Overview of Opportunistic Infections in HIV/AIDS

1. Overview of Opportunistic Infections in HIV/AIDS HAIVN Harvard Medical School AIDS Initiative in Vietnam

2. Learning Objectives By the end of this session, participants should be able to: • Explain the relationship between CD4 count and incidence of specific opportunistic infections (OIs) • Describe the most common OIs in Vietnam including: • clinical presentation • diagnosis • national treatment recommendations

3. What is an Opportunistic Infection (OI)? • An infection caused by pathogens that usually do not cause disease in a host with a healthy immune system • A compromised immune system presents an "opportunity" for the pathogen to infect

4. What is the Relationship Between CD4 Count and OIs? • The lower a person’s CD4 count is, the more vulnerable he/she is to opportunistic infections (OIs) • Different infections can occur based on how weak a person’s immune system is • The level of CD4 count determines the OIs for which a person is at risk

5. Sample OIs per CD4 Count

6. Key Principles of OI Diagnosis and Treatment • Accurate diagnose of OIs require consideration of: • Clinical features • Severity of immunosuppression • Results of specific lab tests • Patients often have multiple OIs at the same time • Drug-drug interactions are an important consideration in the management of OIs

7. Clinical Presentation, Diagnosis and Treatment of Major OIsin Vietnam

8. What are Common OIs in Vietnam? • Oral Candidiasis (Thrush) • Tuberculosis • Penicilliosis • Cryptococcal Meningitis • PCP • Cerebral Toxoplasmosis • Cytomegalovirus (CMV) Retinitis • Mycobacterium Avium Complex (MAC) • Cryptosporidiosis • Isosporiasis and Cyclosporiasis

9. Oral Candidiasis (Thrush) • Most patients have no symptoms • Shows as white plaques on palate, gums • Treatment: • Fluconazole 150mg/day for 7 days • Ketoconazole 200mg bid for 7 days White plaques on palates, removable by tongue blades

10. Candida Esophagitis Patients complain of: • pain in throat or chest when swallowing • food getting “stuck”

11. Tuberculosis (1) • TB is the most common OI in Vietnam and the most common cause of death among HIV patients • Clinical symptoms of pulmonary TB include fever, cough, night sweats, weight loss, and bloody sputum • Extrapulmonary TB is more common in HIV+ compared to HIV- patients

12. Tuberculosis (2) Right upper lobe infiltrate Diagnosis: • Clinical symptoms • CXR • Sputum AFB smear • Bronchoscopy where available • Tissue biopsy (lymph nodes)

13. Pneumocystis jiroveciPneumonia (PCP) (1) • Clinical manifestations include: • gradual onset of shortness of breath • dry cough • fever • Lung sounds may be clear or have faint crackles • Hypoxia is common • Elevation of LDH is common but nonspecific • CD4 <200 (though occasionally higher)

14. Pneumocystis jiroveciPneumonia (PCP) (2) • Typical CXR • bilateral diffuse infiltrations • Atypical CXR • normal result • blebs and cysts • lobar infiltrates • Suggestive CXR • pneumothorax

15. PCP Diagnosis (1) • Diagnosis can be made clinically • Empiric treatment should be started if the diagnosis is suspected • Definitive diagnosis is made by sputum smear and stain Fluorescent stain

16. PCP Treatment National Treatment Protocol

17. Case Study: Duc (1) • Duc, a 30 year-old HIV positive man, presents to OPC with cough of 3 weeks duration • Scanty whitish sputum • Low grade fever • Developed shortness of breath one week ago • On examination he was in respiratory distress with RR of 40/min and cyanosis • What are the likely causes? • What important tests would you request?

18. Case Study: Duc (2) Results of tests: • Sputum AFB: negative 3 times • CXR: bilateral infiltrates • CD4: 110/mm3

19. Penicilliosis (1) • Causative agent Penicillium marneffei • First isolated in 1956 in Vietnam from the bamboo rat • Endemic in southeast Asia and southern China • First case reported in an AIDS patient was in Vietnam in 1996 • Majority of cases occur in patients with CD4 cell counts < 100 Source: Hien TV et al. CID 2001;32:e78-80.

20. Penicilliosis (2) • Most common signs and/or symptoms include: • Fever • Weight loss • Skin lesions • Lymphadenopathy • Hepatomegaly • Splenomegaly • Anemia • Elevated AST, ALT

21. Typical Skin Lesions of P. Marneffei Cutaneous papules with central necrotic umbilication. May be confused with molluscum contagiosum or disseminated cryptoccocus.

