1. HIV Associated Opportunistic Infections in Ethiopia Daniel Fekade MD, MSc Faculty of Medicine, Addis Ababa University

2. HIV ASSOCIATED OPPORTUNISTIC INFECTIONS Opportunistic infections are major causes of morbidity & mortality among HIV infected patients Many of the common opportunistic infections are both preventable/treatable However, inadequate infrastructures make it difficult to implement prevention/treatment programs in many developing countries

3. Major diagnostic categories among 237 HIV infected medical inpatients Tikur Anbessa Hospital, Addis Ababa, Jan-Dec, 2000. Diagnoses, (Number of patients), Percent of total Oropharyngeal candidiasis (136), 57.4% Tuberculosis (131), 55.3% CNS mass lesion (74), 31.2% Sepsis (59), 24.9%

4. Major diagnostic categories of HIV infected patients (contd.) Pneumocystis pneumonia (34) 14.3% Bacterial pneumonia (22) 9.3% Kaposi's sarcoma (20) 8.4%

5. Major diagnostic categories of HIV infected patients (contd.) AIDS dementia (14) 5.9% Cryptococcal meningitis (14) 5.9% Peripheral neuropathy (11) 4.6% Myelopathy (11) 4.6% Lymphoma (7) 3.0 % Others* (82) 34.6%

6. Causes of hospital death among HIV positive medical inpatients. In hospital mortality rate (70) 30% Cause of death (Number of patients) Percent of total (%) Tuberculosis (41) 56.2% Sepsis (41) 56.2% CNS mass lesion (26) 35.6%

7. Causes of hospital death among HIV medical inpatients (contd.) Bacterial pneumonia (10) 13.7% Pneumocystis pneumonia (8) 11% Cryptococcal meningitis (6) 8% Others*(16) 21.9% Unknown (4) 5.5%

8. Management of HIV- associated tuberculosis Tuberculosis is the leading opportunistic infection in persons infected with HIV in developing countries. HIV seroprevalence among tuberculosis patients in Ethiopia estimated to be 44% (MOH, unpublished report 1994) 5%-10% of HIV seropositive patients develop active disease annually (cf. 5% cumulative lifelong risk in seronegatives).

9. Clinical presentation of tuberculosis among 131 HIV infected patients Prevalence of TBc among HIV medical inpatients, (131/237) 55.3% Disseminated TBc (66/131) 50.4% Pulmonary TB (37/131) 27% Smear positive (8/37) 21.8% Smear negative(29/37) 78.4 Meningitis (11) 8.4%

10. Clinical presentation of tuberculosis among 131 HIV infected patients (contd.) Lymphnode (5) 3.8% Pleural(5) 3.8% Tuberculoma (4) 3.1% Spondylitis (3) 2.3%

11. Problems in the management of HIV associated tuberculosis: High incidence of adverse drug reactions (18% vs. 5%) Atypical presentation/extra pulmonary disease Resistance to any one or more of the first line anti-TB drugs in Ethiopia, 15% - 33% MDR TB, resistance to both rifampicin and INH, among previously untreated patients 5%

12. Preventive therapy against tuberculosis in people living with HIV Progression to active disease in persons latently infected, 3.5-9.7 per 100 person years; relative risk – 20 TB prophylaxis increases survival of HIV infected persons at risk of TB e.g. persons residing in endemic regions. INH preventive therapy for a year costs US$ 5.15 – affordable However, inadequate infrastructures make it difficult to be practicable

13. HIV Associated Cryptococcal Meningitis Clinical presentation: Occurs in persons with advanced immunodeficiency, CD4 <100/μl Subtle clinical presentation, headache, fever, malaise; absent meningeal signs Altered sensorium in 25%, and focal signs 5%

14. HIV Associated Cryptococcal Meningitis Diagnosis CSF, Indian ink/culture; yield about 75% Cryptococcal antigen assays, CSF/serum Blood culture

15. HIV Associated Cryptococcal Meningitis Treatment Induction: Amphotericine B; 0.7-1mg/kg/day IV, With/without flu cytosine 100mg/kg/day PO for 14 days, Consolidation: fluconazole 400mg/day for 8- 10 weeks, Maintenance: fluconazole 200mg/day, lifelong.

