Clinical Management of the
Common Opportunistic Infections
Unit 13
HIV Care and ART: A Course for
Physicians
Learning Objectives
 Identify when HIV-related opportunistic infections
(OIs) occur in relation to CD4 cell count
 Describe the syndromic diagnosis and treatment
of common OIs
 Describe the primary and secondary prophylaxis
for common OIs
2
Syndromes Considered in This Unit





Fever
Cough
Headache w/ and w/o neurological findings
Gastrointestinal disease
Rash
3
Opportunistic Infection: Definition
 Infections that develop as a result of damage to
the immune system are called opportunistic
infections or OIs
 These infections take advantage of the
opportunity provided by a weakened immune
system
 Infections tend to appear at predictable stages of
immune deterioration
4
WHO Staging and Disease Correlation
WHO Stage
Some Typical Diseases*
I
Asymptomatic
No symptoms or signs of any illness
Persistent Generalized
Lymphadenopathy
II
Minor Symptoms
Cutaneous Manifestation Folliculitis,
Dermatomal Herpes (Varicella)
Zoster
500 to 350
103 to
104
Oral Candidiasis, Oral Hairy
Leukoplakia, Pulmonary
Tuberculosis
350 to 200
104 to
105
III
Moderate
Symptoms
IV
AIDS-defining
Illness
CD4 Count Viral Load**
103 to
106***
>500
Kaposi’s Sarcoma (KS), Oral KS
<200
MAC, Severe Chronic Herpes
Ulcers, Toxoplasmosis, Cryptococcis
105 to
106
Information courtesy of WHO
*Staging of diseases is approximate and not the same for all individuals
**HIV RNA copies per ml of plasma
***Viral load spikes shortly after infection and then drops quickly when antibodies are formed
5
Principles of OIs with HIV
 Caused by defect in cell-mediated immunity, so common
viral and bacterial infections are not increased
 Exceptions: S. pneumoniae and Salmonella
 Nearly all OIs respond to HAART
 Exception: PML (progressive multifocal leukoencephalopathy)
 Immune Reconstitution Inflammatory Syndrome (IRIS)
 Paradoxical illness associated with improving immunity
 Most common with CD4 <50, following initiation of effective
HAART
 Treatment: continue ART and OI treatment +/- steroids
6
Case 1
 Sisay, a 42 year-old merchant, presented to the OPD
complaining of two weeks high grade and intermittent
fever that usually comes in the afternoon
 He has no complaints except fever. Specifically, he
denies:






Cough or shortness of breath
Abdominal pain, diarrhea or vomiting
Loss of appetite or weight loss
Urinary complaints
Headache or neck pain
Travel to malaria endemic area
7
Discussion
 What would you include in your initial differential
diagnosis?
8
Additional Information
 Sisay had been seen in the local health center
where blood film (BF) was done. He was treated
with antibiotics after the BF turned out to be
negative but showed no improvement
 He was screened for HIV five years back and
was seropositive. He has never been ill and has
received no treatment
9
Discussion
 How does this additional information affect your
differential diagnosis?
 What might you expect to find on physical
examination?
10
Physical Examination
 Healthy looking adult in no
distress
 Vital signs





PR 104/m
RR 18/m
T 39° C
BP 120/80
Wt 80 kg
 Skin: no pallor or icterus
 Lymph nodes: none
palpable
 Chest: clear to
auscultation
 Cardiovascular: normal
findings
 Abdomen: soft, tipped
spleen, no CVA
tenderness
 Musculoskeletal: normal
findings
 No meningeal signs
11
Discussion
 How does this additional information affect your
differential diagnosis?
 How do you investigate this patient?
12
Differential Diagnosis: Infections
 Protozoal: malaria, toxoplasma, leishmania, others
 Bacterial
 Local pyogenic infection of the chest, urinary tract, the CNS,
sinuses, etc
 Bacteremia/septicemia due to Salmonella, Streptococcus,
Staphylococcus, H. influenza, meningococcus, etc
 Mycobacterial infection – M. tuberculosis, atypical mycobacteria
(disseminated)
 Viral infections: upper respiratory tract infections, CMV,
EBV, herpes, others
 Fungal infections: PCP, Cryptococcosis, nocardia,
mycoplasma, disseminated candidal infection, etc
13
Differential Diagnosis (2)
 Neoplasms
 Lymphoma (NHL)
 Kaposi's sarcoma
 Others
 Drug reaction
14
Approach to Fever in HIV Patients
Detailed Clinical History
 Symptoms




