Tuberculosis EvaluationTuberculosis Evaluationin the Underserved Community in the Underserved Community

John W. Wilson, MDJohn W. Wilson, MD

Division of Infectious DiseasesDivision of Infectious Diseases

Mayo Clinic, RochesterMayo Clinic, Rochester

Estimated TB incidence rate, 2006Estimated TB incidence rate, 2006

Estimated new TB cases (all forms) per 100 000 population

The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries.

Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. WHO 2006. All rights reserved

No estimate

0-24

50-99

300 or more

25-49

100-299

Estimated HIV prevalence in new TB cases, 2006Estimated HIV prevalence in new TB cases, 2006

No estimate

0–4

20–49

50 or more

5–19

HIV prevalence in TB cases, (%)

The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries.

Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. WHO 2006. All rights reserved

Approx. 50 CountriesApprox. 50 Countries

Common Lack of Medical Common Lack of Medical Resources in 3Resources in 3rdrd World Setting World Setting

Typically unavailable or not done:Typically unavailable or not done:• Mycobacterial culturesMycobacterial cultures• Drug susceptibility/resistance testingDrug susceptibility/resistance testing• Tuberculin skin testingTuberculin skin testing

• High % positive – from TB infection and / High % positive – from TB infection and / or prior BCG vaccinationor prior BCG vaccination

Limited availabilityLimited availability• CXR – if hospital / clinic accessibleCXR – if hospital / clinic accessible• 22ndnd-line TB drugs-line TB drugs• Directly Observed Therapy (DOT)Directly Observed Therapy (DOT)

Standard Components of TB/TLBI Standard Components of TB/TLBI Evaluation in USA / UKEvaluation in USA / UK

• Patient HistoryPatient History• SymptomsSymptoms• PMHx, comorbiditiesPMHx, comorbidities• FHx and patient demographicsFHx and patient demographics

• Physical examinationPhysical examination

• Radiologic evaluationRadiologic evaluation• CXR, CTCXR, CT

• Laboratory testingLaboratory testing• TST, QFNTST, QFN• If available: CBC, LFTs, Tissue histology, culturesIf available: CBC, LFTs, Tissue histology, cultures

A New ApproachA New Approach to TB Investigation in to TB Investigation in Underserved Location:Underserved Location:

4 Steps to Success:4 Steps to Success:

1.1. The The HostHost

2.2. The The SyndromeSyndrome

3.3. The The MicrobiologyMicrobiology

4.4. The The TreatmentTreatment

Defining / characterizing:Defining / characterizing:

11stst - Define the Host - Define the Host

Defining the HostDefining the Host

• Immunocompetent vs. Immunosuppressed Immunocompetent vs. Immunosuppressed – **– **Especially HIV statusEspecially HIV status

• Higher rates of primary TB diseaseHigher rates of primary TB disease• More atypical pulmonary findingsMore atypical pulmonary findings• Higher rates of extrapulmonary disease & Higher rates of extrapulmonary disease &

disseminationdissemination

• Other medical Other medical comorbiditiescomorbidities: Diabetes: Diabetes

• Adult Adult vs. vs. ChildChild

• Living statusLiving status: community vs., hospital, jail, : community vs., hospital, jail, shelter etc.shelter etc.

• Other cases of TB reported, pattern of Other cases of TB reported, pattern of spread?spread?

Adult: Reactivation Pulmonary TBAdult: Reactivation Pulmonary TB

More common presentation in immunocompetent, HIV-neg. adultsMore common presentation in immunocompetent, HIV-neg. adults

Typical Symptoms - Typical Symptoms - nonspecificnonspecific::

Dry, NP coughDry, NP cough Chest pain, pleurisyChest pain, pleurisy

HemoptysisHemoptysis DyspneaDyspnea

HoarsenessHoarseness Constitutional Constitutional symptoms:symptoms:

(malaise, feverish, (malaise, feverish, sweats, weight sweats, weight

loss)loss)

Predilection for Predilection for upper lung zonesupper lung zones

CXR of Pulmonary TB Disease – CXR of Pulmonary TB Disease – ReactivationReactivation

Typically in Typically in Immunocompetent AdultImmunocompetent Adult

• Location:Location: apical and/or posterior segment of RUL; apical and/or posterior segment of RUL; apicoposterior segment of LUL or superior apicoposterior segment of LUL or superior segment of either lower lobesegment of either lower lobe

• Infiltrate:Infiltrate: fibronodular, irregular with variable fibronodular, irregular with variable coalescence and cavitationcoalescence and cavitation

• Cavities:Cavities: thick, moderately irregular walls thick, moderately irregular walls

• Volume loss:Volume loss: progressive, can be rapid progressive, can be rapid

PLEASE NOTE:PLEASE NOTE:

• **“Atypical” lung findings in approx. 1/3 patients**“Atypical” lung findings in approx. 1/3 patients

• **Infiltrates can appear anywhere!!**Infiltrates can appear anywhere!!

