Transcript MAC

AIDS and related syndrome
Clinical manifestation and
staging of HIV infection
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Acute HIV infection or primary HIV
infection
Asymptomatic stage or clinical
latency
Early symptomatic stage or AIDSrelated complex (ARC)
Advanced HIV disease or AIDS
CD4 levels and common OIs
CD4 levels and common OIs
Natural Course of HIV Infection and Common Complications
1000
VL
CD4+ cell Count
900
CD4+ T cells
800
Relative level of
Plasma HIV-RNA
700
TB
600
500
400
300
HZV
Acute HIV
infection
syndrome
Asymptomatic
OHL
200
PPE OC PCP
100
0
TB
CM
CMV, MAC
0 1 2 3 4 5
Months
1
2
3
4
5
6
Years After HIV Infection
7
8
9
10
11
Advanced HIV disease or
AIDS
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CD4+ T cell < 200 cells/mm3
Common AIDS-defining illness in HIV – infected
Thai adults
– Candidiasis
– Cryptococcosis
– Penicillosis marneffei
– Histoplasmosis
– Cytomegalovirus
– Mycobacterium avium complex
– Toxoplasmosis
Candidiasis
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Candida infection in AIDS is almost
exclusively mucosal
Oropharyngeal candidiasis occurs in
74% of HIV-infected patients
1/3 is recurrent and more severe as
immunodeficiency advances
Esophageal involvement is reported in
20 to 40% of all AIDS patients
Clinical features
of oral candidiasis
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Most patients are symptomatic and
may complain of some oral discomfort
4 forms of oral lesions:
pseudomembranous, erythematous (or
atrophic), hypertrophic, and angular
cheilitis
Pseudomembranous
(thrush) type
Erythematous
(atrophic) type
Hypertrophic type
Clinical features
of vaginal candidiasis
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Most patients present with vaginal
itching, burning or pain and vaginal
discharge
Examination of the vaginal cavity
reveals thrush, identical to that seen
in the oropharynx
Clinical features
of esophageal candidiasis
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Typical symptom: dysphagia or odynophagia
Esophageal lesions: pseudomembranes,
erosions, and ulcers
Combination of oral candidiasis and
esophageal symptoms is both specific and
sensitive in predicting esophageal
involvement
Clinical features
of esophageal candidiasis
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Patients who present in this manner
can be treated empirically with
antifungal therapy
Endoscopy is reserved in those
patients who fail to respond or to
evaluate for the presence of other
diagnoses: HSV or CMV esophagitis,
idiopathic ulceration
Diagnosis of candidiasis
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Fungal cultures are rarely required
for diagnosis and can cause confusion,
since many patients are colonized
with Candida
Scraping of a lesion will show
characteristic spherical budding
yeasts and pseudohyphae (KOH
preparation or gram stain)
Diagnosis of candidiasis
Therapeutic options for
oral candidiasis
Treatment of vulvovaginal
candidiasis
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Initial episodes are managed readily
with topical therapy (clotrimazole,
miconazole, or butoconazole)
Systemic therapy is rarely needed
for uncomplicated cases
Fluconazole single dose of 150 mg
orally is a popular alternative
Candida esophagitis
Treatment of acute infection
• Drug(s) of first choice: Fluconazole 200 up to 400
mg/d x 2-3 wk
• Alternatives: Ketoconazole 200-400 mg bid x 2-3 wk or
Itraconazole 100-200 mg bid or Amphotericin B 0.3-0.5
mg/kg/d IV +/- 5-FC 100 mg/kg/d x 5-7 days
Suppressive therapy
• Drug(s) of first choice: Fluconazole 100-200 mg/d
• Alternatives: Ketoconazole 200 mg/d or Itraconazole
200 mg/d or Nystatin or clotrimazole
Cryptococcosis :
Cryptococcal meningitis
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Virtually all HIV-associated infection
is caused by C. neoformans var.
