Predictors and outcomes of mycobacteremia among HIV-infected smear- negative presumptive tuberculosis patients in Uganda

BMC Infectious Diseases

Yukari C Manabe³  Susan E Dorman³  Jerrold J Ellner¹  Moses L Joloba⁴  Harriet Mayanja-Kizza⁴  Maunank Shah³  Bruce J Kirenga⁴  Molly Holshouser³  Derek Armstrong³  Damalie Nakanjako⁴  Willy Ssengooba²  Lydia Nakiyingi⁴ 

[1] Boston Medical Center, Boston University School of Medicine, Boston, MA, USA;Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands;Johns Hopkins University School of Medicine, Baltimore, MD, USA;Makerere University College of Heath Sciences, Kampala, Uganda

关键词: Sub-Saharan Africa;    LAM;    HIV;    Smear- negative;    Bacteremia;    Mycobacterial infections;    Mortality;    Predictors;   

Others  :  1127130
DOI  :  10.1186/s12879-015-0812-4

 received in 2015-01-22, accepted in 2015-02-09,  发布年份 2015

【 摘 要 】

Background

Sputum smear microscopy for tuberculosis (TB) diagnosis lacks sensitivity in HIV-infected symptomatic patients and increases the likelihood that mycobacterial infections particularly disseminated TB will be missed; delays in diagnosis can be fatal. Given the duration for MTB growth in blood culture, clinical predictors of MTB bacteremia may improve early diagnosis of mycobacteremia. We describe the predictors and mortality outcome of mycobacteremia among HIV-infected sputum smear-negative presumptive TB patients in a high prevalence HIV/TB setting.

Methods

Between January and November 2011, all consenting HIV-infected adults suspected to have TB (presumptive TB) were consecutively enrolled. Diagnostic assessment included sputum smear microscopy, urine Determine TB lipoarabinomannan (LAM) antigen test, mycobacterial sputum and blood cultures, chest X-ray, and CD4 cell counts in addition to clinical and socio-demographic data. Patients were followed for 12 months post-enrolment.

Results

Of 394 sputum smear-negative participants [female, 63.7%; median age (IQR) 32 (28–39) years], 41/394 (10.4%) had positive mycobacterial blood cultures (mycobacteremia); all isolates were M. tuberculosis (MTB). The median CD4 cell count was significantly lower among patients with mycobacteremia when compared with those without (CD4 31 versus 122 cells/μL, p < 0.001). In a multivariate analysis, male gender [OR 3.4, 95%CI (1.4-7.6), p = 0.005], CD4 count <100 cells/μL [OR 3.1, 95% CI (1.1-8.6), p = 0.030] and a positive lateral flow urine TB LAM antigen test [OR 15.3, 95%CI (5.7-41.1), p < 0.001] were significantly associated with mycobacteremia. At 12 months of follow-up, a trend towards increased mortality was observed in patients that were MTB blood culture positive (35.3%) compared with those that were MTB blood culture negative (23.3%) (p = 0.065).

Conclusions

Mycobacteremia occurred in 10% of smear-negative patients and was associated with higher mortality compared with smear-negative patients without mycobacteremia. Advanced HIV disease (CD4 < 100 cells/mm³), male gender and positive lateral flow urine TB LAM test predicted mycobacteremia in HIV-infected smear-negative presumptive TB patients in this high prevalence TB/HIV setting.

