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TB Grand Rounds

Sheila Nolan, MD, W. Kemper Alston, MD, & Barbara Watson, MD

June 26, 2007

Speaker: Sheila Nolan, MD

Infectious disease fellow at Children’s Hospital of Philadelphia (CHOP)Medical degree, Temple UniversityPediatric residency, University of South Florida

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A neonate with A neonate with respiratory distressrespiratory distress

Sheila M. Nolan, MDSheila M. Nolan, MDInfectious Diseases FellowInfectious Diseases FellowThe ChildrenThe Children’’s Hospital of s Hospital of PhiladelphiaPhiladelphia

Admission HistoryAdmission History

•• Patient is a 36 day old exPatient is a 36 day old ex--32 week 32 week male admitted to CHOP for male admitted to CHOP for worsening respiratory distressworsening respiratory distress

•• Baby was a 2050gm IVF product born Baby was a 2050gm IVF product born via SVD to a 30 y/o G3P0 mom via SVD to a 30 y/o G3P0 mom •• RPR negative, HIV negative, RPR negative, HIV negative, HBsAgHBsAg and GBS and GBS

unknownunknown•• Pregnancy complicated by prePregnancy complicated by pre--term laborterm labor•• Maternal h/o hypothyroid Maternal h/o hypothyroid dxdx –– on on synthroidsynthroid

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Admission HistoryAdmission History

•• Baby had an unremarkable NICU course Baby had an unremarkable NICU course until approximately 3 wks of ageuntil approximately 3 wks of age•• Noted to be lethargic and began having Noted to be lethargic and began having

episodes of episodes of desaturationdesaturation•• CXR showed right sided infiltrateCXR showed right sided infiltrate•• Over the next 2 weeks the baby had Over the next 2 weeks the baby had

progressively worsening CXR and progressively worsening CXR and respiratory distress, eventually requiring respiratory distress, eventually requiring intubationintubation and mechanical ventilationand mechanical ventilation

•• Transferred to CHOP Transferred to CHOP

Further historyFurther history•• Upon development of respiratory Upon development of respiratory

distress, patient had blood distress, patient had blood cxcx’’ssdrawn and an LPdrawn and an LP–– CxCx’’ss all negative, multiple repeat blood all negative, multiple repeat blood

cxcx’’ss all negativeall negative•• He was initially started on He was initially started on ampicillinampicillin, ,

gentamicingentamicin and and cefotaximecefotaxime–– Tracheal aspirate Tracheal aspirate cxcx grew grew EnterobacterEnterobacter

aerogenesaerogenes–– Antibiotics changed to Antibiotics changed to VancomycinVancomycin, ,

CefepimeCefepime and and amikacinamikacin

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Social and Family Social and Family HistoryHistory•• Parents originally from India, father Parents originally from India, father

traveled to India 6 months ago, mom traveled to India 6 months ago, mom has not been there in few yearshas not been there in few years

•• Grandparents arrived shortly after Grandparents arrived shortly after baby was delivered and have visited baby was delivered and have visited the NICU frequentlythe NICU frequently–– Grandmother has been coughing since Grandmother has been coughing since

arrivalarrival•• Parents deny any family history of Parents deny any family history of

health problemshealth problems

Physical ExamPhysical Exam•• Temp: 36.7, HR: 167, RR: 50, BP: 73/39Temp: 36.7, HR: 167, RR: 50, BP: 73/39•• Wt: 3340gmWt: 3340gm•• General: Lethargic, decreased tone, mildly General: Lethargic, decreased tone, mildly

edematousedematous•• HEENT: AFOSF, palate intactHEENT: AFOSF, palate intact•• Chest: coarse BS, crackles throughoutChest: coarse BS, crackles throughout•• Heart: RRR, 2+ pulsesHeart: RRR, 2+ pulses•• Abdomen: +BS, soft, NT, no HSM Abdomen: +BS, soft, NT, no HSM •• G/U: Tanner I male, testes descended b/lG/U: Tanner I male, testes descended b/l•• Extremities: MAEE, no hip clickExtremities: MAEE, no hip click•• NeuroNeuro: + grasp, low tone: + grasp, low tone

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Laboratory DataLaboratory Data•• WBC 14.9, WBC 14.9, HgbHgb 13.7, 13.7, HctHct 39.8, 39.8, PltPlt 159159

