From: Subject: Primary Multidrug-Resistant Tuberculosis -- Ivanovo Oblast, Russia, 1999 Date: Mon, 30 Jun 2003 16:07:20 +0300 MIME-Version: 1.0 Content-Type: multipart/related; boundary="----=_NextPart_000_0070_01C33F21.AF568720"; type="text/html" X-MimeOLE: Produced By Microsoft MimeOLE V6.00.2800.1106 This is a multi-part message in MIME format. ------=_NextPart_000_0070_01C33F21.AF568720 Content-Type: text/html; charset="Windows-1252" Content-Transfer-Encoding: quoted-printable Content-Location: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm4830a3.htm Primary Multidrug-Resistant Tuberculosis -- Ivanovo = Oblast, Russia, 1999
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Primary Multidrug-Resistant Tuberculosis -- Ivanovo Oblast, = Russia,=20 1999

The incidence of tuberculosis (TB) in the Russian Federation = has=20 increased steadily from 34 per 100,000 population in 1991 to 78 = per=20 100,000 in 1998 (Central Tuberculosis Research Institute, = unpublished=20 data, 1999). To reverse this trend, in 1995, federal and local=20 governments, with assistance from the World Health Organization = (WHO),=20 implemented a pilot project using the WHO TB-control strategy of = directly=20 observed therapy, short-course (DOTS)* in Ivanovo oblast (1998 = population:=20 approximately 1.3 million), a district 165 miles (280 km) = northeast of=20 Moscow. This report documents a substantial increase in primary=20 multidrug-resistant TB (P-MDRTB) in the civilian population of = Ivanovo=20 from January 1996 through October 1998 and a high prevalence of=20 alcoholism, previous incarceration, unemployment, and history of=20 homelessness among persons infected with both drug-susceptible and = drug-resistant Mycobacterium tuberculosis strains.

Despite implementation of DOTS in Ivanovo in October 1995, as = of=20 October 1998, approximately 30% of 514 never-treated (defined as = less than=20 1 month of previous treatment), smear-positive TB patients had = poor=20 treatment outcomes (i.e., relapse, treatment failure, or death). = P-MDRTB,=20 defined as M. tuberculosis isolates resistant to at least = isoniazid=20 and rifampin in never-treated TB patients, was suspected to be a = major=20 contributing factor to these poor outcomes. WHO requested CDC's = assistance=20 to investigate trends in P-MDRTB, identify epidemiologic risk = factors for=20 P-MDRTB, and examine outcomes for persons with P-MDRTB.

The Ivanovo TB laboratory performed drug-susceptibility testing = on all=20 514 M. tuberculosis isolates; 26 (5%) had primary multidrug = resistance. The percentage of P-MDRTB cases more than doubled = after=20 program implementation, from 3.8% (seven of 186) in 1996 to 9.4% = (11 of=20 117) during the first 9 months of 1998 (chi-square for linear = trend; p=20 less than 0.05).

To identify risk factors for P-MDRTB, a case-control study was=20 conducted in February 1999 of never-treated, smear- and = culture-positive=20 pulmonary TB patients reported during October 1995-October 1998. A = case of=20 P-MDRTB was defined as culture-confirmed MDRTB in a patient; = controls were=20 patients with culture-confirmed drug-susceptible TB. Controls were = frequency-matched to cases by quarter-year of report; three = controls per=20 case were chosen randomly. Risk factor data, drug susceptibility = results,=20 and clinical outcomes were obtained from the WHO project database, = a=20 detailed local TB database, and medical chart reviews.