【 授权许可】

   
2015 Nakiyingi et al.; licensee BioMed Central.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]Frieden TR, Sterling TR, Munsiff SS, Watt CJ, Dye C: Tuberculosis. Lancet 2003, 362(9387):887-99.
• [2]Harries AD, Hargreaves NJ, Kemp J, Jindani A, Enarson DA, Maher D, et al.: Deaths from tuberculosis in sub-Saharan African countries with a high prevalence of HIV-1. Lancet 2001, 357(9267):1519-23.
• [3]Corbett EL, Watt CJ, Walker N, Maher D, Williams BG, Raviglione MC, et al.: The growing burden of tuberculosis: global trends and interactions with the HIV epidemic. Arch Intern Med 2003, 163(9):1009-21.
• [4]Getahun H, Gunneberg C, Granich R, Nunn P: HIV infection-associated tuberculosis: the epidemiology and the response. Clin Infect Dis 2010, 50(Suppl 3):S201-7.
• [5]Colebunders R, Bastian I: A review of the diagnosis and treatment of smear-negative pulmonary tuberculosis. Int J Tuberc Lung Dis 2000, 4(2):97-107.
• [6]Apers L, Wijarajah C, Mutsvangwa J, Chigara N, Mason P, van der Stuyft P: Accuracy of routine diagnosis of pulmonary tuberculosis in an area of high HIV prevalence. Int J Tuberc Lung Dis 2004, 8(8):945-51.
• [7]Nunn PP, Elliott AM, McAdam KP: Tropical respiratory medicine. 2. Impact of human immunodeficiency virus on tuberculosis in developing countries. Thorax 1994, 49(5):511-8.
• [8]Elliott AM, Namaambo K, Allen BW, Luo N, Hayes RJ, Pobee JO, et al.: Negative sputum smear results in HIV-positive patients with pulmonary tuberculosis in Lusaka. Zambia Tuber Lung Dis 1993, 74(3):191-4.
• [9]Hargreaves NJ, Kadzakumanja O, Whitty CJ, Salaniponi FM, Harries AD, Squire SB: 'Smear-negative' pulmonary tuberculosis in a DOTS programme: poor outcomes in an area of high HIV seroprevalence. Int J Tuberc Lung Dis 2001, 5(9):847-54.
• [10]Henegar C, Behets F, Vanden Driessche K, Tabala M, Bahati E, Bola V, et al.: Mortality among tuberculosis patients in the Democratic Republic of Congo. Int J Tuberc Lung Dis 2012, 16(9):1199-204.
• [11]Macpherson P, Dimairo M, Bandason T, Zezai A, Munyati SS, Butterworth AE, et al.: Risk factors for mortality in smear-negative tuberculosis suspects: a cohort study in Harare. Zimbabwe Int J Tuberc Lung Dis 2011, 15(10):1390-6.
• [12]Ssali FN, Kamya MR, Wabwire-Mangen F, Kasasa S, Joloba M, Williams D, et al.: A prospective study of community-acquired bloodstream infections among febrile adults admitted to Mulago Hospital in Kampala, Uganda. J Acquir Immune Defic Syndr Hum Retrovirol 1998, 19(5):484-9.
• [13]Archibald LK, McDonald LC, Nwanyanwu O, Kazembe P, Dobbie H, Tokars J, et al.: A hospital-based prevalence survey of bloodstream infections in febrile patients in Malawi: implications for diagnosis and therapy. J Infect Dis 2000, 181(4):1414-20.
• [14]Crump JA, Ramadhani HO, Morrissey AB, Saganda W, Mwako MS, Yang LY, et al.: Bacteremic disseminated tuberculosis in sub-saharan Africa: a prospective cohort study. Clin Infect Dis 2012, 55(2):242-50.
• [15]Reddy EA, Shaw AV, Crump JA: Community-acquired bloodstream infections in Africa: a systematic review and meta-analysis. Lancet Infect Dis 2010, 10(6):417-32.
• [16]Jacob ST, Pavlinac PB, Nakiyingi L, Banura P, Baeten JM, Morgan K, et al.: Mycobacterium tuberculosis bacteremia in a cohort of hiv-infected patients hospitalized with severe sepsis in uganda-high frequency, low clinical suspicion [corrected] and derivation of a clinical prediction score. PLoS One 2013, 8(8):e70305.
