Rapid microbiological screening for tuberculosis in HIV-positive patients on the first day of acute hospital admission by systematic testing of urine samples using Xpert MTB/RIF: a prospective cohort in South Africa

BMC Medicine

Graeme Meintjes²  Mark P. Nicol⁵  Pearl Pahlana⁴  Monica Vogt⁴  Gavin van Wyk¹  Charlotte Schutz²  Rosie Burton³  Andrew D. Kerkhoff⁷  Stephen D. Lawn⁶ 

[1] GF Jooste Hospital, Manenberg, Cape Town, South Africa;Clinical Infectious Diseases Research Initiative, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa;Khayelitsha District Hospital, Cape Town, South Africa;The Desmond Tutu HIV Centre, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa;Division of Medical Microbiology and Institute for Infectious Diseases and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa;Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa;Department of Global Health, Academic Medical Center, Amsterdam Institute for Global Health and Development, University of Amsterdam, Amsterdam, The Netherlands

关键词: Africa;    Xpert;    Urine;    Screening;    Diagnosis;    HIV;    Extrapulmonary;    Pulmonary;    Tuberculosis;   

Others  :  1222374
DOI  :  10.1186/s12916-015-0432-2

 received in 2015-06-22, accepted in 2015-07-22,  发布年份 2015

【 摘 要 】

Background

Autopsy studies of HIV/AIDS-related hospital deaths in sub-Saharan Africa reveal frequent failure of pre-mortem diagnosis of tuberculosis (TB), which is found in 34–64 % of adult cadavers. We determined the overall prevalence and predictors of TB among consecutive unselected HIV-positive adults requiring acute hospital admission and the comparative diagnostic yield obtained by screening urine and sputum samples obtained on day 1 of admission with Xpert MTB/RIF (Xpert).

Methods

To determine overall TB prevalence accurately, comprehensive clinical sampling (sputum, urine, blood plus other relevant samples) was done and TB was defined by detection of Mycobacterium tuberculosis in any sample using Xpert and/or mycobacterial liquid culture. To evaluate a rapid screening strategy, we compared the diagnostic yield of Xpert testing sputum samples and urine samples obtained with assistance from a respiratory study nurse in the first 24 h of admission.

Results

Unselected HIV-positive acute adult new medical admissions (n = 427) who were not receiving TB treatment were enrolled irrespective of clinical presentation or symptom profile. From 2,391 cultures and Xpert tests done (mean, 5.6 tests/patient) on 1,745 samples (mean, 4.1 samples/patient), TB was diagnosed in 139 patients (median CD4 cell count, 80 cells/μL). TB prevalence was very high (32.6 %; 95 % CI, 28.1–37.2 %; 139/427). However, patient symptoms and risk factors were poorly predictive for TB. Overall, ≥1 non-respiratory sample(s) tested positive in 115/139 (83 %) of all TB cases, including positive blood cultures in 41/139 (29.5 %) of TB cases. In the first 24 h of admission, sputum (spot and/or induced samples) and urine were obtainable from 37.0 % and 99.5 % of patients, respectively (P <0.001). From these, the proportions of total TB cases (n = 139) that were diagnosed by Xpert testing sputum, urine or both sputum and urine combined within the first 24 h were 39/139 (28.1 %), 89/139 (64.0 %) and 108/139 (77.7 %) cases, respectively (P <0.001).

Conclusions

The very high prevalence of active TB and its non-specific presentation strongly suggest the need for routine microbiological screening for TB in all HIV-positive medical admissions in high-burden settings. The incremental diagnostic yield from Xpert testing urine was very high and this strategy might be used to rapidly screen new admissions, especially if sputum is difficult to obtain.

【 授权许可】

   
2015 Lawn et al.

【 图 表 】

Fig. 1.

Fig. 2.

Fig. 3.

