy, and culture-negative after a median of 41 days.
However, it took a median of 48 days for 90% of patients to become smear-negative, and median of 93 days for 90% to attain culture-negativity.
The presence of multidrug-resistant tuberculosis (MDR-TB) was associated
with a longer time to both smear and culture negativity.
Ninety percent of patients with drug-sensitive TB were culture
negative after 60 days, but it took a median of 124 days for patients with
MDR-TB to achieve this outcome.
In statistical analysis, MDR-TB was shown to be a
significant predictor of delayed time to attaining negative cultures (p =
At treatment initiation, 67% of patients with
culture-positive MDR-TB were also smear positive. After 120 days of treatment,
80% of patients with culture-positive samples were MDR-TB smear-negative.
Among patients with drug-sensitive TB, the median time to culture-negativity was 36.5 days
“This study demonstrates that patients with TB who have
fully susceptible disease remain sputum culture positive for much longer than
is conventionally believed”, comment the investigators.
They add, “conversion from smear or culture positivity to
negativity is significantly delayed by both MDR and resistance that is not
Under most DOTS treatment regimens, patients “step-down”
from therapy consisting of four drugs to a combination of two drugs after 60
days if smear-negative. The investigators comment, “our data indicate frequent persistent culture
positivity among smear-negative patients at this time point; this may partly
explain high rates of apparent recurrence of MDR among patients considered
‘cured’ by smear diagnosis.”
The researchers conclude, “long-term smear-negative shedding
and drug resistance must be considered jointly if TB transmission is to be
The author of an accompanying editorial suggests that the
study illustrates “the need for new research efforts to evaluate and challenge
our old TB control paradigms. During the past 10 years, TB has changed the
rules of the game, whereas our policies have stayed the same wishful thinking.
New public health policies based on scientific evidence are urgently needed to
combat the growing scourge of drug-resistant TB.”