16. Management of Toxoplasmosis in Patients with HIV Infection Epidemiology: Toxoplasma gondii is a zoonotic infection Cats are the definitive hosts, and excrete T gondii oocysts in their feces T gondii cysts are found in undercooked meat Prevalence of latent T gondii infection is high in Ethiopia; 85% seropositive for anti- toxoplasma antibodies.

17. Toxoplasmosis, clinical presentation: Typical presentation is an altered mental state, seizures, weakness, and cranial nerve abnormalities Onset is usually subacute, nearly 90% of cases develop focal neurologic signs Commonly affected areas, basal ganglia, brain stem and cerebellum Extracranial sites may occur, retina, myocardium, and lungs

18. Diagnosis of toxoplasmosis : Neuro- radiologic imaging: Contrast enhanced CT, hypodense multiple lesions with ring-enhancement after IV contrast Solitary lesions present with diagnostic difficulties Therapeutic trial, clinical / radiological response in two to three weeks

19. Toxoplasmosis, diagnosis (contd.) Serologic assays: A negative Toxoplasma antibody test makes the diagnosis of toxoplasmosis less likely. Histologic diagnosis: Brain biopsy; Wright-Giemsa, fluorescent antibody staining

20. Management of toxoplasma encephalitis Two major regimens: Pyrimethamine plus sulfadiazine OR Pyrimethamine plus clindamycin both with folinic acid duration of treatment six weeks Suppressive/maintenance treatment continued for life

21. Management of toxoplasmosis (contd.) High rates of adverse reactions with pyrimethamine-sulfadiazine Experimental therapies: azithromycin, clarithromycin, trimetrexate, doxycycline, atovaquoune Corticosteroids may be used in patients with cerebral edema and increased intracranial pressure.

22. Preventive therapies for toxoplasmosis: Indications CD4+ count < 100 cells/μl Positive T gondii serology Regimens TMP-SMX two tablets per day (single strength) Alternative regimens Dapsone 50mg daily, plus pyrimethamine 50 mg po weekly

23. The management Pneumocystis pneumonia in patients with HIV infection Epidemiology: PCP is the most frequent opportunistic infection in industrialized countries, but less frequent in Africa. Infection transmitted from human to human, or from environmental reservoirs to humans. Antibody studies suggest that most humans are infected early in life Infection transient, or long lived with periods of latency?

24. Pneumocystis pneumonia, Clinical presentation: Onset, subacute Dyspnea, non-productive cough, fever Chest X-rays; diffuse bilateral interstitial infiltrates Numerous examples atypical radiographic presentations e.g. unilateral infiltrates, cavities, effusions Hypoxemia, and elevated serum LDH

25. Pneumocystis pneumonia, diagnosis : Demonstration of the organism in bronchoalveolar lavage (BAL), sensitivity 95- 100% Induced sputum, sensitivity 30-90% Pulmonary biopsy, sensitivity 90-95%, reserved for unusual cases Staining; Wright-Giemsa, methenamine silver, direct immunoflourescence

26. Treatment of pneumocystis pneumonia: TMP-SMX is the gold standard for the treatment of PCP It can be given either IV, or PO Usual dose, 15mg/kg/day (based on the trimethoprim component) in 3-4 divided doses for 14 days (typical oral dosage 2 DS tid). Adverse drug reactions in 25-50%, primarily skin rash +/- fever Patients with moderate/severe disease should receive corticosteroids

27. Pneumocystis pneumonia, alternative regimens: Clindamycin 600 mg IV q8h or 300-450 mg PO q6h + primaquine 30 mg base/day, 21 days Pentamidine 4 mg/kg/day IV, 21 days (usually reseved for severe cases) Atovaquone 750 mg suspension PO with bid, 21 days

28. Pneumocystis pneumonia, preventive therapies Prevention is strongly recommended for HIV infected person with significant immune deficiency: Indications: CD4+ count < 200/μl Prior episode of PCP HIV associated thrush Unexplained fever

29. Preventive therapy, pneumocytis pneumnia Regimens: TMP-SMX two tablets/day (single strength) TMP-SMX two tablets three times per week Alternative regimens: Dapsone 100 mg PO daily Dapsone 50 mg PO daily, plus pyrimethamine 50 mg PO weekly, plus leucovirin25 mg Po weekly Aerosolized pentamidine 300 mg monthly via nebulizer Atovaqoune 1500 mg daily