【 参考文献 】

• [1]World Health Organization (WHO). Global tuberculosis report 2014. Geneva: WHO; 2014. Available at: http://apps.who.int/iris/bitstream/10665/137094/1/9789241564809_eng.pdf?ua=1. Accessed 31 July 2015.
• [2]Gupta RK, Lucas SB, Fielding KL, Lawn SD. Prevalence of tuberculosis in post-mortem studies of HIV-infected adults and children in resource-limited settings: a systematic review and meta-analysis. AIDS 2015; in press.
• [3]Lucas SB, Hounnou A, Peacock C, Beaumel A, Djomand G, N'Gbichi JM et al.. The mortality and pathology of HIV infection in a west African city. AIDS. 1993; 7:1569-79.
• [4]Rana FS, Hawken MP, Mwachari C, Bhatt SM, Abdullah F, Ng'ang'a LW et al.. Autopsy study of HIV-1-positive and HIV-1-negative adult medical patients in Nairobi, Kenya. J Acquir Immune Defic Syndr. 2000; 24:23-9.
• [5]Cohen T, Murray M, Wallengren K, Alvarez GG, Samuel EY, Wilson D. The prevalence and drug sensitivity of tuberculosis among patients dying in hospital in KwaZulu-Natal, South Africa: a postmortem study. PLoS Med. 2010; 7: Article ID e1000296
• [6]Cox JA, Lukande RL, Nelson AM, Mayanja-Kizza H, Colebunders R, Van Marck E et al.. An autopsy study describing causes of death and comparing clinico-pathological findings among hospitalized patients in Kampala, Uganda. PLoS One. 2012; 7: Article ID e33685
• [7]Wong EB, Omar T, Setlhako GJ, Osih R, Feldman C, Murdoch DM et al.. Causes of death on antiretroviral therapy: a post-mortem study from South Africa. PLoS One. 2012; 7: Article ID e47542
• [8]World Health Organization (WHO). WHO tuberculosis programme framework for effective tuberculosis control. Geneva: WHO; 1994. WHO/TB/94.179. Available at: http://whqlibdoc.who.int/hq/1994/WHO_TB_94.179.pdf. Accessed 31 July 2015.
• [9]Reid MJ, Shah NS. Approaches to tuberculosis screening and diagnosis in people with HIV in resource-limited settings. Lancet Infect Dis. 2009; 9:173-84.
• [10]Lawn SD, Wood R. Tuberculosis in antiretroviral treatment services in resource-limited settings: addressing the challenges of screening and diagnosis. J Infect Dis. 2011; 204:S1159-67.
• [11]World Health Organization (WHO). Tuberculosis diagnostics automated DNA test. WHO endorsement and recommendations. Geneva: WHO; 2010. Available at: http://www.who.int/tb/features_archive/xpert_factsheet.pdf. Accessed 31 July 2015.
• [12]World Health Organization (WHO). Xpert MTB/RIF assay for the diagnosis of pulmonary and extrapulmonary TB in adults and children: policy update. WHO/HTM/TB/2013.16. Geneva: WHO; 2013. Accessible at: http://apps.who.int/iris/bitstream/10665/112472/1/9789241506335_eng.pdf?ua=1. Accessed 31 July 2015.
• [13]Denkinger CM, Schumacher SG, Boehme CC, Dendukuri N, Pai M, Steingart KR. Xpert MTB/RIF assay for the diagnosis of extrapulmonary tuberculosis: a systematic review and meta-analysis. Eur Respir J. 2014; 44:435-46.
• [14]Maynard-Smith L, Larke N, Peters JA, Lawn SD. Diagnostic accuracy of the Xpert MTB/RIF assay for extrapulmonary and pulmonary tuberculosis when testing non-respiratory samples: a systematic review. BMC Infect Dis. 2014; 14:709. BioMed Central Full Text
• [15]Lawn SD, Kerkhoff AD, Vogt M, Wood R. High diagnostic yield of tuberculosis from screening urine samples from HIV-infected patients with advanced immunodeficiency using the Xpert MTB/RIF assay. J Acquir Immune Defic Syndr. 2012; 60:289-94.
• [16]Peter JG, Theron G, Muchinga TE, Govender U, Dheda K. The diagnostic accuracy of urine-based Xpert MTB/RIF in HIV-infected hospitalized patients who are smear-negative or sputum scarce. PLoS One. 2012; 7: Article ID e39966
