Diagnosing TB in HIV Co- infected PaAents Bob Belknap Denver Public Health
Disclosures No financial disclosures slides adapted from Dr. Michelle Haas
Session ObjecAves ParAcipants will be able to: 1. Reduce morbidity, mortality and TB transmission by making a rapid diagnosis of TB in HIV infected paaents 2. Provide appropriate treatment for TB- HIV co- infected paaents
Case 1 23 y/o originally from the DemocraAc Republic of Congo, in the United States for 6 years Presents to the emergency department (ED): cough for 5 days, subjecave fevers and chills Rx: 5 day course of azithromycin Symptoms did not improve and one week later he presented to the ED again
Case 1 1 st CXR
Case 1-2 nd CXR BP 100/60 P 105 RR 25 SpO2 92% RA, T 40.9 C DiaphoreAc, enlarged cervical lymph nodes and rales over the right mid lung Rapid HIV test posiave, CD4 60 cells/µl Cecriaxone, azithromycin and bactrim DS daily iniaated
Case 1 Cont d 23 y/o with AIDS and pneumonia unresponsive to outpaaent anabioacs Sputum for AFB TST IGRA Molecular tesang BAL What would you do?
Case 1 Cont d 23 y/o with AIDS and pneumonia unresponsive to outpaaent anabioacs What would you do? Sputum for AFB negaave x 3 TST - negaave IGRA negaave (QFT) Molecular tesang not done BAL smear negaave
Case 1 Cont d Respiratory isola-on discon-nued AnAbioAcs broadened to vancomycin and cefepime Suspicion for TB decreased and concern grew for lymphoma conanued daily fevers to 41 C.
Case 1 Cont d MediasAnoscopy on hospital day 13 purulence Broadened anabioacs further to meropenem, linezolid and voriconazole AFB+ from mediasanal lymph node Assue on day 14 Started isoniazid, rifampin, pyrazinamide, and ethambutol (remaining anabioacs disconanued) 29 days a(er ini-al presenta-on M. tuberculosis probe posi-ve 4 days later
This is our world hmp://www.worldmapper.org Copyright Sasi Group (University of Sheffield) and Mark Newman (University of Michigan), used with permission
Our world on TB hmp://www.worldmapper.org Copyright Sasi Group & Benjamin D. Hennig (University of Sheffield), used with permission
The CriAcal First Step Consider TB in the Differen0al 1. Risks for infec0on (foreign- born) 2. Risks for progression (HIV/AIDS) 3. Concerning symptoms
TB Symptoms Typical Cough > 3 weeks Weight loss Night sweats Fever Hemoptysis Atypical Recurrent pneumonia or UTIs (cx neg) PleuriAc chest pain Swollen lymph nodes Headache or altered mental status Pathologic fractures Unexplained anemia InferAlity
TB in HIV- infected PaAents 80 70 60 50 40 30 20 10 0 HIV- posiave HIV- negaave J Trop Med Hygiene 1993;96:1-11
Clinical manifestaaons of TB in HIV- infected Decreasing CD4 count increases likelihood of: Accelerated progression of disease Disseminated disease LymphadeniAs Mycobacteremia Central nervous system Sepsis syndrome Cavitary disease less common Increased findings of diffuse infiltrates, consolidaaon Conversely, can have subclinical disease Shafer RW, et al. Medicine (Baltimore), 1991. 70(6): 384-97 Greenberg SD, et al. Radiology. 1994;193(1):115 Gray JM and Cohn DL. Semin Respir Crit Care Med. 2013 Feb;34(1):32-43. Corbett EL, et al., Am J Respir Crit Care Med. 2004;170(6):673 Jacob ST, et al., PLoS One. 2013 Aug 5;8(8):e70305. Cain KP, et al., N Engl J Med 2010;362(8):707 716
ReacAvaAon TB in HIV- infected by CD4 Cases 2014 Denver per Public 100/person- years Health
Diagnosing TB in HIV CXR insensiave, may have normal findings in up to 1/3 (AFB) sputum smear Up to 70% may be AFB smear negaave at presentaaon No difference in sensiavity of bronchoalveolar lavage (BAL) over sputum inducaon (SI) N=44, sensiavity of SI=36%, BAL=40% AFB sputum culture gold standard, limit of detecaon 10 organisms/ml sputum Conde MB. Am J Respir Crit Care Med. 2000;162(6):2238 Bakari M, et al., BMC Infect Dis. 2008;8:32 Hassim S, et al., Clin Infect Dis. 2010;50(7):1053 Steingart KR, et al., Lancet Infect Dis, 2006. 6: 664-74
Diagnosing TB in HIV AFB blood cultures Common bloodstream infecaon in HIV infected paaents living in high TB burden countries Urine culture for AFB Yield up to 77% Interferon- gamma release assays SensiAvity for idenafying acave TB approximately 61% Arthur, G., et al.,clin Infect Dis, 2001. 33(2): p. 248-56 Varma, J.K., et al., Emerg Infect Dis, 2010. 16(10): p. 1569-75 Shafer RW, et al., Medicine (Baltimore), 1991. 70(6): 384-97 Theron G, et al., Am J Respir Crit Care Med, 2011. 184: 132-140. Yoon C, et al., PLoS One 2012 Santin M, et al., PLoS 2012;7(3):e32482
Gene Xpert MTB/RIF Xpert : nucleic acid amplificaaon test (NAAT) to detect M. tuberculosis May detect up to 67% of AFB smear negaave cases SensiAvity may be lower in HIV- infected individuals with smear negaave disease: 42-55% SensiAvity may be lower in low- burden sevngs: 29% among smear negaave ambulatory TB suspects in Montreal Varma, J.K., et al., Emerg Infect Dis, 2010. 16(10): p. 1569-75 Theron G, et al., Am J Respir Crit Care Med, 2011. 184: 132-140. Yoon C, et al., PLoS One 2012 Santin M, et al., PLoS 2012;7(3):e32482 Sohh H, et al. CID 2014;58(7):970 6 MMWR 2013;62: 821-828 Chaissson, LH et al. CID 2014; doi: 10.1093/cid/ciu620
Diagnosing TB in HIV Clinical suspicion remains criacal Rapid diagnosacs are improving but the sensiavity is lower in HIV- infected paaents Disseminated disease is common - AFB blood and urine cultures can be useful for definiavely diagnosing When the clinical suspicion is high, empiric TB treatment should be strongly considered: 1. Reduces morbidity and mortality 2. Decreases risk of transmission