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
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

9. Cutaneous candidiasis involving the moist skinfolds under the breasts
Cutaneous candidiasis involving the moist skinfolds under the breasts. The lesions are very red, and there are small red satellite lesions surrounding the main area of involvement. The typical location and the presence of satellite lesions make the gross image highly suggestive of cutaneous candidiasis. There is little tendency for deep tissue invasion with this type of lesion. (From Fitzpatrick et al.

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

12. Extensive pharyngeal candidiasis involving the soft palette and uvula of a patient with AIDS. Oral pharyngeal candidiasis can be a marker of T-cell immunosuppression. T cells are required to control candida growth on the mucosal surfaces. However, adequate neutrophil number and function are enough to prevent deep invasion, and there is surprisingly little tendency to develop disseminated candidiasis in patients who are T-cell deficient. (From Fitzpatrick et al.

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 Systemic agents
Clotrimazole, nystatin, Ampho B
Systemic agents
Fluconazole
Itraconazole (Capsule, liquid)
Ampho B

15. Treatment of OPC Systemic treatment Strategies
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 neoformans is 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 mg daily
amphotericin B 1 mg/kg/week (less effective than fluconazole)
itraconazole 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. Characteristics of the Endemic Mycoses
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
Clinical Features:
  Fever
95%
99%
  Weight loss
90%
60%
75%
  Anemia
70%
50%
  Pulmonary disease
  Lymphadenopathy
20%
10%
40-50%
  Skin lesions
5-10% 5%
  Hepatosplenomegaly
25%
10-20%
  Meningitis
<1%
Very rare

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.