22. Penicilliosis- Diagnosis Direct microbiological exam Culture • P. marneffei cultures (blood or skin lesions) produce a distinct red diffusible pigment Wright stain of skin lesions

23. Penicilliosis- Treatment National Treatment Protocol

24. Cryptococcal Meningitis (1) Clinical manifestations: • Headache, fever, nuchal rigidity, fatigue, mental disorders • Course can be chronic (months) • Meningeal signs may be absent in advanced AIDS cases • CD4<100

25. Cryptococcal Meningitis (2) • Diagnosis of CM is done by examining cerebral spinal fluid (CSF) after performing a lumbar puncture • Opening pressure • CSF parameters (cell count, protein, glucose) • Microbiology • India Ink stain • Cryptococcal antigen test • CSF culture

26. Cryptococcal Meningitis - Treatment

27. Cerebral Toxoplasmosis • Seen in patients with CD4<100 • Clinical manifestations: • Fever • Headache • Confusion • Motor weakness • Focal neurological deficit • Seizures, stupor, coma

28. Cerebral Toxoplasmosis – Diagnosis (1) • MRI of cerebral toxoplasmosis showing 2 ring enhancing lesions – “lighting up” with intravenous contrast

29. Cerebral Toxoplasmosis – Diagnosis (2) • Empiric treatment with good clinical response • (+/-) improvement of brain imaging • Positive blood serology (IgG) to T. gondii • Indicates prior infection • Negative serology makes cerebral toxoplasmosis less likely • Brain or tissue biopsy • crescent/banana shaped tachyzoites

30. Cerebral Toxoplasmosis: Treatment

31. Case Study: Huong • Huong, a 31 year-old HIV-positive woman from Hanoi, presents with weakness of left upper and lower extremities for 5 days duration • Complains of fever, severe headache and vomiting for last 2 weeks • Not taking any medication • Examination revealed a confused woman with weakness of left extremities but no meningeal signs • What is Huong’s differential diagnosis?

32. Mycobacterium Avium Complex (MAC) • Prevalence unknown in Vietnam • 3% of cohort of AIDS patients in Hanoi • Manifestations • CD4 < 50 • Fever • Weight loss • Lymphadenopathy • Hepatosplenomegaly • Anemia • Diagnosis • Blood culture • Bone marrow and lymph node biopsies with culture • Treatment • Clarithromycin or azithromycin PLUS ethambutol

33. Cytomegalovirus (CMV) Retinitis Presentation: • CD4 < 50 • blurred vision • blind spots “floaters” • blindness • painless condition Treatment: • Ganciclovirintravitreal* or intravenous injections • ART • * Ganciclovir intravitreal injections are available at the national level in both north and south Vietnam

34. Cryptosporidiosis (1) • Caused by infection with C. parvum • generally infects small bowel mucosa • Transmission • ingestion of the cysts (usually in water contaminated with feces) • Can affect patients at any CD4 count • CD4 < 100 are at highest risk for most severe infection

35. Cryptosporidiosis (2) Clinical presentation • acute or subacute • non-bloody, watery diarrhea • nausea and/or vomiting • lower abdominal cramps • fever can occur Diagnosis • Modified AFB stain Treatment • Supportive • ART to raise CD4 count

36. Isosporiasis and Cyclosporiasis • Transmitted by ingestion of contaminated food and water • Clinical presentation • chronic voluminous watery diarrhea • abdominal cramps, nausea/vomiting • weight loss • Treatment • TMP-SMX 2 DS tablets twice or three times daily for 2 – 4 weeks • ART to raise CD4 counts

37. Case Study • A 32-year-old IDU comes to the clinic complaining of persistent diarrhea that started five months earlier • You do a CD4 count and stool exam • His CD4=70 • His stool reveals cryptosporidium • How would you classify his clinical stage? • With a CD4 count of 70, what other OIs is he at risk for?

38. Key Points • An OI is caused by pathogens that usually do not cause disease in a healthy host • Knowing a PLHIV’s CD4 count can help clinician better diagnose an OI • Accurate diagnose of OIs require consideration of: • Clinical features • Severity of immunosuppression • Results of specific lab tests

39. Thank you! Questions?