Targeted Drug-Resistance Testing Strategy for MDR TB | CDC EID

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Volume 17, Number 3–March 2011
Research
Targeted Drug-Resistance Testing Strategy for Multidrug-Resistant Tuberculosis Detection, Lima, Peru, 2005–2008
Gustavo E. Velásquez, Martin Yagui, J. Peter Cegielski, Luis Asencios, Jaime Bayona, Cesar Bonilla, Hector O. Jave, Gloria Yale, Carmen Suárez, Sidney Atwood, Carmen C. Contreras, and Sonya S. Shin
Author affiliations: Brigham and Women's Hospital, Boston, Massachusetts, USA (G.E. Velásquez, S. Atwood, S.S. Shin); Instituto Nacional de Salud, Lima, Peru (M. Yagui, L. Asencios); Centers for Disease Control and Prevention, Atlanta, Georgia, USA (J.P. Cegielski); Socios En Salud, Lima (J. Bayona, C.C. Conteras, S.S. Shin); Partners In Health, Boston (S.S. Shin); Dartmouth College, Hanover, New Hampshire, USA (J. Bayona); Ministerio de Salud del Perú, Lima (C. Bonilla, H.O. Jave); Dirección de Salud V Lima Ciudad, Lima (G. Yale); and Dirección de Salud IV Lima Este, Lima (C. Suárez)

Suggested citation for this article

Abstract
The Peruvian National Tuberculosis Control Program issued guidelines in 2006 specifying criteria for culture and drug-susceptibility testing (DST), including district-level rapid DST. All patients referred for culture and DST in 2 districts of Lima, Peru, during January 2005–November 2008 were monitored prospectively. Of 1,846 patients, 1,241 (67.2%) had complete DST results for isoniazid and rifampin; 419 (33.8%) patients had multidrug-resistant (MDR) TB at the time of referral. Among patients with new smear-positive TB, household contact and suspected category I failure were associated with MDR TB, compared with concurrent regional surveillance data. Among previously treated patients with smear-positive TB, adult household contact, suspected category II failure, early relapse after category I, and multiple previous TB treatments were associated with MDR TB, compared with concurrent regional surveillance data. The proportion of MDR TB detected by using guidelines was higher than that detected by a concurrent national drug-resistance survey, indicating that the strategy effectively identified patients for DST.

Multidrug-resistant tuberculosis (MDR TB) is defined as infection with Mycobacterium tuberculosis with in vitro resistance to at least isoniazid and rifampin. The incidence of MDR TB disease was estimated to be 0.5 million in 2007, with a prevalence of as many as 2 million cases worldwide (1). Although no single best approach to MDR TB treatment has been recognized, rapid drug-susceptibility testing (DST) and prompt initiation of effective treatment are achievable goals. Ideally, treatment is based on timely, accurate DST, but if universal DST is not possible or not yet available, the national TB control program can prioritize patients at increased risk for MDR TB.

Rapid DST methods should minimize delays to initiation of appropriate treatment (2,3). Numerous assays have been developed that have characteristics suitable for use in low-income settings, including low cost, modest technical demand, and high accuracy (4–6). The nitrate reductase assay (NRA), also known as the Griess method, has demonstrated acceptable sensitivity, specificity, and speed compared with conventional DST and rapid phenotypic DST methods (7,8). This phenotypic assay was developed in Russia as a low-cost drug-susceptibility test that can be used in areas of moderate technical capacity (9). The method is based on a nitrate-reductase colorimetric reaction that uses Lowenstein-Jensen (LJ) medium prepared with antimicrobial drugs (9). Although initially validated as an indirect method, it was implemented as a direct method by the Peruvian National Institute of Health (INS) (10). The NRA yields drug-susceptibility information to isoniazid and rifampin 21–28 days after inoculating a smear-positive sputum sample (direct method) (10) or 8–10 days after obtaining a positive culture (indirect method). The pooled sensitivity and specificity of the NRA (on culture isolates and sputum) have been reported to be 97% and 100% for rifampin and 96% and 99% for isoniazid (11). The pooled sensitivity and specificity of direct NRA have been reported to be 99% and 100% for rifampin and 94% and 100% for isoniazid (12). A recent comparison of 4 rapid DST methods with conventional DST in the context of a clinical trial suggested they may be cost-effective when compared with other health interventions (13). On the basis in part of these data, the World Health Organization (WHO) recently endorsed the use of NRA for screening patients at risk of MDR TB (14).

Despite the development of promising commercial and noncommercial rapid methods for MDR TB diagnosis, how to implement those methods under program conditions remains largely unaddressed. DST performance in validation studies differs greatly from performance integrated within a TB control program. Furthermore, the performance of any method under program conditions depends not only on assay characteristics, but also on the assets of the laboratory network and National Tuberculosis Control Program (NTP) guidelines which define criteria for performing DST.

To address this gap, we evaluated the effects of a programmatic strategy for rapid screening for MDR TB among risk groups specified by the Peruvian NTP in April 2006 (15). At that same time, decentralized, district-level MDR TB screening was pilot tested in 2 district laboratories in Lima, Peru. In collaboration with the Peruvian NTP and the Peruvian National Reference Laboratory (NRL), we evaluated the effectiveness of these combined strategies for detecting MDR TB. We report the proportion of drug resistance among risk groups based on screening high-risk patients as defined by explicit criteria, including rapid methods of DST in one of the first countries to implement this strategy.

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Targeted Drug-Resistance Testing Strategy for MDR TB | CDC EID


Suggested Citation for this Article
Velásquez GE, Yagui M, Cegielski JP, Asencios L, Bayona J, Bonilla C, et al. Targeted drug-resistance strategy for multidrug-resistant tuberculosis detection, Lima, Peru. Emerg Infect Dis [serial on the Internet]. 2011 Mar [date cited].
http://www.cdc.gov/EID/content/17/3/432.htm

DOI: 10.3201/eid1703.101553


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Sonya S. Shin, Division of Global Health Equity, Brigham and Women's Hospital, FXB Bldg, 7th Floor, 651 Huntington Ave, Boston, MA 02115, USA; email: sshin@partners.org