COHORT STUDY OF HIV POSITIVE AND HIV NEGATIVE TUBERCULOSIS in PENANG HOSPITAL: COMPARISON OF CLINICAL MANIFESTATIONS

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COHORT STUDY OF HIV POSITIVE AND HIV NEGATIVE TUBERCULOSIS in PENANG HOSPITAL: COMPARISON OF CLINICAL MANIFESTATIONS Ong CK 1, Tan WC 2, Leong KN 2, Abdul Razak M 1, Chow TS 2 1 Respiratory Unit, Penang Hospital 2 Department of Medicine, Penang Hospital

INTRODUCTION ( 1 ) The incidence of tuberculosis (TB) is currently increasing in HIV infected patients in many parts of the world. This has led to renewed interest in this ancient disease. The risk of developing TB after an infectious contact has been estimated to be 5-15%/year in HIV infected patients (compared to 5-10% during life time of non HIV infected patients). * * Raviglione M, Harries A et al. TB and HIV: Current status in African. AIDS 1997;11 (suppl. B).

INTRODUCTION ( 2 ) HIV induced immuno-suppression modifies the clinical presentation of TB. The treatment of TB is also more complex and difficult in HIV infected patients.

OBJECTIVES To look at the differences in clinical presentation of TB based on their HIV status. To look at the differences in clinical presentation of HIV and TB co-infection based on their CD4 counts.

METHODOLOGY ( 1 ) Retrospective Study All cases of adult active TB treated in the Respiratory Unit, Penang Hospital from January 2004 to December 2005. The information was obtained from patient s medical report, TB booklet, HIV clinic record and in-patient record (if they were admitted before). Demographic characteristics, clinical presentation, method of diagnosis, CD4 count and HIV status were recorded and analyzed.

METHODOLOGY ( 2 ) Diagnosis of TB were based on clinical impression and relevant investigations including a chest radiograph, sputum examination, tissue / blood culture for Mycobacterium Tuberculosis and biopsy when deemed necessary by the physician.

METHODOLOGY ( 3 ) HIV serological testing was performed using ELISA method and confirmed by Western Blot. Absolute CD4 lymphocyte numbers were quantified. HIV serological testing was done routinely for all newly diagnosed adult TB cases. Severely immuno-compromised patient was defined as CD4 count < 200 cell/mm 3.

METHODOLOGY ( 4 ) Inclusion criteria: Diagnosis of TB according to the WHO criteria and the Malaysian Clinical Practice Guideline for the control and management of TB Adult TB patient (>12 years old)

METHODOLOGY ( 5 ) Exclusion criteria: Diagnosis of active symptomatic bacterial infection (other than TB) or fungal or protozoal infection Statistical analysis: Using Chi-square test ( SPSS Version 13.0)

RESULTS Total of 820 patients treated for TB 103 patients are HIV infected patients ( 12.6% ) CD4 count ( mean ): 108.67

12 ( 24.5% ) 4 ( 21.1% ) 37 ( 75.5% ) 15 ( 78.9% ) NS NS

NS S S S

S NS NS

S NS NS

THE CLINICAL PICTURE OF TB DEPENDED ON THE STAGE OF HIV INFECTION & ASSOCIATED DEGREE OF IMMUNODEFICIENCY

DISCUSSION Tuberculosis has become of interest due to increased prevalence in many countries. The HIV pandemic has changed TB, from an endemic disease to worldwide epidemic.

TB-HIV COINFECTION In early HIV infection, the features are characteristic for post primary TB and resemble those seen in the pre-hiv era. More advanced immunodeficiency is usually associated with an increased frequency of disease resembling primary pulmonary TB and extra-pulmonary disease. Perronne C et al. Tuberculosis in patients infected with the HIV. Presse Med 1998. Jones BE et al. Relationship of the Manifestations of TB to CD4 counts in patients with human immunodeficiency virus infection. Am Rev Respir Dis 1993; 148: 1292-1297. L. Aaron et al. TB in HIV infected patients: A comprehensive review. Euro Society of Clin Microbio and Infect Dis 2004.

CLINICAL MANIFESTATION Prolonged insidious symptoms found in majority of patients consisting of weight loss, prolonged low grade fever and nocturnal sweat may delay the diagnosis. The classical picture of pulmonary TB is seen mainly in less immuno-compromised patients (CD4 count > 200 cells/mm 3 ). L. Aaron et al. TB in HIV infected patients: A comprehensive review. Euro Society of Clin Microbio and Infect Dis 2004.

CLINICAL MANIFESTATION All varieties of extra-pulmonary TB have been described in HIV infected patients. Isolated extra-pulmonary localizations are described in 53-63% of HIV associated TB cases. * ( In our series, only 18.4% are isolated extra-pulmonary ) Perronne C et al. Tuberculosis in patients infected with the HIV. Presse Med 1998. Jones BE et al. Relationship of the Manifestations of TB to CD4 counts in patients with human immunodeficiency virus infection. Am Rev Respir Dis 1993; 148: 1292-1297

MANTOUX TEST The contribution of skin test / Mantoux test for TB diagnosis depends on the immune status. During active TB, the Mantoux test is positive in 30% of HIV infected patients with a CD4 count < 200/mm 3 and in 50% of those with CD4 count > 200/mm *. ( In our series, it is 14.5% and 80.0% respectively ) Jones BE et al. Relationship of the Manifestations of TB to CD4 counts in patients with human immunodeficiency virus infection. Am Rev Respir Dis 1993; 148: 1292-1297

CHEST RADIOGRAPH Atypical features like lower lobe involvement with diffuse infiltrations are more commonly seen than cavitation. Cavitating lesions are rarely seen in patients with a CD4 count < 200/mm 3. Chest radiograph is normal in 8-20% despite the presence of smear positive sputum. * ( In our series, it is 11.7% ) Perlman DC et al. Variation of chest radiorgaphic patterns in pulmonary tuberculosis by degree of HIV related immunosuppression. CPCRA. Clin Infect Dis 1997. Perronne C et al. Tuberculosis in patients infected with the HIV. Presse Med 1998; 17: 1479-1483

CONCLUSION Worldwide incidence of TB is increasing, particularly in areas where HIV is prevalent. The CD4 count does not predict the occurrence of TB. Majority of HIV co-infected patients presented with prolonged, insidious and non specific symptoms like weight loss, fever and night sweats.

CONCLUSION HIV and TB co-infected patients with CD4 count 200 are more likely to have atypical chest radiographs. Mantoux test is not helpful to diagnose TB in those with late HIV disease. Therefore to diagnose TB in severely immunocompromised HIV patients, we need to have high index of suspicion.

THANK YOU