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Tuberculosis in The Age of Hiv
Tuberculosis in The Age of Hiv
Tuberculosis in The Age of Hiv
THE PROBLEM
Global epidemic of HIV infection. HIV- infected persons highly susceptible to M. tuberculosis disease. Impact of HIV epidemic and TB greatest in the developing world. 33% HIV infected population co-infected with TB. TB - the most common opportunistic lung infection.
Caribbean
2000
168
160
140
120
Number of Cases
100 78 61 60 40 21 20 2 1984 (20) 1985 1986 1987 1988 1989 1990 1991 1992 9 24 15 78
90
80
40
1993
1994
1995
1996
1997
1998
Years
500 Number of Cases 400 300 198 166 115 100 8 13 83 52 164 298 249 302 264 399
468 408
459
200
1983 1984 1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 (100) Years
892
99
1982 1983 1984 1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 Years
CO-INFECTION RATES
Jamaica
YEAR 1994 1995 1996 1997 1998 1999 2000 No. Tb Cases 109 109 121 118 121 108 124 No Tb/HIV 5 7 14 14 10 8 18 Percent co infected 4.6% 6.4% 11.6% 11.9% 8.3% 7.4% 14.5%
CO-INFECTION RATES
T / H C -ine t dC s s Ja a a1 9 -2 0 b IV o f c e a e , mic 9 1 0 0
1. 0 60 % 1. 0 40 % 1. 0 20 % 1. 0 00 % 80 % .0 60 % .0 40 % .0 20 % .0 00 % .0
19 91 19 92 19 93 19 94 19 95 19 96 19 97 19 98 19 99 20 00
T /HV b I
PATHOGENESIS OF CO-INFECTION
HIV-infected persons are at risk for primary or reactivated TB, and for second episodes of TB. Reduced T1 response. CD 4+ lymphocytes unable to produce alpha- interferon. Alpha-interferon central to anti- mycobacterial immune defenses.
PATHOGENESIS OF CO-INFECTION
Presence of TB up-regulates retroviral replication. TB infection produces proinflammatory cytokines. Risk of death 2x greater in HIVinfected patients with TB. Death due to progression of HIV and not TB.
CLINICAL PRESENTATION
Dependent on degree of immunosuppression. Presentation varied. Extra-pulmonary TB, particularly lymph node involvement more common.
Diagnosis
History- Malaise, weight loss, fever, cough, haemoptysis Physical Examination Laboratory Examinations AFB smear, lymph node biopsy, BAL, pleural biopsy, cultures Chest X-ray findings variable ? Mantoux Test ? Rapid diagnostic tests- identifies TB RNA or DNA
RULobe abscess
Six months vs. Nine months Clinical or bacteriological delayed response- Longer therapy. Lack of adherence to therapy most important impediment to cure. Higher risk of MDRTb Greater risk of prolonged disease. Strong public health services (DOT) improve outcome.
TREATMENT OF TUBERCULOSIS
First line drugs- Rifampin, Isoniazid, Pyrazinamide, Ethambutol, Streptomycin. Rifampin- most important and most potent. Second line drugs- Quinolones, Amikacin, Capreomycin.
ANTI-RETROVIRAL THERAPY
HAART dramatic improvement in prognosis for HIV- infected patients. Drug interactions complicate the management of tuberculosis. Interaction is mainly with the Rifamycins.
Rifampicin is the most potent inducer CYp450 Rifabutin is the least potent inducer and may be substituted for rifampicin. Clinical trials have demonstrated comparable safety and efficacy. The dose of rifabutin should be reduced from 300 to 150 mg daily in pts. on Protease Inhibitors.
CDC. Report of the NIH panel to define principles of therapy of HIV infection and guidelines for the use of antiretroviral agents in HIV-infected adults and adolescents. MMWR 1998; 48 ( No. RR-5): 1 -63
CONTROVERSIES
? Continuation of anti-retroviral therapy during Anti-TB therapy. ? Anti-TB regimens not including a rifamycin. ? When to initiate anti-retroviral therapy in HIV-infected TB patient. ? Risk of paradoxical reactions and glucocorticoid therapy. ? Malabsorption of anti-TB meds.
PARADOXICAL REACTIONS
q
Up to 1/3 of co-infected patients on anti-Tb meds will experience paradoxical worsening when antiretroviral therapy is introduced. The clinical manifestation is usually fever, intrathoracic and cervical lymphadenopathy, pleural effusions and/or skin lesions. Usually occurs within 15 days of initiation of therapy.
Paradoxical worsening of Tb following antiretroviral therapy in pts with AIDS Am. J Respir Crit Care Med 1998; Nariita M et al Smith H. Paradoxical responses during the chemotherapy of tuberculosis. J. Infect Dis 1987; 15: 1-3
PARADOXICAL REACTIONS
q
This appears to be associated with a marked drop in HIV viral load even though the peripheral CD4+ remains abnormally reduced Paradoxical reactions have been attributed to strengthening of the hosts delayed hypersensitivity response, a decrease in suppressor mechanisms and / or an increased exposure to mycobacterial antigens following bactericidal TB chemotherapy
CHEMOPROPHYLAXIS FOR TB
Need to exclude active disease. Recommended for recent close contact with potentially infectious persons with TB. ? Positive Mantoux test and need for prophylaxis. Isoniazid for nine months OR Rifampin/ Rifabutin & Pyrazinamide for two months.
THE FUTURE
Decline in the number of TB cases in persons with HIV due to better availability of ARV. Development of new anti-Tb and ARV with fewer drug interactions essential to reduce morbidity and mortality. Strengthened Public Health Services
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