neoformans (serotypes A and D)
Most cases are seen in patients with
CD4 <50 cells/mm3
acute primary infection or
reactivation of previously dormant
disease
Clinical features of cryptococcosis
Diagnosis of cryptococcosis
Wright’s stain
Acid-fast stain
Diagnosis of cryptococcosis
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CSF: mildly elevated protein, normal
or slightly low glucose, a few
lymphocytes, and numerous organisms
Cryptococcal antigen is almost
invariably detectable in the CSF at
high titer
Opening pressure is elevated in up to
25%: important prognostic and
therapeutic implications
Diagnosis of cryptococcosis
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CSF culture positive
India ink positive
Diagnosis of cryptococcosis
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Cryptococcal antigen in the serum is
highly sensitive and specific for C.
neoformans infection
Positive serum cryptococcal antigen
titer >1:8 is regarded as presumptive
evidence of cryptococcal infection
and warrants antifungal therapy, even
if infection is not subsequently
documented
Cryptococcal Meningitis
Treatment of acute infection
• Drug(s) of first choice:
– Amphotericin B 0.7 mg/kg/d IV +/- flucytosine 100
mg/kg/d x 10-14 days
– then fluconazole 400 mg bid x 2 days, then 400 mg/d
x 8-10 wk or itraconazole 400 mg/d x 8-10 wk
• Alternatives:
– Fluconazole 400 mg/d x 6-10 wk
– Itraconazole 200 mg tid x 3 days, then 200 mg bid x
6-10 wk
– Fluconazole 400 mg/d plus flucytosine 100 mg/kg/d x
6-10 wk
Cryptococcal Meningitis
Suppressive therapy
• Drug of first choice: Fluconazole 200 mg up to 400
mg/day
• Alternatives:
– Amphotericin B 0.6-1 mg/kg 1-3x/wk
– Itraconazole 400 mg/d or 200 mg oral suspension/d
Prophylaxis (CD4 <50)
• Drug of first choice: Fluconazole 200 mg/d
• Alternative: Itraconazole 200 mg/d or 100 mg oral
suspension/d
การป้องกัน cryptococcosis ใน
ประเทศไทย
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ข้ อบ่งชี ้
– CD4 <100/mm3
– เคยเป็ น cryptococcosis มาก่อน
ยาที่ใช้ Fluconazole 400 mg weekly
ผู้ป่วยที่ได้ ยาต้ านไวรัสและมี CD4 > 100-200/mm3 อย่าง
น้ อย 6 เดือน สามารถหยุดยาป้องกันได้
Penicilliosis marneffei
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CD4 +T cell < 100 cells/mm3
Penicillium marneffei, a dimorphic
fungus
Endemic in Southeast Asia (especially
Northern Thailand and Southern
China)
Potential cause of infection in
patients in endemic areas or with a
history of travel to endemic areas
Clinical features of 74 hiv-infected patients
with disseminated P. marneffei infection
Symptoms
Fever
Weight loss
Skin lesions
number (%)
71 (96)
71 (96)
63 (85)
Signs
Temperature > 38.3o C
Skin lesions
Generalized lymphadenopathy
Hepatomegaly
Splenomegaly
72 (97)
63 (85)
62 (85)
48 (65)
17 (23)
Source: Sirisanthana T, et al. Clin Infect Dis. 1998;26:1107-10
Penicilliosis
marneffei
Penicilliosis marneffei
Diagnosis of penicilliosis marneffei
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Wright stain : smear from skin lesion,
node biopsy, marrow biopsy : 2*3-6
um yeast
Culture from skin, bone marrow,LN
Hemoculture
Diagnosis of penicilliosis marneffei
Penicilliosis marneffei
Treatment of acute infection
• Drug(s) of first choice:
– Amphotericin B 0.7-1.0 mg/kg/d IV or Itraconazole 400
mg/d for 10-12 wk
– Amphotericin B 0.7-1.0 mg/kg/d IV x 2 wk then
Itraconazole 400 mg/d for 10 wk
• Alternative: Itraconazole, Ketoconazole or fluconazole
Suppressive therapy
• Drug(s) of first choice: Itraconazole 200 mg/d
Histoplasmosis
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Histoplasma capsulatum, a dimorphic
fungus
Endemic in the Mississippi and Ohio
river valleys of North America,
certain areas of Central and South
America, and the Caribbean
Mycelial form is found in the soil;
particularly soil associated with bird
roosts, and caves
Clinical features of histoplasmosis
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most common: fever and weight loss,
~ 75% of patients
Respiratory complaints, abdominal
pain or gastrointestinal bleeding
5-10% have an acute septic shock-like
syndrome, very poor prognosis
