Evaluation of Xpert MTB/RIF and MODS assay for the diagnosis of pediatric tuberculosis

BMC Infectious Diseases

Maxine Caws¹  Jeremy Farrar¹  Marcel Wolbers¹  Nguyen Huy Dung²  Do Chau Giang²  Vo Thi Ha²  Nguyen Thi Bich Tuyen²  Tran Van Quyet²  Nguyen Thi Ngoc Lan²  Nguyen Dang Quang²  Tran Ngoc Duong²  Do Dang Anh Thu³  Nguyen Duc Anh³  Dang Thi Minh Ha²  Nguyen Thi Quynh Nhu³ 

[1] Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, Old Road, Headington, Oxford, UK;Pham Ngoc Thach Hospital for Tuberculosis and Lung Diseases, 120 Hung Vuong, District 5, Ho Chi Minh City, Vietnam;Oxford University Clinical Research Unit, Hospital for Tropical Diseases, 764 Vo Van Kiet, District 5, Ho Chi Minh City, Vietnam

关键词: Childhood;    Pediatric;    MODS;    GeneXpert MTB/RIF;    Tuberculosis;   

Others  :  1158541
DOI  :  10.1186/1471-2334-13-31

 received in 2012-08-02, accepted in 2013-01-21,  发布年份 2013

【 摘 要 】

Background

Tuberculosis (TB) in children is rarely confirmed due to the lack of effective diagnostic tools; only 10 to 15% of pediatric TB is smear positive due to paucibacillary samples and the difficulty of obtaining high-quality specimens from children. We evaluate here the accuracy of Xpert MTB/RIF in comparison with the Micoroscopic observation drug susceptibility (MODS) assay for diagnosis of TB in children using samples stored during a previously reported evaluation of the MODS assay.

Methods

Ninety-six eligible children presenting with suspected TB were recruited consecutively at Pham Ngoc Thach Hospital in Ho Chi Minh City Viet Nam between May to December 2008 and tested by Ziehl-Neelsen smear, MODS and Mycobacterial growth Indicator (MGIT, Becton Dickinson) culture. All samples sent by the treating clinician for testing were included in the analysis. An aliquot of processed sample deposit was stored at −20°C and tested in the present study by Xpert MTB/RIF test. 183 samples from 73 children were available for analysis by Xpert. Accuracy measures of MODS and Xpert were summarized.

Results

The sensitivity (%) in detecting children with a clinical diagnosis of TB for smear, MODS and Xpert were 37.9 [95% CI 25.5; 51.6], 51.7 [38.2; 65.0] and 50.0 [36.6; 63.4], respectively (per patient analysis). Xpert was significantly more sensitive than smear (P=0.046). Testing of additional samples did not increase case detection for MODS while testing of a second sputum sample by Xpert detected only two additional cases. The positive and negative predictive values (%) of Xpert were 100.0 [88.0; 100.0] and 34.1 [20.5; 49.9], respectively, while those of MODS were 96.8 [83.3; 99.9] and 33.3 [19.6; 49.5].

Conclusion

MODS culture and Xpert MTB/RIF test have similar sensitivities for the detection of pediatric TB. Xpert MTB RIF is able to detect tuberculosis and rifampicin resistance within two hours. MODS allows isolation of cultures for further drug susceptibility testing but requires approximately one week to become positive. Testing of multiple samples by xpert detected only two additional cases and the benefits must be considered against costs in each setting. Further research is required to evaluate the optimal integration of Xpert into pediatric testing algorithms.

