1、Tuberculosis Evaluation in the Underserved Community,John W. Wilson, MD Division of Infectious Diseases Mayo Clinic, Rochester,Estimated 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
2、 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
3、 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, 2006,No estimate,04,2049,50 or more,519,HIV prevalence in TB cases, (%),The boundaries and names shown and the designations used on thi
4、s 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 approximat
5、e border lines for which there may not yet be full agreement. WHO 2006. All rights reserved,Approx. 50 Countries,Common Lack of Medical Resources in 3rd World Setting,Typically unavailable or not done: Mycobacterial cultures Drug susceptibility/resistance testing Tuberculin skin testing High % posit
6、ive from TB infection and / or prior BCG vaccination Limited availability CXR if hospital / clinic accessible 2nd-line TB drugs Directly Observed Therapy (DOT),Standard Components of TB/TLBI Evaluation in USA / UK,Patient History Symptoms PMHx, comorbidities FHx and patient demographics Physical exa
7、mination Radiologic evaluation CXR, CT Laboratory testing TST, QFN If available: CBC, LFTs, Tissue histology, cultures,A New Approach to TB Investigation in Underserved Location: 4 Steps to Success:,The Host The Syndrome The Microbiology The Treatment,Defining / characterizing:,1st - Define the Host
8、,Defining the Host,Immunocompetent vs. Immunosuppressed *Especially HIV status Higher rates of primary TB disease More atypical pulmonary findings Higher rates of extrapulmonary disease & dissemination Other medical comorbidities: Diabetes Adult vs. Child Living status: community vs., hospital, jail
9、, shelter etc. Other cases of TB reported, pattern of spread?,Adult: Reactivation Pulmonary TB,More common presentation in immunocompetent, HIV-neg. adults Typical Symptoms - nonspecific:Dry, NP cough Chest pain, pleurisyHemoptysis DyspneaHoarseness Constitutional symptoms:(malaise, feverish, sweats
10、, weight loss) Predilection for upper lung zones,CXR of Pulmonary TB Disease Reactivation Typically in Immunocompetent Adult,Location: apical and/or posterior segment of RUL; apicoposterior segment of LUL or superior segment of either lower lobe Infiltrate: fibronodular, irregular with variable coal
11、escence and cavitation Cavities: thick, moderately irregular walls Volume loss: progressive, can be rapidPLEASE NOTE: *“Atypical” lung findings in approx. 1/3 patients *Infiltrates can appear anywhere!,Presentation of TB Commonly Different in HIV / Immunosuppressed Pts,TB in an immunosuppressed pati
12、ent Can be more of a “Systemic” illness More extrapulmonary involvement - up to 60% cases in HIV (+) pts: More atypical presentations: Diarrhea Hepatosplenomegaly Lymphadenopathy,Pulmonary TB with immunosuppression,CXR findings - advanced HIV/AIDS (variable): Confluent pneumonia Lower zone infiltrat
13、es Hilar / paratracheal adenopathy Risk for Miliary spread / pattern “Primary Complex pattern” common with HIV/AIDS Hilar adenopathy Lower / mid lung infiltrates, unilateral Pleural effusions,Tuberculin skin testing & HIV infection,Reactivity of TST decreases as CD4 count decreases: 15-25% false-neg
14、. (-) in normal host (HIV neg.) with pulmonary TB (disease) 50-90% false-neg. (-) in pts. with early HIV (no other OIs) 80-100% false-neg. (-) in pts. with advanced HIVIn USA/UK, consider preventative INH therapy for HIV & immunosupp. pts regardless of TST for: Close contacts to “infectious” cases,C
15、linical Presentations of Pediatric TB is NOT the same as with Adult TB,Distinction between TB infection and disease more clear in adult than in children / infants Adult: disease usually follows reactivation of previously dormant organisms and almost always have Significant symptoms and CXR abnormali
16、ties. Infants AFB smear commonly negative,Manifestations of Primary Pulmonary TB in children,Hilar or mediastinal adenopathy Paucity of SSx relative to CXR Usually no cavities,2nd - Define the Syndrome the “-itis”,Define the Syndrome the “itis”,Pneumonitis clinical sxs or via CXR? Lymphadenitis, men