–– Diff: 1 Diff: 1 myelocytemyelocyte, 1 , 1 metamyelocytemetamyelocyte, 29 bands, 41 , 29 bands, 41 neutrophilsneutrophils, 20 lymphocytes, 8 , 20 lymphocytes, 8 monocytesmonocytes

•• Na 120, K 4.8, Na 120, K 4.8, ClCl 85, 85, BicarbBicarb 31, BUN 5, Cr 31, BUN 5, Cr 0.3, 0.3, GluGlu 85, Ca 8.8, Mg 1.7, 85, Ca 8.8, Mg 1.7, PhosPhos 4.44.4

•• Total Total bilibili 1.1, 1.1, UnconjugatedUnconjugated bilibili 1.1, Total 1.1, Total protein 4.5, Albumin 2.1, ALT 38, AST 88protein 4.5, Albumin 2.1, ALT 38, AST 88

•• pH 7.471, CO2 46.1, O2 37, pH 7.471, CO2 46.1, O2 37, BicarbBicarb 33.6, 33.6, Base excess 9Base excess 9

Laboratory DataLaboratory Data

•• CSF: CSF: –– WBC 0 WBC 0 –– RBC 0 RBC 0 –– Protein 66 Protein 66 –– Glucose 43 Glucose 43 –– gram stain gram stain –– rare WBC, no organisms rare WBC, no organisms –– cxcx –– negneg

•• Viral respiratory panel Viral respiratory panel –– negative negative •• PertussisPertussis PCR PCR -- negativenegative

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Chest XChest X--RayRay

Diffuse bilateral parenchymal infiltrates

Microbiology DataMicrobiology Data

•• Routine Blood Routine Blood cxcx: no growth: no growth•• Routine Urine Routine Urine cxcx: no growth: no growth•• Tracheal aspirate:Tracheal aspirate:

–– Gram stain: moderate Gram stain: moderate WBCWBC’’ss, few , few beaded gram positive rods beaded gram positive rods –– acid acid fast positivefast positive

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AFB Smear of Tracheal AFB Smear of Tracheal AspirateAspirate

http://commons.wikimedia.org/wiki/Image:Mycobacterium_tuberculosis_Ziehl-Neelsen_stain_02.jpg

AFB Smear and Culture AFB Smear and Culture ResultsResults

PCR and culture confirmed Mycobacterium tuberculosisPCR and culture confirmed Mycobacterium tuberculosis

----CSFCSF

++++Tracheal Tracheal aspirateaspirate

----UrineUrine++--Blood Blood

++++Gastric Gastric AspirateAspirate

CultureCultureSmearSmearSpecimenSpecimen

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Hospital CourseHospital Course

•• He was initially too ill to receive oral He was initially too ill to receive oral medication, so was started on a 5 medication, so was started on a 5 drug IV regimendrug IV regimen–– INHINH–– RifampinRifampin–– AmikacinAmikacin–– LinezolidLinezolid–– Ciprofloxacin Ciprofloxacin

Hospital CourseHospital Course

•• Hospital day 5, dopamine was Hospital day 5, dopamine was weanedweaned

•• Within 1 week, he began NG feedsWithin 1 week, he began NG feeds•• By the 2By the 2ndnd week after the initiation of week after the initiation of

therapy, the baby was therapy, the baby was extubatedextubated and and tolerating full feeds. Antibiotic tolerating full feeds. Antibiotic regimen was switched to an oral regimen was switched to an oral medications: medications: –– INH, INH, RifampinRifampin, , EthambutolEthambutol and and

PyrazinamidePyrazinamide

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Discharge XDischarge X--rayray

CXR prior to discharge. Baby was discharged to home 3 ½ weeks after admission

InvestigationInvestigation

•• TSTTST’’ss were administered on parents were administered on parents and grandparents and chest xand grandparents and chest x--rays rays obtainedobtained–– TST resultsTST results

•• Father Father –– 7mm7mm•• Mother Mother –– 1010--12 mm12 mm•• Grandparents reported as negative per PMDGrandparents reported as negative per PMD

–– Chest xChest x--rays all read as negativerays all read as negative

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InvestigationInvestigation

•• Mother reported that while she was Mother reported that while she was in India being evaluated for infertility in India being evaluated for infertility she had an endometrial biopsy that she had an endometrial biopsy that was negative for TBwas negative for TB

