Fungal Infections in HIV-patients

1. Fungal Infections in HIV-patients Hail M. Al-Abdely, MD Consultant, Infectious Diseases

2. Fungal Infections in HIV-patients • Cutaneous • Seborrheic dermatitis • Onychomycosis • Skin dermatophyte infection • Muco-cutaneous • Candidiasis • Invasive • Cryptococcosis • Histoplasmosis • Candidiasis • Aspergillosis • Penicilliosis (Geographically restricted) • Coccidioidomycosis • Blastomycosis

3. Immunologic Status and Fungal Infections Thrush Dermatophyte CD4 Seborrhea Cryptococcosis Histoplasmosis Aspergillosis Penicilliosis

4. Cutaneous Fungal Infections • More common • More extensive • Relatively more difficult to treat

11. Systemic Treatment of Cutaneous Fungal Infections Fluconazole(Diflucan) Itraconazole(Sporanox) Terbinafine(Lamisil) Tinea corporis     and cruris 150 mg once a     week    3-4 weeks 200 mg qd     1-2 weeks 250 mg qd     2 weeks Tinea capitis 50 mg qd     3 weeks 3-5 mg/kg/day     4-6 weeks 125 mg qd     (3-6 mg/kg/day)     4 weeks Onychomycosis 150 mg once a     week    9 months 200 mg qd     Fingernails -6 weeks    Toenails - 12 weeks Pulse dosing     200 mg bid--    1 week on,    3 weeks off,    Toenails  3-4 months,    Fingernails     2-3 months 250 mg qd    Fingernails        6 weeks     Toenails         12 weeks Tinea pedis 150 mg once a week     3-4 weeks 400 mg qd 4 weeks 250 mg qd 6 weeks Tinea versicolor 400 mg single     dose 200 mg qd     5 or 7 days Studies ongoing

13. Oro-pharyngeal Candidiasis • 90% of HIV-patients develop OPC during their lifetime. • Candida appears as part of the mouth flora in more than 80% of HIV-positive patients. • Actual predisposing factors for progression from colonization to disease are not well characterized.

14. Treatment of OPC • Topical agents • Clotrimazole, nystatin, Ampho B • Systemic agents • Fluconazole • Itraconazole (Capsule, liquid) • Ampho B

15. Treatment of OPC • Systemic treatment • Fluconazole is the most common agent. • Faster action and less relapse than topical Rx. • Major problem with increasing resistance. • Higher dose. • Switch to other agents. • Strategies • Treat each episode • Continuous therapy

16. Esophageal Candidiasis • Reported in 20% to 40% of all AIDS patients. • Characterized by pseudomembranes, erosions and ulcers. • Presentation is mainly with odynophagia and dysphagia

18. Esophageal Candidiasis • Treatment • Commonly empiric therapy. • Endoscopy is indicated if the patient is not responding to antifungal therapy • Drugs • Fluconazole • Itraconazole (Capsule, liquid) • Ampho B

19. Candidiasis and HAART Since the advent of HAART, the incidence of new Candida infections has decreased by as much as 60% to 80%

20. Vaginal Candidiasis • Vulvo-vaginal candidiasis occurs in approximately 30% to 40% of HIV-infected women. • ? Candidiasis more common in women with HIV infection when other important risk factors for vaginal infection (sexual activity, racial and ethnic background). • HIV infection influences the severity and persistence of vulvo-vaginal Candida infection.

21. Cryptococcosis • Cryptococcus neoformansis an encapsulated yeast. • 5% of HIV-infected patients in the Western World develop disseminated cryptococcosis • CD4+ lymphocyte counts, less than 50 cells/mm3.

22. Cryptococcal Meningitis • Cryptococcosis typically presents as a subacute meningitis • Cryptococcal meningitis rarely presents as an obvious meningitis. • Initial symptoms are commonly more subtle and may just include fever and headache.

23. Symptoms of Cryptococcal Meningitis

25. Diagnosis of Cryptococcal Meningitis • Symptoms and Signs. • 70% of patients with cryptococcal meningitis have positive blood cultures • Serum cryptococcal antigen is a useful screening test. 1:8 is regarded as evidence of cryptococcal infection. • India ink (CSF): 50% sensitive, needs experience. • CSF cryptococcal antigen is rapid, sensitive and specific. • Histopathological stains • CSF culture.

26. Treatment of Cryptococcal Meningitis • Induction • amphotericin B, 0.7 mg/kg IV daily for 14 days or equivalent • consider 5-flucytosine (5-FC) 25 mg/kg PO q6 hours • measure opening pressure; consider means to reduce pressure if raised (>25 cms/water)

27. Treatment of Cryptococcal Meningitis Consolidation • fluconazole, 400 mg PO bid for 2 days, then daily for 8 weeks; or • itraconazole, 200 mg PO tid for 3 days, then bid for 8 weeks (appears to be slightly less active) • repeat lumbar puncture, with measurement of opening pressure, if patients remain symptomatic (especially persistent headache)

28. Treatment of Cryptococcal Meningitis Maintenance • fluconazole 200-400 mg daily • amphotericin B 1 mg/kg/week (less effective than fluconazole) • itraconazole 100-200 mg PO bid (less effective than fluconazole) • there is no value to routine measurement of serum cryptococcal antigen

29. Treatment of Cryptococcal Meningitis • Mild presentation • Fluconazole + 5-flucytosine • High dose fluconazole 800 mg QD • Close monitoring

30. Complications of Cryptococcal Meningitis • Acute mortality happens due to cerebral edema, which may be diagnosed by a raised opening pressure of the CSF. • Hydrocephalus

31. Dimorphic Fungi (Endemic Mycoses) • Histoplasmosis • Coccidioidomycosis • Penicilliosis marnefiei • Blastomycosis • Sporotrichosis

32. Histoplasmosis Coccidioidomycosis Penicilliosis

33. Histoplasmosis Coccidioidomycosis Penicilliosis Appearance of organism on biopsy 1-5 mcm round to oval 30-80 mcm round spherules containing 2-5 mcm endospores 1-8 mcm pleomorphic elongated Method of duplication Budding Fission Fission Clinical Features:   Fever 95% 95% 99%   Weight loss 90% 60% 75%   Anemia 70% 50% 75%   Pulmonary disease 50% 90% 50%   Lymphadenopathy 20% 10% 40-50%   Skin lesions 5-10% 5% 70%   Hepatosplenomegaly 25% 10-20% 50%   Meningitis <1% 10% Very rare Characteristics of the Endemic Mycoses

35. Aspergillosis • Tends to occur in the very late stages of HIV infection, typically in patients with a history of other AIDS-defining illnesses. • Two main presentations • respiratory tract disease • central nervous system infection

40. Conclusion • Fungal infections remain an important cause of morbidity and mortality in patients with HIV disease. • Epidemiology is changing with the advent of HAART. • High index of suspicion is important to make a diagnosis of some of the invasive mycoses. • Multiple opportunistic fungal infections can exist in the same patient on presentation.