17、ingitis / cerebritis, pericarditis, hepatitis, peritonitis, pyelonephritis, etc.Is the syndrome consistent with TB? Is this new vs. recurrent TB? Is drug-resistant TB possible? Prev trx? Treatment approaches based the syndrome not all the same,Considerations Depending upon the Type of Tuberculosis “
18、The Syndrome”,Infectiousness to others more of a concern with pulmonary disease Role of Steroids meningeal and pericardial disease Extensions in duration of therapy e.g. bone/joint (vertebral), CNS TB Presentations of IRIS,Miliary Tuberculosis,Lymphatic TB (Scrofula),Pleural TB,Pleural TB Advanced,
19、calcified,Genitourinary TB,Pericardial TB,CXR Residuals of Primary Infection (without progression to disease),Apical / bi-apical fibronodular shadowing (“Simon foci”) high risk for reactivation or postprimary-type TB Ghon focus = isolated small fibrocalcific lesions (usually 1 yr.) site of primary p
20、ulmonary infection no increased risk of reactivation Rankes complex = dense calcified hilar LN with ipsilateral Ghon lesion (calcified) no increased risk of reactivation Other findings - no increased risk of reactivation thickening of apical pleura blunting of costophrenic sulcus,Risk of Tuberculosi
21、s (disease) after untreated MTB infection,Normal adults: 5-10% in lifetime HIV infected adults: 7-10% per year Older children: 5-10% (delayed) Infants: 40% in 1-2 years,3rd - Define the Microbiology,Either confirmed or suspected,Defining the Microbiology Questions to consider:,Is it Infection vs. No
22、n-infection-driven inflammation? If infection present: 2. Is the Infection mycobacterial, bacterial, fungal , viral, protozoan, helminthic?- AFB staining, KOH, Gram staining on sputum smear or tissue? Easily done in most laboratories; rapid results,Defining the Microbiology,3. Is the infection cause
23、d by M. tuberculosis vs. Non TB mycobacteria (NTM)? Presumptive TB in endemic regions and by clinical presentation Mycobacteria cultures, probes and PCR usually not available in 3rd world setting 4. Drug susceptible vs. resistance (single drug, MDR, XDR-TB) Often based on previous treatment and resp
24、onse (or lack of response) * Note: MTB may not be confirmed when starting therapy,Diagnostic Considerations in HIV (+) pts with MTB Disease,Sputum smear and culture somewhat less sensitive in HIV (+) pts May be 2 to decrease tendency for cavitary disease (less organism load) May need to collect addi
25、tional sputum samples; consider gastric and urine samples if resources available In USA - consider MTB probes on smear negative sputum samples,4th - Define the Treatment,TB Treatment in Underserved Community Need to refer to Regional TB treatment center / clinic,TB Drug availability AFB monitoring C
26、XR availability DOTS (if available) Isolation (if applicable) depending upon setting,Anti-Tuberculosis Drugs,1st Line Drugs Isoniazid Rifamycin Rifampin Rifabutin Rifapentine Pyrazinamide Ethambutol,2nd Line Drugs Aminoglycosides Streptomycin; Amikacin & Kanamycin Capreomycin Thioamides Ethionamide
27、Prothionamide Fluoroquinolones Levofloxacin Moxifloxacin Ciprofloxacin Cycloserine (and Terizidone) Para-Aminosalicylic Acid (PAS),Treatment of Pulmonary TB Programs may vary by country,Option 1:Initiation: INH, RFP, PZA, EMB daily x 8wksContinuation: INH, RFP daily or 2-3x/wk DOT x 16 wks Option 2:
28、Initiation: INH, RFP, PZA, EMB daily x 2 wks, thenINH, RFP, PZA, EMB 2x/wk DOT x 6 wksContinuation: INH, RFP 2x/wk x 16 wks DOT Option 3: INH, RFP, PZA, EMB 3x/wk DOT x 6 months Special circumstances: a) Pts. who cannot take PZA: INH, RFP x 9 months EMB or SM added initially unless resist. Risk 2x/w
29、k dosing can be given after 1-2 mo. if isolate sensitive b) Pregnancy: INH, RFP, EMB x 9 months (PZA avoided in USA),THE END,Thank you for your attention,All of the following are common challenges with the diagnosis and management of Tuberculosis in underserved regions EXCEPT,Mycobacteria cultures commonly not available Drug susceptibility testing usually not available High rates of HIV-MTB co-infection First-line TB treatment drugs usually not available Directly observed therapy (DOT) recommended but commonly not utilized,