Skin lesions: uncommon, molluscum
contagiosum-like
Histoplasmosis
Disseminated histoplasmosis
Treatment of acute infection
• Drug(s) of first choice:
– Amphotericin B 0.7-1.0 mg/kg/d IV > 7-14 days
– Itraconazole 300 mg bid x 3 days then 200 mg bid x 1012 wk
• Alternative: Fluconazole 400 mg/d
Suppressive therapy
• Drug(s) of first choice: Itraconazole 200-400 mg/d
• Alternatives: Amphotericin B 1.0 mg/kg q 1-2x /wk or
Fluconazole 400 mg/d
การป้องกัน penicilliosis
และ Histoplasmosis ในประเทศไทย
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ข้ อบ่งชี ้
– CD4 <100/mm3 (เฉพาะภาคเหนือ)
– เคยเป็ น penicilliosis มาก่อน
ยาที่ใช้ Itraconazole 200 mg qd
ผู้ป่วยที่ได้ ยาต้ านไวรัสและมี CD4 > 100-200/mm3 อย่าง
น้ อย 6 เดือน สามารถหยุดยาป้องกันได้
Toxoplasmosis
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Toxoplasma gondii
CD4T cell < 100 cells/mm3
Reactivation of infection
Organ involvement
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–
Brain is the most common site
Lungs
Eye: chorioretinitis
GI
Muscle
Transmission
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Ingestion of raw or undercooked
meat that contains cysts
Ingestion of water or food
contaminated with oocysts
Transplacental transmission
Toxoplamosis Encephalitis (TE)
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Cerebritis or brain abscess
Diffuse form less common
Clinical
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Headache
Neurological deficits
Seizure
Alteration of consciousness
Meningismus
Movement disorders
Neuropsychiatric
Diagnosis of toxoplasmosis
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Clinical
CT brain scan or MRI
Toxoplasma titer
Response to treatment
Brain biopsy
Toxoplasmosis
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Multiple brain
lesions
Brain edema
Basal ganglia
Ring
enhancement
CSF findings in TE
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nonspecific
mild mononuclear pleocytosis and
mild to moderate elevations in CSF
protein
Toxoplasmosis Treatment
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First choice
Pyrimethamine 200 mg x 1 then
75-100 mg /d +
Sulfadiazine 1-1.5 g q 6 hr +
Leukoverin 15 mg qd (if available) for
4-6 wks
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Alternative
Pyrimethamine + Leukoverin +
Clindamycin 600 mg q 6 hr
Primary Prophylaxis of
Toxoplasmosis
Indications
1. CD4 cell count < 100/mm3
2. Ig G Ab to Toxoplasma
+ve(IDSA)
Regimens for Primary Prophylaxis
First choice
 TMP-SMX 1 DS qd (AII)
Alternative
 TMP-SMX 1 SS qd (BIII)
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Dapsone 50 mg qd +
Pyrimethamine 50 mg qw +
Leukoverin 25 mg qw (if available)
(BI)
 Dapsone 200 mg qw+
Pyrimethamine 75 mg qw +
Leukoverin 25 mg qw (if available)
(BI)
Regimens for Secondary
Prophylaxis
First choice
 Sulfadiazine 500-1000mg qid +
 Pyrimethamine 25-50 mg/d +
 Leucoverin 10-25mg/d (AI)
Alternative
 Clindamycin 300-450mg q 6-8 hr +
 Pyrimethamine 25-50 mg/d +
 Leucoverin 10-25mg/d (BI)
Summary of toxoplasmosis
management
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Headache + neurological deficit
CT brain scan + serum crypto Ag
Mass lesion in brain
Empiric treat as Toxoplasmosis
Clinical not improve in 2-4 weeks
Repeat CT scan
Further investigation: brain biopsy
Cytomegalovirus (CMV)
• chorioretinitis
• esophagitis
• colitis
• pneumonia
• central nervous system disease
Chorioretinitis
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commonly occurs in patients with CD4 < 50
cells/mm³
accounts for 80% to 90% of CMV disease in
patients with AIDS
common presenting symptoms include
– decreased visual acuity
– perception of floaters
– visual field loss
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Indirect ophthalmologic screening of
patients with a CD4 < 50 cells/mm³ can
detect asymptomatic retinitis
Chorioretinitis
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Ophthalmologic exam. reveals large creamy
to yellowish-white granular areas with
perivascular exudates and hemorrhages
these lesions may occur at either the
periphery or center of the fundus.