Twenty-six P-MDRTB case-patients and 76 frequency-matched = controls were=20 enrolled in the study. The mean ages of both case-patients and = controls=20 were similar (44 years versus 46 years; range: 15-76 years); 92% = of=20 case-patients and 84% of controls were male. None of the = case-patients or=20 controls were infected with human immunodeficiency virus. = Case-patients=20 were more likely than controls to have been hospitalized = previously (46%=20 versus 25%; odds ratio [OR]=3D1.9; 95% confidence interval = [CI]=3D0.8-4.3),=20 incarcerated previously (44% versus 29%; OR=3D1.6; 95% = CI=3D0.7-3.6),=20 unemployed at time of diagnosis (58% versus 55%; OR=3D1.3; 95% = CI=3D0.6-3.0),=20 or to have a history of alcoholism (65% versus 61%; OR=3D1.3; 95%=20 CI=3D0.6-2.9), but the differences were not statistically = significant.=20 However, compared with controls, case-patients were significantly = more=20 likely to have a history of homelessness (23% versus 5%; OR=3D3.1; = 95%=20 CI=3D1.1-8.8; p=3D0.04).

During October 1995-October 1998, 5% (one of 19) of = case-patients=20 compared with 77% (43 of 56) of controls were cured (i.e., = negative sputum=20 smear at treatment completion and on at least one previous = occasion [3])=20 by the standardized 6-month DOTS treatment regimen (p less than = 0.001).=20 Furthermore, 27% (six of 22) of case-patients, compared with 8% = (six of=20 75) of controls, died of TB (hazard ratio for death associated = with TB=20 among case-patients=3D2.2; p=3D0.17, Cox proportional hazard = analysis).

Reported by: I Danilova, M Stoyunin, E Repina, M Vorobiov, O = Adreevna,=20 Ivanovo Oblast TB Dispensary, Ivanovo; A Khomenko, V Puzanov, L = Kapkov, V=20 Punga, Central TB Research Institute, Moscow; G Oswald, N = Afanasiev, C=20 Carrino, United States Agency for International Development, = Moscow,=20 Russia. GB Migliori, M Ambrosetti, World Health Organization, = Geneva,=20 Switzerland; FS Maugeri, Tradate, Italy. M Grzemska, M Espinal, M=20 Raviglione, World Health Organization, Geneva, Switzerland. A = Goldfarb,=20 Public Health Research Institute, New York City. A Slutsky, = Massachusetts=20 State Laboratory, Boston, Massachusetts. International Activity = and Field=20 Services Br, Div of TB Elimination, National Center for HIV, STD, = and TB=20 Prevention, CDC.

Editorial Note:

Worldwide, approximately 8 million TB cases and 2 million TB = deaths=20 occur annually (4). MDRTB is present on five continents and is = increasing=20 (5). The four-drug regimen used as part of the WHO DOTS strategy = results=20 in high cure rates in areas with low levels of resistance. = However, in=20 communities such as Ivanovo that have high levels of drug = resistance,=20 additional strategies are needed for patients with drug-resistant = TB,=20 including rapid assessment of drug susceptibilities and use of=20 alternative, "second-line" TB drugs (5,6).

In the Russian Federation, the incidence of all TB and of=20 drug-resistant TB is increasing in the civilian and the prison = populations=20 (7,8). The findings in this report identify a significant increase = in=20 P-MDRTB in the civilian population of Ivanovo from January 1996 = through=20 October 1998 and a high prevalence of alcoholism, previous = incarceration,=20 unemployment, and history of homelessness among persons infected = with=20 drug-resistant and drug-susceptible M. tuberculosis = strains. Drug=20 resistance contributed to 17% of the poor treatment outcomes = observed in=20 Ivanovo; however, most of these poor outcomes probably were = associated=20 with delayed diagnosis, treatment interruption, failure to ensure = patient=20 adherence, and other program-related factors (5). Analysis of the = impact=20 of these factors on treatment outcome among the patients in = Ivanovo is=20 under way.

The findings in this report are subject to at least three = limitations.=20 First, details about previous prison and hospitalization history = were not=20 available for all study participants. This limited the ability to = identify=20 specific high-risk exposures in the community. Second, the = relatively=20 small sample size limited the power to detect statistically = significant=20 differences between cases and controls. Third, case-patients and = controls=20 described in this report are limited to Ivanovo and may not be=20 representative of TB patients in other geographic regions within=20 Russia.

