|
|
Letter
Drug-Resistant Mycobacterium
tuberculosis among New Tuberculosis Patients, Yangon, Myanmar
Sabai Phyu,* Ti Ti,† Roland Jureen,* Thandar Hmun,† Hlaing Myint,†
Aye Htun,† Harleen M.S. Grewal,* and Bjarne Bjorvatn*
*University of Bergen, Bergen, Norway; and †National TB Programme, Yangon,
Myanmar
Suggested citation for this article: Phyu S,
Ti T, Jureen R, Hmun T, Myint H, Htun A, Grewal HMS, et al. Drug-resistant
Mycobacterium tuberculosis among new tuberculossi patients, Yangon,
Myanmar. Emerg Infect Dis [serial online] 2003 Feb [date cited].
Available from: URL: http://www.cdc.gov/ncidod/EID/vol9no2/02-02-0128.htm
To the Editor: Spread of drug-resistant tuberculosis (TB) and
disastrous rates of HIV-TB co-infection pose serious threats to TB-control
programs around the world (1). The World Health Organization/International
Union Against Tuberculosis and Lung Diseases urges all national TB programs
to practice the Directly Observed Treatment-Short Course (DOTS) strategy
as well as to closely monitor the patterns and trends of anti-TB drug
resistance (2). Such data allow an assessment of the
quality of TB control, help forecast future trends of drug-resistance,
and serve as guidelines for suitable therapy.
In 1997 the national TB programs of Myanmar introduced DOTS in the capital
city, Yangon, which has approximately 5 million inhabitants. All new case-patients
in national TB program clinics are routinely treated with isoniazid, rifampicin,
ethambutol, and pyrazinamide without drug susceptibility testing of Mycobacterium
tuberculosis. However, isolates from previously treated patients are
frequently tested for drug susceptibility, and treatment is guided by
the results. Myanmar is one of the 22 countries that account for 80% of
the world’s new TB cases (3), yet little is known about
drug-resistant TB in that country. We report on the pattern of drug resistance
to first-line anti-TB drugs among M. tuberculosis complex isolates
from Zone 1 TB center in Yangon, which receives approximately 70% of the
national TB programs’ TB cases in Yangon. Of the 864 patients who attended
this center in July 2000, a total of 202 were diagnosed as having pulmonary
TB on the basis of medical history, clinical signs, two smear-positive
sputum samples, and chest x-ray, if necessary. Approximately half of these
cases were new pulmonary TB patients, i.e. smear-positive patients who
had never been treated previously. Sputum specimens from 72 consecutive,
new pulmonary TB case-patients were injected on Ogawa medium according
to standard procedure (2); samples from 68 patients (94%)
were culture-positive. Isolates from 17 patients were lost for further
study because of bacterial contamination and failure to grow on subculture.
Thus, isolates from 51 patients were available for the current investigation.
By using the AccuProbe Mycobacterium tuberculosis complex test
(Gen-Probe, San Diego, CA), all isolates were found to belong to the M.
tuberculosis complex. Testing of isolates for susceptibility to isoniazid,
rifampicin, ethambutol, and streptomycin was performed by using the standard
Mycobacteria Growth Indicator Tube manual system, as recommended by the
manufacturer (Becton Dickinson, Sparks, MD). The Wayne assay (4),
which measures the activity of pyrazinamidase, was used for pyrazinamide
susceptibility testing. This assay was performed according to World Health
Organization guidelines for speciation within the M. tuberculosis complex
(5). Eighteen isolates (35%) were resistant to any one
of the five anti-TB drugs. Thirteen isolates (26%) were resistant to isoniazid,
nine isolates (18%) to streptomycin, four isolates (8%) to ethambutol,
one isolate (2%) to rifampicin, and one isolate (2%) to pyrazinamide.
Only one isolate (2.0%) was multidrug resistant (MDR)-M. tuberculosis,
i.e., resistant to both isoniazid and rifampicin.
The World Health Organization/International Union Against Tuberculosis
and Lung Diseases global survey in the year 2000 (6)
showed that the prevalence of resistance to at least one anti-TB drug
(isoniazid, rifampicin, ethambutol, and streptomycin) among new cases
ranged from 1.7% to 36.9%. In our study, 33.3% of the isolates from new
pulmonary TB patients were resistant to at least one of these drugs. The
finding shows that a relatively high frequency of drug resistance exists
among our patients. If pyrazinamide is included in the calculation, the
proportion of drug resistance among our patients is 35.3%. In 1994, Ti
et al. reported that MDR-TB represented 1.25% of the isolates from 400
patients with newly diagnosed pulmonary TB who attended the Zone 1 TB
center (7). When one considers the corresponding figure
of 2.0% in the current material, frequency of MDR-TB in Yangon does not
seem to have changed dramatically during the period 1994–2000. MDR-TB
among new patients appears to be less common in Yangon than in big cities
in Thailand (4.2%) (8) and in China (4.5%) (6).