•• After BabyAfter Baby’’s TB PCR confirmation, s TB PCR confirmation, mothermother’’s OB performed a D&C and s OB performed a D&C and the the endometriumendometrium was + for AFBwas + for AFB

•• Formalin fixed placental specimens Formalin fixed placental specimens were stained for AFB and were were stained for AFB and were negative negative

Questions & CommentsQuestions & Comments

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Genital TuberculosisGenital Tuberculosis•• Reportedly causes 7Reportedly causes 7--56% of infertility 56% of infertility

in developing countriesin developing countries•• Endometrial aspirates and biopsies Endometrial aspirates and biopsies

often negative for AFB smear and often negative for AFB smear and culture, PCR may be more usefulculture, PCR may be more useful

•• PPD often negative, 55% sensitivity, PPD often negative, 55% sensitivity, 80% specificity 80% specificity

•• Organs most frequently affectedOrgans most frequently affected–– Fallopian tubes 95Fallopian tubes 95--100%100%–– EndometriumEndometrium 5050--60%60%–– Ovaries 20Ovaries 20--30%30%

Genital TuberculosisGenital Tuberculosis

Hysterosalpingogram of a patient with tuberculosis of the fallopian tubes shows right-sided hydrosalpinx with an occluded left fallopian tube

http://www.gfmer.ch/selected_images_v2/detail_list.php?cat1=7&cat3=592&stype=d

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Tuberculosis Tuberculosis SalpingitisSalpingitis

http://www.gfmer.ch/selected_images_v2/detail_list.php?cat1=7&cat3=592&stype=d

Congenital TuberculosisCongenital Tuberculosis

•• Rare, postRare, post--natal acquired TB is much natal acquired TB is much more commonmore common

•• Acquired via Acquired via hematogenoushematogenous spread spread through umbilical vein from an through umbilical vein from an infected placenta or aspiration or infected placenta or aspiration or ingestion of infected amniotic fluidingestion of infected amniotic fluid

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Congenital TuberculosisCongenital Tuberculosis

•• Usually presents in first 2Usually presents in first 2--4 weeks of 4 weeks of lifelife–– Can range from first few days up to 4 Can range from first few days up to 4

monthsmonths•• Clinical manifestations include fever, Clinical manifestations include fever,

respiratory distress, abdominal respiratory distress, abdominal distension, lethargy, irritability, distension, lethargy, irritability, hepatosplenomegalyhepatosplenomegaly, , lymphadenopathylymphadenopathy, jaundice, ear , jaundice, ear discharge and skin papules discharge and skin papules

Discussion Discussion

•• TB diagnosis and evaluation in TB diagnosis and evaluation in neonates and infantsneonates and infants

•• Treatment of neonatal TBTreatment of neonatal TB

•• Other questions & comments?Other questions & comments?

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DNA Fingerprinting ResultsDNA Fingerprinting Results

ReferencesReferences•• ChowdhuryChowdhury NN. Overview of Tuberculosis of the female genital NN. Overview of Tuberculosis of the female genital

tract. J Indian Med Assoc. 1996 Sep;94(9):345tract. J Indian Med Assoc. 1996 Sep;94(9):345--6, 361.6, 361.•• JindalJindal UN. An algorithmic approach to female genital tuberculosis UN. An algorithmic approach to female genital tuberculosis

causing infertility. causing infertility. IntInt J J TubercTuberc Lung Dis. 2006 Sep;10(9):1045Lung Dis. 2006 Sep;10(9):1045--50.50.•• KiniKini PG. Congenital tuberculosis associated with maternal PG. Congenital tuberculosis associated with maternal

asymptomatic endometrial tuberculosis. Ann Trop asymptomatic endometrial tuberculosis. Ann Trop PaediatrPaediatr. 2002 . 2002 Jun;22(2):179Jun;22(2):179--81.81.

•• NamavarNamavar JB, et al. Female genital tuberculosis and infertility. JB, et al. Female genital tuberculosis and infertility. IntInt J J GynaecolGynaecol ObstetObstet. 2001 Dec;75(3):269. 2001 Dec;75(3):269--72.72.

•• Parikh FR, et al. Genital tuberculosis Parikh FR, et al. Genital tuberculosis –– a major pelvic factor a major pelvic factor causing infertility in Indian women. causing infertility in Indian women. FertilFertil SterilSteril. 1997 Mar;67(3): . 1997 Mar;67(3): 497497--500.500.