Onset
Duration
Pattern
Severity (degree) of
fever
 Accompanying
symptoms, related
complaints
 Past medical history
 Travel history
 Prior illnesses and
treatment
 Drug intake
 Exposure to animals
15
Approach to Fever in HIV Patients
Meticulous Physical Exam
 HEENT, including sinuses
and ears
 Lymphoglandular system
 Chest, including intercostal tenderness and
cardiac evaluation
 Abdominal exam including
PR
 Genitourinary system,
including gynecological
evaluation
 Musculoskeletal
 Integumentary
 CNS, including meningeal
signs and fundoscopy
16
Discussion
 How would you approach the laboratory
evaluation of a patient with fever of
undetermined origin?
 What tests would you include in your initial
evaluation?
 If these were non-diagnostic, what additional
tests would you consider?
17
Laboratory Investigation






CBC including blood film
Blood culture
Mycobacterial culture
Serologic studies
Blood chemistry
Antigen tests (CMV, cryptococcal)
18
Additional Tests
 Chest x-ray and other imaging studies
(sonography, CT scan)
 Lumbar puncture (CSF analysis)
 Biopsy of lymph nodes, skin lesions
 CD4 count, viral load (if not done already)
 Bone marrow, splenic aspirate examination
19
Case Study Discussion
 How would you manage Sisay?
20
Fever Management
 Definitive management of the causative agent
 Therapeutic trial may be considered if tests are non-diagnostic
 Supportive – catabolic febrile state may require various
supportive measures. Based on the patient, consider:





Rehydration
Electrolyte replacement
Calorie replacement
Respiratory support
Palliative control of fever, e.g., with antipyretic, sponging
21
Examples of Fever-causing Agents
 Leishmaniasis
 Mycobacterium avium complex
22
Visceral Leishmaniasis and
HIV Co-infection
 Caused by L. donovanii, an important OI among persons
infected with HIV-1
 Reports mainly from S. Europe, E. Africa, N. and S.
America and Asia
 Most co-infected patients with clinically evident
leishmaniasis have CD4 cell less than 200/µl
 HIV and L. donovanii affect the same cell lines, causing
cumulative deficiency of the immune response
 Leishmania parasites suppress Th1 activity
23
Visceral Leishmaniasis
Clinical Manifestations
 Patients present with fever, organomegaly,
anemia or pancytopenia
 Presentation could be atypical, but VL should be
suspected in those with travel history to endemic
areas
24
Visceral Leishmaniasis
Diagnosis and Treatment
 Diagnosis
 Serology less sensitive in immunocompromised hosts.
 Parasite could be detected in peripheral blood of
immunocompromised patients.
 Bone marrow aspirate more sensitive, and splenic aspirate most
sensitive.
 Treatment
 First line – Pentavalent antimonials (Sb)
 Alternatives – Pentamidine, Amphotericin B
 Relapse and toxicity are common in patients co-infected with
HIV.
25
Mycobacterium Avium Complex (MAC)
Overview
 Ubiquitous in the environment: soil, water, food, house
dust, domestic and wild animals
 History of TB is associated with decreased risk (US,
Sweden, Africa)
 Low CD4 and high VL are predictors of disseminated
disease
 Pre-HAART, MAC was the most common OI, affecting up
to 43% of AIDS patients
 Dramatic treatment impact
26
MAC Clinical Presentation
Symptoms and Signs
 Fever
 Night sweats
 Anorexia
 Weight loss
 Hepatomegaly
 Diarrhea
 Splenomegaly
 Abdominal pain
 Elevated alkaline phosphate
Percentage
93
87
74
60
42
40
32
28
95
27
MAC Fever with Treatment
Tx
41
T
E
M
37.5
BC +
P
BC 5
1
2
3
4
Days
28
MAC Treatment
 At least two medications
 Clarithromycin 500mg bid po (or Azithromycin 500600 mg qd po) AND
 Ethambutol 15mg/kg qd po
 Add 3rd or 4th drug if: CD4 count <50; high
mycobacterial loads; or absence of effective
ART