lesions generally progress within 2 to 3
weeks and can result in blindness
retinitis often begins unilaterally, but
progression to bilateral disease is common.
systemic CMV disease involving other viscera
may also be present
Chorioretinitis
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DDx: Toxo, Syphilis, HSV, VZV, and TB
Patients with confirmed CMV
chorioretinitis should begin treatment
promptly
A variety of agents have demonstrated
efficacy in delaying time to progression
of retinitis
CMV Retinitis
CMV Retinitis
• Systemic therapy
• Local therapy
Treatment
 Ganciclovir
 Foscarnet
(phosphonoformic
acid)
 Cidofovir
CMV Retinitis Treatment
Systemic Ganciclovir
 Induction:
Systemic Foscarnet
 Induction:
– 5 mg/kg iv over 1 hr
q 12 hr for 2-3 wk
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Maintenance:
– 5 mg/kg iv over 1
hr OD, 5 days/wk
– Or 1,000 mg oral tid
– 60 mg/kg q 8 hr for
2-3 wk
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Maintenance:
– 90 mg/kg per day
CMV Retinitis Treatment
Local Ganciclovir
 Intravitreal
injection 2002,000 µg in 0.1 ml
 Ganciclovir implant
Local Foscarnet
 Intravitreal
injection 1.2-2.4 mg
in 0.1 ml
CMV Retinitis Treatment
Systemic Treatment
 Expensive
 Cover multiple
system infection
 Systemic side
effect
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Local Treatment
Invasive
Higher drug level
Better quality of
life
Mycobacterium avium Complex
(MAC) (MAC = M. avium + M. intracellurare )
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CD4 T cell < 50 cells/mm3
MAC is the most common pulmonary and
disseminated disease ( particularly in
HIV/AIDS)
MAC has been isolated from soil, natural
water, municipal water system, food ,
house, dust , and domestic+wild animals
In HIV/AIDS , infection is acquired
through ingestion > inhalation
No evidence of person-to-person
transmission
Pulmonary MAC
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Clinical feature : chronic cough , low
grade fever, malaise, hemoptysis
Diagnosis :
– CXR : most common pattern : bilateral
lower lobe infiltrate suggestive of
miliary spread, alveolar or nodular
infiltrate & hilar a/o mediastinal
adenopathy
– C/S
Clinical Manifestations and LAB
abnormalities of Disseminated MAC in
HIV+ve
Feature
Positive
Fever
Night sweats
Diarrhea
Abdominal pain
Nausea/vomiting
Weight loss
Lymphadenopathy
Intra-abdominal
Mediastinal
Hepatosplenomegaly
Anemia ( Hb < 8.5 gm/dl)
 Serum alkaline phosphatase
No. of patients
%
120
85
92
54
31
37
87
78
47
35
26
38
54
49
38
39
38
37
10
24
85
53
Disseminated MAC
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Dx
– Positive culture of non-pulmonary,
normally sterile site
– H/C
Treatment
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Preferred regimen
– Clarithromycin 500 mg bid PO +
Ethambutol 15 mg/kg/day PO
– Azithromycin 500-600 mg/day +
Ethambutol 15 mg/kg/day PO
– Severe symptom : two drugs above +
ciprofloxacin 500–750 PO bid or
levofloxacin 500-750 mg qd PO or
rifabutin 300 mg/day PO or amikacin iv
10-15 mg/kg/day
MAC Prophylaxis
Indication
HIV+ve patients with CD4<50 cells/mm3 and
without MAC bacteremia
Rationale
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 Incidence of MAC bacteremia in HIV +ve
with CD4 < 50 cells/mm3
 Morbidity and Mortality with disseminated
MAC
Proven efficacy of available prophylactic
regimens
MAC prophylaxis
Regimen
Clarithromycin
500 mg twice
daily
Azithromycin

Bacteremia
(%)
69
66
1200 mg once
weekly
Rifabutin
300 mg once daily
50
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