•• RautRaut VS, et al. The VS, et al. The MantouxMantoux test in the diagnosis of genital test in the diagnosis of genital tuberculosis in women. tuberculosis in women. IntInt J J GynaecolGynaecol ObstetObstet. 2001 Feb; . 2001 Feb; 72(2):16572(2):165--9.9.

•• SkevakiSkevaki CL, CL, KafetzisKafetzis DA. Tuberculosis in neonates and infants: DA. Tuberculosis in neonates and infants: epidemiology, pathogenesis, clinical manifestations, diagnosis, epidemiology, pathogenesis, clinical manifestations, diagnosis, and and management issues. management issues. PaediatrPaediatr Drugs. 2005;7(4): 219Drugs. 2005;7(4): 219--34.34.

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Discharge & FollowDischarge & Follow--upup

Speaker: W. Kemper Alston, MD, MPH

TB Medical Consultant for Vermont Department of HealthAssociate Professor of Medicine at University of Vermont- College of MedicineAttending Physician of ID Unit, Hospital Epidemiologist, Chairman of Infection Control Committee, & Employee Health Service Consultant at Fletcher Allen Health Care

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“Empyema Necessitatis”

W. Kemper Alston, MD, MPHFletcher Allen Health Care

University of VermontBurlington, Vermont

Patient History

77 year-old male referred to ID Clinic on 8/24/05 by his primary care because of a large, painful, fluctuant, left posterior chest wall massComplained of pain over his left chest (anterior, lateral, and posterior) for 2 monthsTreated with azithromycin in early 8/05, then was seen in a local ER

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Past Medical History

Severe, oxygen-dependent, chronic lung disease. Followed by Pulmonary. Described at times as obstructive, restrictive, bronchiectatic, fibrotic, & hypercapneicDiabetes, hyperlipidemia, PUD, CHF, and anemiaReview of systems: Sweats, weight loss, SOB, cough, & difficulty urinating (all chronic). No fever, GI complaints, rash, or neurological complaints

Medications & Social History

Simvastatin, glyburide, tamsulosin, metformin, lansoprazole, furosemide, fluticasone/salmeterol, & albuterol/ipratropiumHad a steroid taper in 5/05Allergic to sulfaLives at home with his wifeFormer smoker. No alcohol

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Physical Examination

Chronically ill-appearing, in a wheelchair, on supplemental oxygen with labored respirations. Afebrile, 77.5 kg, BP 130/58, pulse 110/min., respirations 22/min., 93% saturation on 4 liters/minDecreased breath sounds throughout, with bronchial breath sounds at left apex. Exam of chest wall…

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Laboratory Data

ER 8/8/05: WBC 13.88/18/05: WBC 11.4, HCT 34%, Plat 349K, ESR 96CXR & CT scan…

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Diagnostic Work-up

Sono-guided aspirate of the lesion was performed on 8/11/05:– Cytology: Inflammatory; no malignancy– Gram stain: Polys, no organisms– Bacterial culture: Negative– AFB smear negative, culture pending– Fungal stain negative, culture pending

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OK, there is more history…

Mother and brother had tuberculosisDiagnosed with TB as a teenager, in the 1940s. Presumably pulmonary and pleural diseaseHe was in and out of the Pittsford Sanatorium in Pittsford, VT between 1941 and 1945, where he was treated with arsenic dropsHe had empyema, draining thru the chest wall, and chest tubes…

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Pittsford Sanatorium

Pittsford Sanatorium

Built in 1907. The site was chosen because it was believed to receive the most sunshine in Vermont. The first patient was admitted 12/16/1907In 1917 the mean LOS was 141 daysIn May, 1971 it was turned over to the VT State Police as a training facilityThe building is said to be haunted by one it’s former nurses

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More History

In approximately 1971 he was treated with 1 year of INH alone by PulmonarySputum AFB was negative at that timeHis wife is TST negative

Clinical Course

The fluid culture from 8/05 grew M. tuberculosisSeen in follow-up 9/29/05 and begun on INH, rifampin, PZA & B6Baseline LFTs normalOn 10/20/05 sensitivities returned resistant to INH, sensitive to rifampin, ethambutol, and PZAINH was changed to ethambutol