【 授权许可】

   
2013 Nhu et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]Nelson LJ, Wells CD: Global epidemiology of childhood tuberculosis. Int J Tuberc Lung Dis 2004, 8(5):636-647.
• [2]Corbett EL, Watt CJ, Walker N, Maher D, Williams BG, Raviglione MC, Dye C: The growing burden of tuberculosis: global trends and interactions with the HIV epidemic. Arch Intern Med 2003, 163(9):1009-1021.
• [3]Zar HJ, Hanslo D, Apolles P, Swingler G, Hussey G: Induced sputum versus gastric lavage for microbiological confirmation of pulmonary tuberculosis in infants and young children: a prospective study. Lancet 2005, 365(9454):130-134.
• [4]Connell TG, Zar HJ, Nicol MP: Advances in the diagnosis of pulmonary tuberculosis in HIV-infected and HIV-uninfected children. J Infect Dis 2011, 204(Suppl 4):S1151-1158.
• [5]Marais BJ, Gie RP, Schaaf HS, Beyers N, Donald PR, Starke JR: Childhood pulmonary tuberculosis: old wisdom and new challenges. Am J Respir Crit Care Med 2006, 173(10):1078-1090.
• [6]Sandgren A, Cuevas LE, Dara M, Gie RP, Grzemska M, Hawkridge A, Hesseling AC, Kampmann B, Lienhardt C, Manissero D, et al.: Childhood tuberculosis: progress requires advocacy strategy now. Eur Respir J 2012, 40(2):294-297.
• [7]Marais BJ, Gie RP, Hesseling AC, Schaaf HS, Lombard C, Enarson DA, Beyers N: A refined symptom-based approach to diagnose pulmonary tuberculosis in children. Pediatrics 2006, 118(5):e1350-1359.
• [8]Graham SM, Ahmed T, Amanullah F, Browning R, Cardenas V, Casenghi M, Cuevas LE, Gale M, Gie RP, Grzemska M, et al.: Evaluation of tuberculosis diagnostics in children: 1. Proposed clinical case definitions for classification of intrathoracic tuberculosis disease. Consensus from an expert panel. J Infect Dis 2012, 205(suppl 2):S199-208.
• [9]Palomino JC: Current developments and future perspectives for TB diagnostics. Future Microbiol 2012, 7(1):59-71.
• [10]Moore DA, Evans CA, Gilman RH, Caviedes L, Coronel J, Vivar A, Sanchez E, Pinedo Y, Saravia JC, Salazar C, et al.: Microscopic-observation drug-susceptibility assay for the diagnosis of TB. N Engl J Med 2006, 355(15):1539-1550.
• [11]Ha DT, Lan NT, Wolbers M, Duong TN, Quang ND, Thi Van Thinh T, Thi Hong Ngoc L, Thi Ngoc Anh N, Van Quyet T, Thi Bich Tuyen N, et al.: Microscopic observation drug susceptibility assay (MODS) for early diagnosis of tuberculosis in children. PLoS One 2009, 4(12):e8341.
• [12]Oberhelman RA, Soto-Castellares G, Caviedes L, Castillo ME, Kissinger P, Moore DA, Evans C, Gilman RH: Improved recovery of Mycobacterium tuberculosis from children using the microscopic observation drug susceptibility method. Pediatrics 2006, 118(1):e100-106.
• [13]Blakemore R, Story E, Helb D, Kop J, Banada P, Owens MR, Chakravorty S, Jones M, Alland D: Evaluation of the analytical performance of the Xpert MTB/RIF assay. J Clin Microbiol 2010, 48(7):2495-2501.
• [14]Chang K, Lu W, Wang J, Zhang K, Jia S, Li F, Deng S, Chen M: Rapid and effective diagnosis of tuberculosis and rifampicin resistance with Xpert MTB/RIF assay: A meta-analysis. J Infect 2012, 64(6):580-588.
• [15]The Stop TB department WHO: Roadmap for rolling out Xpert MTB/RIFfor rapid diagnosis of TB and MDR-TB. 2010. available at http://www.who.int/tb/laboratory/roadmap_xpert_mtb-rif.pdf webcite
• [16]Nicol MP, Workman L, Isaacs W, Munro J, Black F, Eley B, Boehme CC, Zemanay W, Zar HJ: Accuracy of the Xpert MTB/RIF test for the diagnosis of pulmonary tuberculosis in children admitted to hospital in Cape Town, South Africa: a descriptive study. Lancet Infect Dis 2011, 11(11):819-824.
• [17]World Health Organisation: Global tuberculosis control. Geneva, Switzerland: World health Organisation; 2011. WHO/HTM/TB/2011.16
• [18]Population Division of the Department of Economic and Social Affairs of the United Nations Secretariat. World Population Prospects; The 2010 Revision. Accessed 28 May 2012. http://esa.un.org/unpd/wpp/index.htm webcite
• [19]World Health Organisation Global Tuberculosis Programme: Laboratory service in tuberculosis control: part II. Microscopy. Geneva, Switzerland: World Health Organisation; 1998. [WHO/TB/98258]
• [20]Becton Dickinson: BACTEC™ MGIT™ 960 SIRE kits for the antimycobacterial susceptibility testing of mycobacterium tuberculosis. Package insert. Revision: 2010/10 Accessed 28 May 2012. http://www.bd.com/ds/productCenter/245123.asp webcite
• [21]Agresti A, Caffo B: Simple and effective confidence intervals for proportions and difference of proportions result from adding two successes and two failures. Am Stat 2000, 54(4):280-288.
• [22]Rachow A, Clowes P, Saathoff E, Mtafya B, Michael E, Ntinginya EN, Kowour D, Rojas-Ponce G, Kroidl A, Maboko L, et al.: Increased and expedited case detection by xpert MTB/RIF assay in childhood tuberculosis: a prospective cohort study. Clin Infect Dis 2012, 54(10):1388-1396.
• [23]Swaminathan S, Rekha B: Pediatric tuberculosis: global overview and challenges. Clin Infect Dis 2010, 50(Suppl 3):S184-194.
• [24]Boehme CC, Nicol MP, Nabeta P, Michael JS, Gotuzzo E, Tahirli R, Gler MT, Blakemore R, Worodria W, Gray C, et al.: Feasibility, diagnostic accuracy, and effectiveness of decentralised use of the Xpert MTB/RIF test for diagnosis of tuberculosis and multidrug resistance: a multicentre implementation study. Lancet 2011, 377(9776):1495-1505.
• [25]Lawn SD, Brooks SV, Kranzer K, Nicol MP, Whitelaw A, Vogt M, Bekker LG, Wood R: Screening for HIV-associated tuberculosis and rifampicin resistance before antiretroviral therapy using the Xpert MTB/RIF assay: a prospective study. PLoS Med 2011, 8(7):e1001067.
• [26]Lawn SD, Nicol MP: Xpert(R) MTB/RIF assay: development, evaluation and implementation of a new rapid molecular diagnostic for tuberculosis and rifampicin resistance. Future Microbiol 2011, 6(9):1067-1082.