Download Fungal Infections in HIV

Fungal Infections in HIV-patients
Hail M. Al-Abdely, MD
Consultant, Infectious Diseases
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
Immunologic Status and Fungal Infections
CD4
Thrush
Dermatophyte
Seborrhea
Cryptococcosis
Histoplasmosis
Aspergillosis
Penicilliosis
Cutaneous Fungal Infections
• More common
• More extensive
• Relatively more difficult to treat
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
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
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
Esophageal Candidiasis
• Reported in 20% to 40% of all AIDS
patients.
• Characterized by pseudomembranes,
erosions and ulcers.
• Presentation is mainly with odynophagia
and dysphagia
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
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
90
80
70
60
50
40
30
20
10
0
Fever
Headache
Sweats Menigismus Visual
changes
MS
Dyspnoea
changes
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)
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)
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
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
Method of duplication
Budding
Fission
1-8 mcm
pleomorphic
elongated
Fission
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
Clinical Features:
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.