Rifabutin 300 mg qd po
Ciprofloxacin 500-750 mg bid po
Levofloxacin 500 mg qd po
Amikacin IV 10-15mg/kg qd
29
Case Two
 Belaynesh is a 34 year-old woman presenting
with two months history of non productive cough,
and two weeks of fever with progressively worse
shortness of breath
 Also notes three months of generalized body
weakness, loss of appetite and 8 kg. weight loss
 Her husband died two years ago of “bird”
(pulmonary disease) leaving her with two
children who are now 12 and 14
30
Discussion
 What would you include in your initial differential
diagnosis?
31
Differential Diagnosis
 Mycobacterial or
bacterial pneumonia





Tuberculosis
Strep, staph
H. influenzae
Legionella
Others
 Viral pneumonia
 CMV
 Influenza virus
 Fungal pneumonia




Pneumocystis
Cryptococcal
Nocardia
Histoplasmosis etc.
 Neoplastic
 Kaposi sarcoma
(pulmonary Kaposi)
 Lymphoma
32
On examination . . .




She was in respiratory distress
Mild cyanosis of the finger tips
Bilateral fine diffuse rales
Vital signs





BP
Temp
Pulse
Resp
WT
110/70 mm Hg
38 oC
112/m
36/m
48 Kgs
What tests would you like to order?
33
Potential Diagnostic Tests






CBC
Sputum culture & stain for AFB, bacteria, fungal
CXR
HIV serology
LFT, RFT, etc
Bronchoalveolar lavage (BAL)
 Methenamine silver stain for Pneumocystis
 CD4
 Viral load
34
Belaynesh’s Laboratory Results