• [17]Getahun H, Kittikraisak W, Heilig CM, Corbett EL, Ayles H, Cain KP et al.. Development of a standardized screening rule for tuberculosis in people living with HIV in resource-constrained settings: individual participant data meta-analysis of observational studies. PLoS Med. 2011; 8: Article ID e1000391
• [18]Lawn SD, Kerkhoff AD, Vogt M, Wood R. Diagnostic accuracy of a low-cost, urine antigen, point-of-care screening assay for HIV-associated pulmonary tuberculosis before antiretroviral therapy: a descriptive study. Lancet Infect Dis. 2012; 12:201-9.
• [19]Lawn SD, Brooks SV, Kranzer K, Nicol MP, Whitelaw A, Vogt M et al.. Screening for HIV-associated tuberculosis and rifampicin resistance before antiretroviral therapy using the Xpert MTB/RIF assay: a prospective study. PLoS Med. 2011; 8: Article ID e1001067
• [20]World Health Organization (WHO). Haemoglobin concentrations for the diagnosis of anaemia and assessment of severity. WHO/NMH/NHD/MNM/11.1. Geneva: WHO; 2011. Accessible at: http://www.who.int/vmnis/indicators/haemoglobin.pdf. Accessed 31 July 2015.
• [21]Friedrich SO, Rachow A, Saathoff E, Singh K, Mangu CD, Dawson R et al.. Assessment of the sensitivity and specificity of Xpert MTB/RIF assay as an early sputum biomarker of response to tuberculosis treatment. Lancet Respir Med. 2013; 1:462-70.
• [22]Lawn SD, Kranzer K, Edwards DJ, McNally M, Bekker LG, Wood R. Tuberculosis during the first year of antiretroviral therapy in a South African cohort using an intensive pretreatment screening strategy. AIDS. 2010; 24:1323-8.
• [23]Bassett IV, Wang B, Chetty S, Giddy J, Losina E, Mazibuko M et al.. Intensive tuberculosis screening for HIV-infected patients starting antiretroviral therapy in Durban, South Africa. Clin Infect Dis. 2010; 51:823-9.
• [24]Houlihan CF, Mutevedzi PC, Lessells RJ, Cooke GS, Tanser FC, Newell ML. The tuberculosis challenge in a rural South African HIV programme. BMC Infect Dis. 2010; 10:23. BioMed Central Full Text
• [25]Bates M, O'Grady J, Mwaba P, Chilukutu L, Mzyece J, Cheelo B et al.. Evaluation of the burden of unsuspected pulmonary tuberculosis and co-morbidity with non-communicable diseases in sputum producing adult inpatients. PLoS One. 2012; 7: Article ID e40774
• [26]Lawn SD, Kerkhoff AD, Pahlana P, Vogt M, Wood R. Diagnostic yield of tuberculosis using sputum induction in HIV-positive patients before antiretroviral therapy. Int J Tuberc Lung Dis. 2012; 16:1354-7.
• [27]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; 6:1067-82.
• [28]Blakemore R, Story E, Helb D, Kop J, Banada P, Owens MR et al.. Evaluation of the analytical performance of the Xpert MTB/RIF assay. J Clin Microbiol. 2010; 48:2495-501.
• [29]Shafer RW, Kim DS, Weiss JP, Quale JM. Extrapulmonary tuberculosis in patients with human immunodeficiency virus infection. Medicine (Baltimore). 1991; 70:384-97.
• [30]Lawn SD. Point-of-care detection of lipoarabinomannan (LAM) in urine for diagnosis of HIV-associated tuberculosis: a state of the art review. BMC Infect Dis. 2012; 12:103. BioMed Central Full Text
• [31]Lawn SD, Kerkhoff AD, Vogt M, Wood R. Clinical significance of lipoarabinomannan detection in urine using a low-cost point-of-care diagnostic assay for HIV-associated tuberculosis. AIDS. 2012; 26:1635-43.
• [32]Talbot E, Munseri P, Teixeira P, Matee M, Bakari M, Lahey T et al.. Test characteristics of urinary lipoarabinomannan and predictors of mortality among hospitalized HIV-infected tuberculosis suspects in Tanzania. PLoS One. 2012; 7: Article ID e32876
• [33]Lanjewar DN. The spectrum of clinical and pathological manifestations of AIDS in a consecutive series of 236 autopsied cases in Mumbai, India. Patholog Res Int. 2011; 2011:547618.