Pneumocystis jiroveci pneumonia and other pulmonary infections in TB smearnegative HIVpositive patients with atypical chest xray in Ethiopia
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Pneumocystis jiroveci pneumonia and other pulmonary opportunistic infections in TB smear- negative HIV-positive patients with atypical chest x-ray in Ethiopia Background PCP is reportedly rare in sub-Saharan Africa (sSA) A rising prevalence noted recently - Before 1994(11 studies); median prev. 5% (0-22%) - 1995- 2001(12 studies); median prev. 21% (0-39%) - Children; median prev.(13 studies) : 33% (14-67%) - Ethiopia 1996/97 prevalence= 10.9% by IF & 30.3% by n-PCR PCP guised as smear –ve TB ( Uganda; 38.6%, Malawi (5%)
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2/3 of global AIDS burden in sSA PCP Prophylaxis & HAART not widely used in sSA Is a PCP epidemic likely to occur in Africa? B) Objective of the study To determine the relative prevalence of PCP & other pulmonary OIs. To evaluate the use of a simple and rapid diagnostic method, Toluidine Blue O stain for the diagnosis of PCP C) Methods i) Patient recruitment scheme (Fig.1)
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ii) Physician DX documented & CXR read independently by two radiologists iii) Criteria for diagnosis PTB: A patient with suggestive clinical symptoms and a positive sputum or BAL culture for M. tuberculosis. PCP: Isolation of P. jiroveci from sputum or BAL by immunoflorescence staining. Bacterial infection: The presence of excessive amount of purulent secretion coming out from the tracheo-bronchial tree during bronchoscopy and the BAL specimen grew bacteria while it was negative for M.TB, PJ or fungal pathogens.
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Non- specific interstitial pneumonitis (NIP): The findings of bilateral diffuse interstitial infiltrate with indolent course that failed to clear with treatment for bacterial infection or PCP and BAL is negative for TB, PCP and fungi. Pulmonary Kaposi Sarcoma (PKS) : The presence of typical macular, violaceous lesions observed over the tracheo-bronchial tree during bronchoscopy. Clinical PCP: A patient presenting with clinical symptoms and CXR typical for PCP and responding to high dose co-trimoxazole treatment adequately in spite of a negative study for PJ.
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D) Results i) Screening protocol for pt. enrollment (Fig. 2) ii) Patient characteristics - 131 consecutive pts. enrolled - 70% outpatients - M:F ratio 55:76 - Median age = 35 yrs - 75% either married, divorced or widowed - 85 of the 131(65%) could produce sputum for MTB (only 77 adequate for PJ stain) - 120 underwent bronchoscopy ( two inadvertently ) excluding 13 sputum +ve PJ
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iii) Final diagnoses - 148 diagnoses in 131 pts (17 double infection) - Bacterial infections = 44 (33.6%) - PCP = 39 (29.8%) - Pulmonary TB = 31 (23.7%) - PKS and NIP in 4 patients each - Pulmonary strongloides in one patient - Definitive diagnosis= 107 (81.7%) pts - Presumptive Dx in 24 pts of whom 17 were suspected PCP a) PCP - Dx from ES in 14 and from BAL in 25 - 21 (53.8%) on Rx for PCP for < 7 days - Median duration of illness (in wks)= 7.2
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- Sensitivity physicians Dx = 61.5% - Sensitivity CXR= 90%; specificity= 54.4% b) Tuberculosis - Sputum culture +ve in 13 of 85 (15.5%) - BAL culture +ve in 26 (22%) - 1/3 treated for TB in the past, relapse ? c) Bacterial infections - Median duration of illness (in wks)= 13.23 - 272 bacterial isolates in 116 sample - Median nr. of isolates = 2 (range 2-5) - 24 different type of bacteria (Table 1) - Median nr. & pattern of isolates similar in the 3 diseases, - Sensitivity, physicians & CXR Dx, 16.2% & 18.6%
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- Sensitivity of physician’s and CXR Dx, 26.9% & 42.3 % respectively. PPV of CXR= 42.3% - 50% of the CXR read as PCP, hence delay in Dx. d) Others: Hyperactive airway disease observed in 31 (23.8%) pts. Vs 1-3.6 % for the general population e) Clinical Predictors of diagnosis -Univariate analysis: PCP: Absent chest pain; severe SOB; ? 02 sat.; ?ESR; ? CD4 count; typical CXR TB: Hemoptysis Bacterial infections: ?Duration of illness; purulent sputum
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-Multivariate analysis, predictors of diagnosis - Typical CXR & ?CD4 count for PCP - purulent sputum for bacterial infections g) CXR findings - 4 out of 131 (3.1%) had normal CXRs - PPV of CXR for PCP, TB and bacterial infections was: 45.6%, 42.3% & 33.3% - Discordant reading in 25 (19.5%) cases - Most common discordance between TB & PCP - Level of agreement (79.3%, Kappa= 0.792, +/- SE of Kappa=0.095), rated as very good
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Clinical & lab findings, PCP, TB &bacterial infections
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Multivariate regression analysis for independent predictors of PCP, TB & bacterial infections
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E) Discussion/ Conclusion - PCP is an important Ddx of smear –ve, HIV +ve pts with atypical CXR -A rising prevalence has been observed in Ethiopia (10.3% by IF, 1996/97 vs 30%, 2005/06) - Similar trend in other sSA (eg Kenya, Uganda etc) - Is PCP a previously undiagnosed or newly emerging pathogen in Africa ?
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- PCP is an important Ddx of smear –ve TB ( 50% of smear –ve, culture proven TB cases were considered as PCP) - PCP should be included in the diagnostic algorithm of smear –ve TB. - Difficult to construct a clinical PCP diagnostic algorithm using clinical symptoms & CXR a) Clinical predictors: Not enough to discriminate between the various diagnoses b) Frequent double infection c) Low PPV both by physicians and radiologists
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- Therefore, there is a need to make definite Dx of PCP in sub-Saharan Africa -Chronic bacterial infection is a neglected but common disorder. - Both physicians and radiologists rated very badly in the DX of bacterial infection (<20%) -Purulent sputum is an independent predictor - BAL culture not helpful to make an etiologic Dx.
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- Large (>50%) of TB cases diagnosed as PCP; delay in DX; increased morbidity & excess mortality - This calls for lowering the threshold for the DX of TB in smear –ve, HIV +ve patients. - Kaposi and NIP are not major problems in Ethiopia - No fungal pulmonary infection detected - Significant hyperactive airway disease related to HIV
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Acknowledgements: This study was a collaborative work between: The Department of Internal Medicine, A Ababa University, Black Lion University Hospital Division of Infectious Diseases, Dept. of Internal Medicine, Huddinge University Hospital, Karolinska Institute, Sweden Dept. of Radiology at AAU Dept. of Microbiology at AAU Swedish Institute for Infectious Diseases Control(SMI) Armauer Hansen Research Institute in A Ababa
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The study was financially supported by SIDA/SAREC, Project SWE – 2000 - 157
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