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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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CD4
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.
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