Presentation of TB Presentation of TB Commonly DifferentCommonly Different in in HIV / Immunosuppressed PtsHIV / Immunosuppressed Pts

TB in an immunosuppressed patient TB in an immunosuppressed patient

• Can be more of a “Systemic” illnessCan be more of a “Systemic” illness

• More More extrapulmonary involvementextrapulmonary involvement - up to - up to 60% cases in HIV (+) pts:60% cases in HIV (+) pts:

• More atypical presentations:More atypical presentations:• DiarrheaDiarrhea• HepatosplenomegalyHepatosplenomegaly• LymphadenopathyLymphadenopathy

Pulmonary TB with immunosuppressionPulmonary TB with immunosuppression

• CXR findings - advanced HIV/AIDS (CXR findings - advanced HIV/AIDS (variable):variable):• Confluent pneumoniaConfluent pneumonia• Lower zone infiltratesLower zone infiltrates• Hilar / paratracheal adenopathyHilar / paratracheal adenopathy• Risk for Miliary spread / patternRisk for Miliary spread / pattern

• ““Primary Complex patternPrimary Complex pattern” common with ” common with HIV/AIDSHIV/AIDS

• Hilar adenopathyHilar adenopathy• Lower / mid lung infiltrates, unilateralLower / mid lung infiltrates, unilateral• Pleural effusionsPleural effusions

Tuberculin skin testing & HIV infectionTuberculin skin testing & HIV infection

• Reactivity of TST decreases as CD4 count Reactivity of TST decreases as CD4 count decreases:decreases:

• 15-25% false-neg. (-)15-25% false-neg. (-) in normal host (HIV in normal host (HIV neg.) with pulmonary TB (disease)neg.) with pulmonary TB (disease)

• 50-90% false-neg. (-)50-90% false-neg. (-) in pts. with early HIV (no in pts. with early HIV (no other OI’s)other OI’s)

• 80-100% false-neg. (-)80-100% false-neg. (-) in pts. with advanced in pts. with advanced HIVHIV

• In USA/UK, consider preventative INH therapy for In USA/UK, consider preventative INH therapy for HIV & immunosupp. pts regardless of TST for:HIV & immunosupp. pts regardless of TST for:

• Close contacts to “infectious” casesClose contacts to “infectious” cases

Clinical Presentations of Pediatric TB is NOT the Clinical Presentations of Pediatric TB is NOT the same as with Adult TBsame as with Adult TB

Distinction between TB infection and disease more Distinction between TB infection and disease more clear in adult than in children / infantsclear in adult than in children / infants

Adult:Adult: disease usually follows disease usually follows reactivationreactivation of of previously dormant organisms and almost always previously dormant organisms and almost always havehave

• Significant symptoms and CXR abnormalities.Significant symptoms and CXR abnormalities.

• Infants & children:Infants & children: disease more often disease more often complicates complicates initial “primary” infectioninitial “primary” infection

• CXR findings can be subtle and symptoms are lacking CXR findings can be subtle and symptoms are lacking in up to 50% childrenin up to 50% children

• Typically lower MTB burden - Less contagious; AFB Typically lower MTB burden - Less contagious; AFB smear commonly negativesmear commonly negative

Manifestations of Primary Pulmonary Manifestations of Primary Pulmonary TB in childrenTB in children

• Hilar or mediastinal Hilar or mediastinal adenopathyadenopathy

• Paucity of SSx Paucity of SSx relative to CXRrelative to CXR

• Usually no cavitiesUsually no cavities

22ndnd - Define the Syndrome - Define the Syndromethe the “-itis”“-itis”

Define the Syndrome – the Define the Syndrome – the “itis”“itis”

• Pneumonitis – clinical sx’s or via CXR?Pneumonitis – clinical sx’s or via CXR?

• Lymphadenitis, meningitis / cerebritis, Lymphadenitis, meningitis / cerebritis, pericarditis, hepatitis, peritonitis, pericarditis, hepatitis, peritonitis, pyelonephritis, etc.pyelonephritis, etc.

Is the syndrome consistent with TB?Is the syndrome consistent with TB?

