Hail M. Al-Abdely, MDHail M. Al-Abdely, MD

Consultant, Infectious DiseasesConsultant, Infectious Diseases

Fungal Infections in HIV-patients

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

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CryptococcosisHistoplasmosisAspergillosisPenicilliosis

ThrushDermatophyte

Seborrhea

Immunologic Status and Fungal InfectionsImmunologic Status and Fungal Infections

Cutaneous Fungal Infections

• More common

• More extensive

• Relatively more difficult to treat

   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

Systemic Treatment of Cutaneous Fungal Infections

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.

Treatment of OPC

• Topical agents – Clotrimazole, nystatin, Ampho B

• Systemic agents– Fluconazole– Itraconazole (Capsule, liquid)– Ampho B

• 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

Treatment of OPC

Esophageal Candidiasis

• Reported in 20% to 40% of all AIDS patients.

• Characterized by pseudomembranes, erosions and ulcers.

• Presentation is mainly with odynophagia and dysphagia

• Treatment– Commonly empiric therapy.– Endoscopy is indicated if the patient is not

responding to antifungal therapy– Drugs

• Fluconazole

• Itraconazole (Capsule, liquid)

• Ampho B

Esophageal Candidiasis

Candidiasis and HAART

Since the advent of HAART, the incidence of new Candida infections has decreased by

as much as 60% to 80%

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.

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.

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.

Symptoms of Cryptococcal Meningitis

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Fever Headache Sweats Menigismus Visualchanges

MSchanges

Dyspnoea

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.

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)

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)

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

Treatment of Cryptococcal Meningitis

• Mild presentation– Fluconazole + 5-flucytosine– High dose fluconazole 800 mg QD– Close monitoring

Treatment of Cryptococcal Meningitis

Complications of Cryptococcal Meningitis

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

• Hydrocephalus

Dimorphic Fungi (Endemic Mycoses)

• Histoplasmosis

• Coccidioidomycosis

• Penicilliosis marnefiei

• Blastomycosis

• Sporotrichosis

Histoplasmosis Coccidioidomycosis Penicilliosis

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 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

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

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.