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Acquired Multidrug-Resistant Tuberculosis --
Buenaventura, Colombia, 1998
In 1996, the incidence of tuberculosis (TB) in Colombia was
26.5 per
100,000 population, and mortality was 3.4 per 100,000; in
comparison, the
incidence in Buenaventura, a port town on the Pacific coast, was
90.5 per
100,000, and mortality was 9.4 per 100,000 (1). The prevalence of
multidrug-resistant tuberculosis (MDR-TB) (i.e., Mycobacterium
tuberculosis
isolates resistant to at least isoniazid {INH} and rifampin {RIF})
was not
known because susceptibility testing is not performed routinely,
and data
on drug resistance for the country have not been collected
systematically.
During October-November 1997, at the request of the Secretary of
Health in
Cali, Colombia, the International Center for Training and Medical
Investigation in Cali performed sputum cultures for M. tuberculosis
and
drug-susceptibility testing on isolates from 18 (75%) of 24 TB
patients in
Buenaventura who were known to be clinically unresponsive to
standard TB
treatment. MDR-TB was identified in 12 (67%) of these patients,
four of
whom subsequently died. In March 1998, the International Center for
Training and Medical Investigation and the Secretary of Health of
Colombia
invited CDC to participate in an investigation of these patients
with
MDR-TB. This report summarizes the findings of this investigation,
which
indicated that inconsistencies in treatment may have contributed to
this
outbreak, and provides recommendations for the prevention and
control of
MDR-TB in Buenaventura.
A case was defined as laboratory-confirmed MDR-TB in any of
the 24
clinically unresponsive TB patients. The median age of the 12
MDR-TB
case-patients was 30 years (range: 18-79 years); nine (75%) were
men, and
all were long-term residents of Buenaventura (median: 29 years;
range:
17-80 years). Of the 12, 10 (83%) had no known epidemiologic link
to
another MDR-TB case. Of seven persons who were tested for human
immunodeficiency virus infection, none were positive. Sputum
specimens from
five case-patients were smear-positive for acid-fast bacilli (AFB).
Clinical charts of all persons with MDR-TB were reviewed for
possible
factors associated with the development of MDR-TB. All
case-patients had
received a median of 3.5 years of TB treatment (range: 2-13 years);
however, 11 (92%) had treatment interrupted and reinitiated several
times.
Of the 12 case-patients, 10 had a history of not taking the
prescribed
anti-TB medications for at least 1 month. One patient had been
started on a
suboptimal initial treatment regimen instead of the recommended
regimen of
4 months of treatment with INH, RIF, pyrazinamide, and
streptomycin,
followed by 2 months of INH and RIF. Nine patients rema-ning
AFB-smear-positive after 4 months had not received the recommended
retreatment regimen. Eleven (92%) patients had TB medications
improperly
added and subtracted to their treatment regimen. Seven (58%)
patients had a
single drug added to a failing regimen. In addition, three of 10
case-patients with available data did not have sputum specimens
obtained
after failing to appear for treatment during at least 1 month, and
six of
nine case-patients with available data did not receive directly
observed
therapy (DOT). All 12 case-patients experienced at least two
instances of
incorrect treatment or management of their illness (median: 3.9;
range:
two-six) based on World Health Organization (WHO) and Colombian
treatment
protocols.
Reported by: LE Osorio, MV Villegas, AM Benitez, H Hernandez, JF
Miranda, N
Saravia, International Center for Training and Medical
Investigation, Cali;
MC Castano, N Henriquez, S Quinonez, Secretary of Health of the
Valle del
Cauca; LE Sanchez, Buenaventura Hospital, Cali, Colombia.
TB/Mycobacteriology Br, Div of AIDS, STD, and TB Laboratory
Research,
National Center for Infectious Diseases; International Activity,
Field Svcs
Br, Div of Tuberculosis Elimination, National Center for HIV, STD,
and TB
Prevention; and an EIS Officer, CDC. Editorial Note
Editorial Note: Each year, approximately 8 million new cases and 3
million
deaths worldwide are attributable to TB (2). Most patients
diagnosed with
TB harbor drug-susceptible strains of M. tuberculosis that respond
well to
a short-course (6-8 months) multidrug chemotherapy regimen
recommended by
WHO (3). Although the cure rate is greater than 80% in most
countries where
the regimen has been successfully applied and its administration
appropriately supervised (3), the worldwide emergence of MDR-TB
threatens
global TB-control efforts (4).
Treatment history is the most significant factor associated
with the
appearance of drug-resistant TB (5). This report identified
specific
aspects of treatment and patient management that contributed to
acquired
drug resistance in Buenaventura. The most common factors in this
study were
failure to start the WHO-recommended retreatment regimen in
patients who
were unresponsive to the initial regimen and inappropriate
additions or
subtractions of medications during treatment. M. tuberculosis
organisms
also may have acquired drug resistance as a result of patient
factors
(e.g., nonadherence with treatment) and programmatic factors (e.g.,
lack of
DOT) (4). Many patients had treatment interrupted and reinitiated
in part
because, in 1996, the TB-control program was decentralized from a
hospital-based system to a health-post-based system.
The findings in this report are subject to at least three
limitations.
First, details of the initial TB diagnosis and treatment episode
were not
available for all patients. Second, clinical records and specimens
were not
available to ascertain whether a patient was originally infected
with a
drug-resistant strain or the strain acquired the drug resistance
during
therapy. Third, MDR-TB case-patients described in this report may
not be
representative of all MDR-TB patients in Buenaventura.
The findings from this investigation have led to improvements
in
TB-control efforts in Buenaventura in the context of a
decentralized health
system. Structural changes in the overall TB program have been
implemented,
including the designation of personnel to direct the program and
the
installation of mechanisms to monitor and evaluate TB services.
Training
for physicians and health-care workers in the management of TB and
MDR-TB
has been initiated. To improve patient adherence to TB treatment,
the use
of WHO-recommended DOT was initiated for both MDR-TB patients and
other TB
patients. Finally, new treatment regimens have been designed for
each
patient, based on drug-susceptibility testing performed by the
International Center for Training and Medical Investigation.
References
Ministry of Health, Republic of Colombia. Guide to integrated
care:
prevention and control of tuberculosis {Spanish}. Bogota,
Colombia:
Ministry of Health, 1997.
Dolin PJ, Raviglione MC, Kochi A. Global tuberculosis incidence
and
mortality during 1990-2000. Bull World Health Organ
1994;72:213-20.
World Health Organization. Treatment of tuberculosis:
guidelines for
national programmes. 2nd ed. Geneva, Switzerland: World Health
Organization, 1997; report no. WHO/TB/97.220.
Pablo-Mendez A, Raviglione MC, Laszlo A, et al. Global
surveillance for
antituberculosis-drug resistance, 1994-1997. N Engl J Med
1998;338:
1641-9.
World Health Organization. Anti-tuberculosis drug resistance in
the
world: the WHO/IUTALD Global Project on Anti-tuberculosis Drug
Resistance Surveillance, 1994-1997. Geneva, Switzerland: WHO
Global
Tuberculosis Programme, 1997; report no. WHO/TB/97.229.
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