Is this new vs. recurrent TB?Is this new vs. recurrent TB?

Is drug-resistant TB possible? Prev trx?Is drug-resistant TB possible? Prev trx?

Treatment approaches based the syndrome Treatment approaches based the syndrome – not all the same– not all the same

Considerations Depending upon the Type of Considerations Depending upon the Type of Tuberculosis – Tuberculosis – “The Syndrome”“The Syndrome”

• InfectiousnessInfectiousness to others – more of a to others – more of a concern with pulmonary diseaseconcern with pulmonary disease

• Role of Role of SteroidsSteroids – meningeal and – meningeal and pericardial diseasepericardial disease

• ExtensionsExtensions in duration of therapy – in duration of therapy – e.g. bone/joint (vertebral), CNS TBe.g. bone/joint (vertebral), CNS TB

• Presentations of Presentations of IRISIRIS

Miliary TuberculosisMiliary Tuberculosis

Lymphatic TB (Scrofula)Lymphatic TB (Scrofula)

Pleural TBPleural TB

Pleural TB – Advanced, calcifiedPleural TB – Advanced, calcified

Genitourinary TBGenitourinary TB

Pericardial TBPericardial TB

CXR Residuals of Primary InfectionCXR Residuals of Primary Infection(without progression to disease)(without progression to disease)

• Apical / bi-apical fibronodular shadowing Apical / bi-apical fibronodular shadowing (“Simon (“Simon foci”)foci”)

• high risk for reactivation or postprimary-type TBhigh risk for reactivation or postprimary-type TB

• Ghon focusGhon focus = isolated small fibrocalcific lesions = isolated small fibrocalcific lesions (usually > 1 yr.)(usually > 1 yr.)

• site of primary pulmonary infectionsite of primary pulmonary infection• no increased risk of reactivationno increased risk of reactivation

• Ranke’s complexRanke’s complex = dense calcified hilar LN with = dense calcified hilar LN with ipsilateral Ghon lesion (calcified)ipsilateral Ghon lesion (calcified)

• no increased risk of reactivationno increased risk of reactivation

• Other findings - no increased risk of reactivationOther findings - no increased risk of reactivation• thickening of apical pleurathickening of apical pleura• blunting of costophrenic sulcusblunting of costophrenic sulcus

Risk of Tuberculosis (disease) Risk of Tuberculosis (disease) after untreated MTB infectionafter untreated MTB infection

• Normal adults: 5-10% Normal adults: 5-10% in lifetimein lifetime

• HIV infected adults: 7-10% HIV infected adults: 7-10% per yearper year

• Older children: 5-10% (delayed)Older children: 5-10% (delayed)

• Infants: Infants: 40% in 1-2 years40% in 1-2 years

33rdrd - Define the Microbiology - Define the Microbiology

Either confirmed or suspectedEither confirmed or suspected

Defining the MicrobiologyDefining the MicrobiologyQuestions to consider:Questions to consider:

1.1. Is it Infection vs. Non-infection-driven Is it Infection vs. Non-infection-driven inflammation?inflammation?

If infection presentIf infection present::

2.2. Is the Infection mycobacterial, Is the Infection mycobacterial, bacterial, fungal , viral, protozoan, bacterial, fungal , viral, protozoan, helminthic?helminthic?

- AFB staining, KOH, Gram staining on sputum - AFB staining, KOH, Gram staining on sputum smear or tissue? smear or tissue? • Easily done in most laboratories; rapid resultsEasily done in most laboratories; rapid results

Defining the MicrobiologyDefining the Microbiology

3.3. Is the infection caused by Is the infection caused by M. tuberculosisM. tuberculosis vs. Non TB mycobacteria (NTM)?vs. Non TB mycobacteria (NTM)?

• Presumptive TB in endemic regions and by Presumptive TB in endemic regions and by clinical presentationclinical presentation

• Mycobacteria cultures, probes and PCR Mycobacteria cultures, probes and PCR usually not availableusually not available in 3 in 3rdrd world setting world setting

4.4. Drug susceptible vs. resistance (single Drug susceptible vs. resistance (single drug, MDR, XDR-TB)drug, MDR, XDR-TB)

• Often based on Often based on previous treatment and previous treatment and responseresponse (or lack of response) (or lack of response)

**** Note: MTB may not be confirmed when Note: MTB may not be confirmed when starting therapystarting therapy

Diagnostic Considerations in HIV (+) Diagnostic Considerations in HIV (+) pts with MTB Diseasepts with MTB Disease