WBC
TLC
Hgb
Gram stain
AFB
HIV serology
CD4
CXR
2500/mm3
750/mm3
12g/dl
no gram positive diplococcus
negative 3x
positive (done after counseling)
72 cells/µl
as follows
35
PCP Chest X-Ray
36
Discussion
 How do these results change your differential
diagnosis?
 How would you manage this patient?
37
Focused Differential Diagnosis
 PCP
 Pulmonary tuberculosis (atypical appearance) in
late stage HIV disease
 Viral interstitial pneumonia, e.g., CMV
 PCP superimposed with tuberculosis
(or some other combination of pathogens)
38
Pneumocystis Jiroveci Pneumonia
 Most humans infected early in life
 Diagnosis via induced sputum or
bronchoalveolar lavage (bronchoscopy)
 Stains with Wright-Giemsa, methenamine silver, and
direct immunofluorescence
 Typical presentation
 Non-productive cough
 Exertional dyspnea
 Gradual fever
39
Pneumocystis Treatment
 Standard regimen:
 Cotrimoxazole (15-20 mg TMP + 75-100 mg
SMX)/kg/day in 3 doses IV or PO for 3 weeks
 Alternative treatments:
 Dapsone 100 mg qd + Trimethoprim 15 mg/kg/day
PO divided tid x 3 wks
 Pentamidine 4 mg/kg IV qd x 3 weeks
 Primaquine 15-30 mg qd + Clindamycin 450 mg po
q8h x 3 wks
 Atovaquone 750 mg bid with food x 3 wks
40
Adjunctive Corticosteroids in
Pneumocystis Therapy
 Adjunctive corticosteroids are indicated for severe
hypoxemia (pO2<70, AaDO2>35)
 Reduces mortality by 50%
 Start within 72 hours of presentation
 Regimen
 Prednisone 40 mg po bid x 5 days, followed by
 40 mg qd x 5 days, followed by
 20 mg qd x 11 days
 No benefit for salvage therapy or mild episodes
 Use cautiously if diagnosis is not confirmed, and watch
for other OIs
41
Benefit of Corticosteroids in
Pneumocystis Therapy
 Survival in PCP depends on patient’s level of
oxygenation
 Adjunctive corticosteroids can have a significant effect
on clinical outcome, including survival
 Begin within 72 hours of specific antipneumocystis therapy
 Caution should be taken in treating patients with
tuberculosis, fungal pneumonia, or pulmonary Kaposi's
sarcoma
 Steroids can have detrimental effect
 Vigorous attempts to confirm a diagnosis of PCP should be
made rather than initiating adjunctive corticosteroids empirically
42
Pneumocystis Prophylaxis
Indications
 Primary prophylaxis (to prevent disease)
 CD4 < 200/mm3
 HIV-associated oral candidiasis
 Unexplained fever
 Secondary prophylaxis (after pneumonia, to
prevent recurrence)
 Prior episode of PCP
43
Pneumocystis Prophylaxis
Agents
 Standard regimen
 Cotrimoxazole (TMP/SMX) 1 tab daily
 Alternate regimens
 Dapsone 100mg daily
 Atovaquone 1.5 gm PO qd
 Inhaled pentamidine 300 mg monthly
 Duration of treatment: lifelong, but
 May safely discontinue if immune system restored from
ART
 Must have CD4 > 200 for 3 months
44
Resolution
 Belaynesh was started with Bactrim and steroids
 After seven days of treatment she started to
show marked clinical improvement
 She was discharged with: 1) oral Bactrim, 2) an
appointment to be seen at the OPD, and 3)
instructions to return before her appointment if
she worsened
45
Case Three
 Amare, a 38 year-old English teacher from Bahir
Dar, presents to the general OPD with 10 days
history of fever and headache
 For the past two days he has vomited any
ingested matter
 Today he had one seizure with inability to
communicate
46
Additional Information
 Amare’s sister also reports:
 Amare has had slight right-side body weakness and 2
days difficulty with speech
 He had pulmonary tuberculosis 2 years ago
 He received an HIV positive test result 6 months ago,
after he lost considerable weight for no apparent
reason. He shared this information with her, but was
afraid to seek medical care
47
Discussion
 What would you include in your initial differential
diagnosis?
48
Additional Findings
 Chronically ill appearing
 Vital signs
 Temp. 38.8° C
 Wt 52 Kg
 Facial seborrhoeic dermatitis
 Fundoscopy – bilateral papilledema
 Right extremity power 3/5, brisk DTR
49
Discussion
 How does this additional information change
your initial differential diagnosis?
 What tests would you like to order?
50
Test Results









WBC
3500/mm3
TLC
800/mm3
Hgb
10 g/dl
Blood Film negative
VDRL
non-reactive
ESR
85 mm/hr
CXR
normal
Node FNA pending
Serology for toxoplasma and CT of the brain could not
be done as these investigations are not available.
51
Discussion
 How does this additional information change
your thinking?
 How would your thinking change if you knew the
brain CT showed 2 ring-enhancing lesions?
 How would your thinking change if the
toxoplasma serology were negative?
52
(Partial) Differential Diagnosis