However, a substantial number of our isolates (15.7%) were resistant to
two or more anti-TB drugs, in most cases to both isoniazid and streptomycin
(9.8%). In the 1994 report by Ti et al., mono-resistance to streptomycin
(6.5%) or isoniazid (5.8%) predominated, and 2.0% of the isolates were
resistant to both isoniazid and streptomycin (7). Our
present results, therefore, indicate that drug resistance is an imminent
threat to TB-control efforts in Yangon, although MDR-TB still seems to
be relatively rare.
The low number of MDR cases in our study could partly be explained by
demographic features of the studied population, which is composed predominately
of people residing in satellite townships of Yangon. These townships usually
attract young people who immigrate to Yangon from village areas. These
immigrants are less likely to have previous exposure to TB than the permanent
population since the prevalence of TB infection is lower in rural than
in urban areas (9). Moreover, population densities of
the satellite townships are 2- to 10-fold lower than in inner Yangon city
(Myanmar Central Statistical Organization). The high number of drug-resistance
cases among our patients with newly detected TB could be explained by
an undisclosed past exposure to anti-TB drugs. The case detection rate
reported by the Myanmar national TB programs is 48% (3),
suggesting that many TB patients receive their treatment elsewhere. A
World Health Organization report (10) indicates that
>80% of the health-care expenditure in Myanmar and other Asian countries
such as India, Vietnam, and Cambodia is spent in the private sector. In
such countries, poor treatment practices in the private sector may lessen
the impact of the DOTS implemented by national TB programs and contribute
to a growing incidence of drug-resistant TB. This problem will undoubtedly
be escalated by the availability of anti-TB drugs without prescription.
HIV-TB co-infection often results in increased frequency of adverse drug
effects, which may reduce compliance and increase induction of drug resistance.
Although the prevalence of HIV positivity among our patients is unknown,
a preliminary study from Yangon shows that the prevalence of drug-resistant
TB among HIV-seropositive and -seronegative patients is the same (pers.
comm., Myanmar national TB
programmes]. To our knowledge, this report is the first to describe drug-resistant
patterns in M. tuberculosis isolates from Myanmar.
Acknowledgments
We thank Dr. Elling Ulvestad for providing excellent
laboratory facilities and Grete Hopland and Synnøve Simonnes
for technical assistance.
This study was supported by the University of Bergen
and Haukeland University Hospital, Bergen, Norway.
References
- World Health Organization/Stop TB partnership. Stop
TB annual report 2001. Geneva: The Organization; 2001.
- De Kantor IN, Kim SJ, Frieden T, Laszlo A, Luelmo F, Norval P-Y, et
al. Laboratory services in tuberculosis control. Geneva: World Health
Organization; 1998.
- World Health Organization. Global tuberculosis control: surveillance,
planning, financing. Communicable diseases. Geneva: The Organization;
2002.
- Wayne LG. Simple pyrazinamidase and urease test for routine identification
of mycobacteria. Am Rev Respir Lung Dis 1974;109:147–51.
- Grange JM, Yates M, de Kantor IN. Guidelines for speciation within
the Mycobacterium tuberculosis complex. 2nd ed. Geneva: World
Health Organization; 1996.
- The World Health Organization/International Union Against Tuberculosis
and Lung Diseases global project on anti-tuberculosis drug resistance
surveillance. Anti-tuberculosis drug resistance in the world–report
no. 2, prevalence and trends. Geneva: The Organization; 2000.
- Ti T, Aye T, Mu SH, Myint KM, Min A, Maung T, et al. A random sample
study of initial drug resistance among tuberculosis cases in Yangon,
Myanmar. Proceedings of the Myanmar Health Research Congress. 1995 Dec;
Yangon, Myanmar. Yangon, Myanmar: Department of Medical Research, Ministry
of Health; 1995.
- Riantawan P, Punnotok J, Chaisuksuwan R, Pransujarit V. Resistance
of Mycobacterium tuberculosis to antituberculosis drugs in the
central region of Thailand, 1996. Int J Tuberc Lung Dis 1998;2:616–20.
- Roelsgaard E, Iversen E, Bløcher C. Tuberculosis in tropical Africa.
An epidemiological study. Bull World Health Organ 1964;30:459–518.
- Health System: Improving performance. The world health report 2000.
Geneva: World Health Organization; 2000.
|