• [17]Kethireddy S, Light RB, Mirzanejad Y, Maki D, Arabi Y, Lapinsky S, et al.: Mycobacterium tuberculosis Septic Shock. Chest 2013, 144(2):474-82.
• [18]McDonald LC, Archibald LK, Rheanpumikankit S, Tansuphaswadikul S, Eampokalap B, Nwanyanawu O, et al.: Unrecognised Mycobacterium tuberculosis bacteraemia among hospital inpatients in less developed countries. Lancet 1999, 354(9185):1159-63.
• [19]Harries AD: Unrecognised Mycobacterium tuberculosis. Lancet 2000, 355(9198):142. author reply 142–143
• [20]Grinsztejn B, Fandinho FC, Veloso VG, Joao EC, Lourenco MC, Nogueira SA, et al.: Mycobacteremia in patients with the acquired immunodeficiency syndrome. Arch Intern Med 1997, 157(20):2359-63.
• [21]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(3):e33685.
• [22]Archibald LK, Reller LB: Clinical microbiology in developing countries. Emerg Infect Dis 2001, 7(2):302-5.
• [23]Crump JA, Morrissey AB, Ramadhani HO, Njau BN, Maro VP, Reller LB: Controlled comparison of BacT/Alert MB system, manual Myco/F lytic procedure, and isolator 10 system for diagnosis of Mycobacterium tuberculosis Bacteremia. J Clin Microbiol 2011, 49(8):3054-7.
• [24]Hanscheid T, Monteiro C, Cristino JM, Lito LM, Salgado MJ: Growth of Mycobacterium tuberculosis in conventional BacT/ALERT FA blood culture bottles allows reliable diagnosis of Mycobacteremia. J Clin Microbiol 2005, 43(2):890-1.
• [25]Nakiyingi L, Moodley VM, Manabe YC, Nicol MP, Holshouser M, Armstrong DT, et al.: Diagnostic accuracy of a rapid urine lipoarabinomannan test for tuberculosis in HIV-infected adults. J Acquir Immune Defic Syndr 2014, 66(3):270-279.
• [26]Infectious Diseases Institute Annual report; Infectious Diseases Institute, College of Health sciences Makerere University. http://idi.mak.ac.ug. In.; 2012.
• [27]Uganda Ministry of Health Manual of the National Tuberculosis and Leprosy Programme, 2nd Edition, 2010. http://www.who.int/hiv/pub/guidelines/uganda_tb.pdf, downloaded on 2nd January 2014.
• [28]Cox JA, Lukande RL, Lucas S, Nelson AM, Van Marck E, Colebunders R: Autopsy causes of death in HIV-positive individuals in sub-Saharan Africa and correlation with clinical diagnoses. AIDS Rev 2010, 12(4):183-94.
• [29]Lewis DK, Peters RP, Schijffelen MJ, Joaki GR, Walsh AL, Kublin JG, et al.: Clinical indicators of mycobacteraemia in adults admitted to hospital in Blantyre, Malawi. Int J Tuberc Lung Dis 2002, 6(12):1067-74.
• [30]Peacock D, Redpath J, Weston M, Evans K, Daub A, Greig A, et al. Literature review on men, gender, health and HIV and AIDS in South Africa. Sonke Gender Justice Network 2008. http://menengage.org/wpcontent/uploads/2014/06/Male_attitudes_to_HIVAIDS_and_health_issues_in_South_Africa.pdf, downloaded on 7th January 2015
• [31]Shah M, Martinson NA, Chaisson RE, Martin DJ, Variava E, Dorman SE: Quantitative analysis of a urine-based assay for detection of lipoarabinomannan in patients with tuberculosis. J Clin Microbiol 2010, 48(8):2972-4.
• [32]Manabe YC, Nonyane BA, Nakiyingi L, Mbabazi O, Lubega G, Shah M, et al.: Point-of-care lateral flow assays for tuberculosis and cryptococcal antigenuria predict death in HIV infected adults in Uganda. PLoS One 2014, 9(7):e101459.