On the basis of these findings, CDC made two recommendations to = improve=20 the outcomes of TB-control activities in Ivanovo. First, to = prevent=20 further spread of drug-resistant and drug-susceptible TB, = TB-control=20 efforts must target high-risk populations for active case finding = and=20 assurance of completion of therapy. Second, rapid = drug-susceptibility=20 testing and the use of appropriate second-line TB drug regimens = for=20 patients with demonstrated MDRTB should be implemented to improve=20 treatment outcomes in active TB patients and to reduce the = widespread=20 emergence of MDRTB in this community. Until second-line drug=20 susceptibility testing is widely available, one or more = second-line=20 treatment regimens will need to be used empirically (based on = knowledge of=20 drug-resistance profiles in the community) for these patients. = Expansion=20 of rapid drug susceptibility testing and a reliable drug supply = will=20 facilitate the design of more individualized treatment regimens in = patients with drug-resistant TB, improve the likelihood of cure, = prevent=20 the transmission of drug-resistant TB, and avert premature deaths=20 attributable to MDRTB.

References

  1. China Tuberculosis Control Collaboration. Results of = directly=20 observed short-course chemotherapy in 112,842 Chinese patients = with=20 smear-positive tuberculosis. Lancet 1996;347:358-62.=20
  2. Kumaresan JA, Ahsan Ali AK, Parkkali LM. Tuberculosis = control in=20 Bangladesh: success of the DOTS strategy. Int J Tuberc Lung Dis=20 1998;2:992-8.=20
  3. World Health Organization. Global tuberculosis control: WHO = report=20 1999. Geneva, Switzerland: World Health Organization, 1999; = report no.=20 WHO/CDS/CPC/TB/99.259.=20
  4. World Health Organization. World health report 1999: making = a=20 difference. Geneva, Switzerland: World Health Organization, = 1999.=20
  5. World Health Organization. Anti-tuberculosis drug resistance = in the=20 world: the WHO/IUATLD global project on anti-tuberculosis drug=20 resistance surveillance, 1994-1997. Geneva, Switzerland: WHO = Global=20 Tuberculosis Program, 1997; report no. WHO/TB/97.229.=20
  6. Crofton J, Chaulet P, Maher D. Guidelines for the management = of=20 drug-resistant tuberculosis. Geneva, Switzerland: World Health=20 Organization, 1997; report no. WHO/TB/96.210 (rev. 1).=20
  7. Coninx R, Mathieu C, Debacker M, et al. First-line = tuberculosis=20 therapy and drug-resistant Mycobacterium tuberculosis in = prisons.=20 Lancet 1999;353:969-73.=20
  8. Kimerling ME, Kluge H, Vezhina N, et al. Inadequacy of the = current=20 WHO re-treatment in a central Siberian prison: treatment failure = and=20 MDR-TB. Int J Tuberc Lung Dis 1999;3:451-3.

* DOTS consists of 1) government commitment to sustained TB = control; 2)=20 a bacteriologically confirmed diagnosis; 3) a standardized = short-course=20 multidrug regimen for treatment of active TB, provided under = direct=20 observation; 4) a regular, uninterrupted supply of drugs and = diagnostic=20 materials; and 5) the systematic monitoring and evaluation of = program=20 activities. In other countries, DOTS programs have resulted in = successful=20 completion of therapy for greater than or equal to 80% of patients = (1-3).

Disclaimer=20   All MMWR HTML versions of articles are = electronic=20 conversions from ASCII text into HTML. This conversion may have = resulted=20 in character translation or format errors in the HTML version. = Users=20 should not rely on this HTML document, but are referred to the = electronic=20 PDF version and/or the original MMWR paper copy for the = official=20 text, figures, and tables. An original paper copy of this issue = can be=20 obtained from the Superintendent of Documents, U.S. Government = Printing=20 Office (GPO), Washington, DC 20402-9371; telephone: (202) = 512-1800.=20 Contact GPO for current prices.

**Questions or messages = regarding errors in formatting should be addressed to mmwrq@cdc.gov.=20

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