• Sputum smear and culture somewhat less Sputum smear and culture somewhat less sensitive in HIV (+) ptssensitive in HIV (+) pts

• May be 2May be 2° ° to decrease tendency for to decrease tendency for cavitary disease (less organism load)cavitary disease (less organism load)

• May need to collect additional sputum May need to collect additional sputum samples; consider gastric and urine samples; consider gastric and urine samples samples – if resources available– if resources available

• In USA - consider MTB probes on In USA - consider MTB probes on smear negative sputum samplessmear negative sputum samples

44thth - Define the Treatment - Define the Treatment

TB Treatment in Underserved Community – TB Treatment in Underserved Community – Need to referNeed to refer to Regional TB treatment to Regional TB treatment

center / cliniccenter / clinic

• TB Drug availability TB Drug availability

• AFB monitoringAFB monitoring

• CXR availabilityCXR availability

• DOTS (if available)DOTS (if available)

• Isolation (if Isolation (if applicable) – applicable) – depending upon depending upon settingsetting

Anti-Tuberculosis DrugsAnti-Tuberculosis Drugs

11stst Line Drugs Line Drugs

• IsoniazidIsoniazid

• RifamycinRifamycin•Rifampin Rifampin •RifabutinRifabutin•RifapentineRifapentine

• PyrazinamidePyrazinamide

• EthambutolEthambutol

22ndnd Line Drugs Line Drugs

• AminoglycosidesAminoglycosides•Streptomycin; Amikacin & Streptomycin; Amikacin &

KanamycinKanamycin

• CapreomycinCapreomycin

• ThioamidesThioamides•EthionamideEthionamide•ProthionamideProthionamide

• FluoroquinolonesFluoroquinolones•LevofloxacinLevofloxacin•MoxifloxacinMoxifloxacin•CiprofloxacinCiprofloxacin

• Cycloserine (and Terizidone)Cycloserine (and Terizidone)

• Para-Aminosalicylic Acid (PAS)Para-Aminosalicylic Acid (PAS)

Treatment of Pulmonary TBTreatment of Pulmonary TBPrograms may vary by countryPrograms may vary by country

Option 1:Option 1:

Initiation: INH, RFP, PZA, EMB Initiation: INH, RFP, PZA, EMB dailydaily x x 8wks8wks

Continuation: INH, RFP Continuation: INH, RFP dailydaily or or 2-3x/wk2-3x/wk DOT x DOT x 16 wks16 wks

Option 2:Option 2:

Initiation: INH, RFP, PZA, EMB Initiation: INH, RFP, PZA, EMB dailydaily x x 2 wks2 wks, then, then

INH, RFP, PZA, EMB INH, RFP, PZA, EMB 2x/wk2x/wk DOT x DOT x 6 wks6 wks

Continuation: INH, RFP Continuation: INH, RFP 2x/wk2x/wk x x 16 wks16 wks DOT DOT

Option 3:Option 3:

INH, RFP, PZA, EMB INH, RFP, PZA, EMB 3x/wk3x/wk DOT x DOT x 6 months6 months

Special circumstances:Special circumstances:

a) Pts. who cannot take PZA: INH, RFP x a) Pts. who cannot take PZA: INH, RFP x 99 monthsmonths • EMB or SM added initially unless EMB or SM added initially unless resist. Risk 2x/wk dosing can be resist. Risk 2x/wk dosing can be

given after 1-2 mo. if isolate sensitivegiven after 1-2 mo. if isolate sensitive

b) Pregnancy: INH, RFP, EMB x b) Pregnancy: INH, RFP, EMB x 9 months 9 months (PZA avoided in USA)(PZA avoided in USA)

THE ENDTHE ENDThank you for your attentionThank you for your attention

All of the following are common challenges All of the following are common challenges with the diagnosis and management of with the diagnosis and management of

Tuberculosis in underserved regions Tuberculosis in underserved regions EXCEPTEXCEPT

1 2 3 4 5

4%9%

21%

64%

3%

1.1. Mycobacteria cultures commonly not Mycobacteria cultures commonly not availableavailable

2.2. Drug susceptibility testing usually not Drug susceptibility testing usually not availableavailable

3.3. High rates of HIV-MTB co-infectionHigh rates of HIV-MTB co-infection

4.4. First-line TB treatment drugs usually not First-line TB treatment drugs usually not availableavailable

5.5. Directly observed therapy (DOT) Directly observed therapy (DOT) recommended but commonly not utilizedrecommended but commonly not utilized