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Questions & Comments

Clinical Course

Tolerated meds well, with normal LFTs, but a large, fluctuant collection persistedAspirated again for relief of symptoms in 10/05, 12/05, and 3/06 (1st two not cultured, the last was culture negative)CT scan 7/27/06 with 7 x 3 cm. fluid collectionTreated until 9/30/06Seen 11/17/06 and was doing well

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Clinical Course

Admitted to local hospital 4/18-25/07 with presumed COPD exacerbation (fatigue, cough, and dyspnea)CXR was unchangedSonogram revealed no drainable fluid collectionSputum x3 smear and culture negativePersistent monocytosis (50%)Seen 5/1/07 and doing well…

Empyema Necessitatis

The accumulation of pus in the pleural cavity, with subsequent rupture into the surrounding soft tissue. Drainage may occur into the breast, bronchus, mediastinum, esophagus, diaphragm, pericardium or retroperitoneum. Pus may even reach the flank, groin or thigh. Before antibiotics became available, empyema necessitatis was a complication of tuberculosis, fungal infections and various forms of pneumonia.

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Empyema Necessitatis

The spontaneous extension of pus through the parietal pleura and chest wall from an empyema with the formation of a subcutaneous abscess. In most circumstances this occurs secondary to a tuberculous empyema. There may be an associated bronchopleural fistula.

NEJM Volume 352:e8 March 3, 2005 Number 9

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Discussion

Reactivation disease 60 years after treatment in a sanatoriumThe impact of INH monotherapy in the setting of untreated TB diseaseManagement of INH resistanceManagement of “empyema necessitatis” in someone who is clearly not a surgical candidateThe association of monocytosis with TB

Speaker: Barbara Watson, MD

Medical Director for the Immunization Program & Associate Director of TB Control Program at Philadelphia Department of Public Health

Responsible for all issues related to pediatric TB

Associate Professor of Pediatrics at Jefferson Medical College

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Is this Rassmussen’s aneurysm?

Barbara Watson, MDPediatric ConsultantTB Control Program

Philadelphia Department of Public Health

Patient History

16 year old US born Hispanic malePresents with 7 month history of cough, night sweats, fever, including hemoptysis 1 month prior to admissionHospitalized Dec. 15, 2006 to Jan. 24, 2007Admitting diagnosis – hemoptysis – unknown causeTuberculin skin test – “positive”Discharge diagnosis –sinusitisPatient referred to TB clinicTST repeated at TB clinic and read as negativeOn 2-12-07, CHOP reported to TB Control that sputum smear AFB positive Patient continued to have hemoptysis

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Social History

Substance abuse – Marijuana cigarettes 5-7 daily

5 sexual partnersHistory of juvenile detention

Physical Exam

Vitals – Temp 37.4, Pulse 68, RR=20, BP 107/70, Pulse ox 98% on room airPertinent physical findings – no nasal congestion, adenopathyNormal PE

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Laboratory Results

CBC – Hb 16.4, Hct 44.5, WCC 9.9 –segs70, lymphs 20, plt –280

HIV – negative

LFTs - ALT 26, AST 31

RPR negative

Radiographic Findings

CXR – nodule RULCT scan revealed RUL nodular densities and ground glass opacities, not visualized on CXRAngiography with no evidence of aneurysmNormal pulmonary function tests

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Bacteriology

Specimens obtained at CHOP– Sputum x3 – AFB negative, culture grew

MAI– Bronchoscopy – BAL – many WCC, no

orgs, CMV and RSV, AFB negativeSpecimens obtained at TB clinic– Induced specimens x3 – AFB positive,

culture pending

Treatment Course

Treatment regimen -RIPE

Start- 2-9-06

Directly observed therapy (DOT)

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Treatment Course Cont’d

Cough severity improvedContinuing to complain of hemoptysis– Small amounts blood witnessed by DSI and

at clinic visitCough, night sweats, and chills eventually resolved

Rassmussen’s Aneurysm

van den Heuvel and van RensburgOctober 2006 NEJM 355 (16): e17 Images in clinical medicine54 male with past history of TB and hemoptysis

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Rassmussen’s Aneurysm

NEJM 2006

Ongoing problem list in 3-07

Issue with court date for car theftPolice call re contagiousnessAFB – culture - ? MAI onlyOn 4-10-07, MRI showed normal pulmonary arteries, aortaAbove procedure delayed court issues

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Discussion

Lessons learned– Need timely discharge records from

hospitals especially in patients with social risk factors who play games

Questions for the audience - TB or not TB?

Thank you!!