Cerebral toxoplasmosis
Tuberculoma
CNS lymphoma
Cryptococcosis
53
Toxoplasmosis Facts
 Is caused by Toxoplasma gondii
 Cats are definitive host; excrete organism in
feces
 Cysts also found in inadequately cooked meat
 Seropositivity in Ethiopia reaches 80%
 For an immunosuppressed patient with focal
neurologic signs, cerebral toxoplasmosis is the
most likely diagnosis
54
Treatment Considerations
 The presentation is so characteristic that many
guidelines suggest routine treatment for
toxoplasmosis
 A lack of response to such therapy indicates
other possible conditions:
 Central nervous system lymphoma
 Tuberculoma
 Cryptococcoma
55
Treatment Response
 With empiric treatment for Toxoplasmosis, what
should we expect?
 Nearly 90% of patients will respond clinically within
days of starting therapy
 Radiologic evidence of improvement should appear
by 14 days following treatment initiation
56
Cerebral Toxoplasmosis
 When no imaging is available, it is appropriate to
initiate treatment for two weeks to assess for
clinical improvement
 If improvement occurs, continue treatment until
the CD4 count responds to ART and increases
to more than 200
 Use the maintenance therapy after initiating
acute therapy for 6 weeks
57
Toxoplasmosis Brain CT Scan
58
Courtesy of HIV Web Study, www.hivwebstudy.org
Toxoplasmosis Treatment
 Loading dose of Pyrimethamine 200 mg once,
followed by:
 Pyrimethamine 50-75 mg/day, plus
 Sulfadiazine 1.0-1.5 gm q 6 hrs, plus
 Folinic acid 10-20 mg/d
 Corticosteroids (dexamethasone 4mg PO or IV
q6hrs) used if cerebral edema present, and
discontinued as soon as clinically feasible
59
Additional Treatment Questions
 How long will you continue the primary treatment
for toxoplasmosis?
 Could alternatives to the standard regimens be
used?
 Which drugs do we commonly use to treat
toxoplasmosis in the Ethiopian context?
 What about suppressive therapy in this patient?
60
Primary Treatment Duration
 Duration of Rx is 6 weeks, or 3 weeks after
complete resolution of lesions on CT (if repeat
CT is available)
61
Alternative Regimens
 Pyrimethamine and Leucovorin (standard dose)
PLUS Clindamycin 600 mg q 6 hrs, or
 Cotrimoxazole (TMP 5 mg + SMX 25 mg)/kg IV
or PO bid, or
 Atovaquone 1.5 gm PO bid, or
 Pyrimethamine and Leucovorin (standard dose)
PLUS Azithromycin 900-1200 mg PO qd
62
Ethiopian Toxoplasmosis Treatment
 In Ethiopian context, Fansidar (Pyrimethamine
plus Sulfadoxine) is used
 A loading dose of two tabs of Fansidar bid for 2 days,
followed by
 Fansidar one tab daily for life
63
Suppressive Therapy
 Pyrimethamine 25 mg + sulfadiazine 500 mg +
folinic acid 10-25 mg PO qd
 Cotrimoxazole DS tablet daily
 Can be stopped when the CD4 count remains ≥
200 for 6 months
64
Are Therapies Potentially
Toxic?
YES
Common Toxicities
 Bone marrow suppression, including:
 Thrombocytopenia
 Leucopenia
 Anemia
 If signs of folate deficiency develop, reduce the
dosage or discontinue the drug
 Folinic acid (Leucovorin) 5 to 15 mg daily should
be administered with pyrimethamine
66
Primary Prophylaxis for Toxoplasmosis
 When is it indicated?
 What is used?
67
Toxoplasmosis Primary Prophylaxis
 Indications:
 Positive toxoplasma serology, and
 CD4 count <100 cells/mm3
 Regimens
 TMP/SMX DS tab daily (preferred)
 TMP/SMX 3 times weekly
 TMP/SMX SS tab daily
 TMP/SMX prophylaxis serves dual purpose: for
PCP and to prevent toxoplasmosis of the brain
68
Toxoplasmosis Primary Prophylaxis (2)
 Alternative regimen
 Dapsone 50 mg/day, plus
pyrimethamine 50mg weekly, plus
folinic acid 25 mg weekly (if available)
 Primary prophylaxis can be stopped if CD4
count >200 cells/mm3 for more than three
months following HAART
69
Retinal Toxoplasmosis
Courtesy of: C. Stephen Foster M.D., Copyright © 1996-2005,
All Rights Reserved
70
Variation on Headache
 What if the patient did not have a seizure or
focal neurological findings, but still had
persistent fever and severe headache?
 How would this change your thinking and/or your
management?
71
Additional Information
 No neck stiffness
 LP was done:





Opening pressure = 300 mm H2O
30 WBC/mm3
Protein 35 gm%
Glucose: normal
India ink stain: pending
72
Discussion
 How do you interpret these findings?
 What is normal OP?
 What additional tests will you do?
73
Additional Information
 Results from additional tests:
 India ink was positive for Cryptococcus
 CSF Cryptococcal culture: Positive
 Other tests in the CSF: Negative
74
Cryptococcal Meningitis




Caused by a yeast-like fungus, C. neoformans
Infection acquired through inhalation
Occurs in advanced disease (CD4<100)
Rarely, presents as pneumonitis, or as
disseminated disease that includes skin
(umbilicated vesicles, like molluscum)
 Clinical manifestations may be subtle
75
Clinical Signs of
Cryptococcal Meningitis
Clinical Manifestations
% of Cases
Headache
70-90
Fever
60-80
Meningeal signs
20-30
Photophobia
6-18
Seizures
5-10
76
Cryptococcal Meningitis Treatment
 Amphotericin 0.7 mg/kg/day IV plus flucytosine 25 mg
PO qid for 2 weeks followed by Fluconazole to 8 weeks
 If potassium drops dangerously, switch amphotericin to
fluconazole PO
 If Amphotericin not available, use Fluconazole 400-800
mg/day
 Treatment continued for 8-10 weeks, or until CSF is
sterile
 After treating acute illness, continue preventive therapy
(Fluconazole 200 mg PO qd) until asymptomatic and
CD4 > 200 x 6 months
77
Additional Patient
Management Issues
 HAART
 Adherence issues
 Side effects
 Drug interactions, etc
 Prophylaxis for PCP
 Support and follow up
 Nutrition and healthy lifestyles, including
disclosure and risk reduction issues
78
Case Four
 Sara, a 32 year-old accountant, presented with
retrosternal pain associated with swallowing of
both solid and liquid foods of two weeks duration
 She also reports generalized body weakness
and weight loss
 One month back she developed whitish oral
lesions, treated with topical antifungals
79
Discussion
 What would you include in your initial differential
diagnosis?
 What would you expect to find on physical
examination?
80
Physical Examination
 She was chronically sick looking
 Vital signs were all in normal range
 Small, unremarkable posterior cervical lymph
nodes
 Extensive oral candidiasis
 Chest clear
 No other pertinent findings
81
Discussion
 How does this additional information affect your
differential diagnosis?
 How do you investigate this patient?
82
Differential Diagnosis







Esophageal candidiasis
CMV esophagitis
HSV esophagitis
Kaposi's sarcoma or lymphoma
Idiopathic ulcers (aphthous ulcers)
Gastroesophageal reflux disease
Combination of 2 or more
83
Diagnostic Interventions
 KOH from oral lesion
 Barium swallow
 Endoscopy and tissue biopsy





Tissue staining for CMV
Fluorescent antibody tests
Antigen detection tests (CMV & HSV)
Polymerase chain reaction (PCR)
Viral culture
 Therapeutic trials with systemic antifungals
84
Therapy
 Esophageal candidiasis would be the most likely
diagnosis in this patient
 Fluconazole 200mg/day PO (up to 400mg/day) for 1421 days
 Alternative treatments
• Ketoconazole 200-400 mg PO qd for 14-21 days
• Itraconazole 200 mg PO qd for 14-21 days
85
Therapy (2)
 CMV esophagitis requires systemic ganciclovir
 Oral ganciclovir has poor oral absorption so IV
treatment is preferred
 HSV esophagitis may be treated with acyclovir,
valacyclovir, or famciclovir
 Kaposi sarcoma should be treated with HAART
and/or other therapies as described previously
 Idiopathic ulcers may respond to oral steroids
 Reflux is treated as for non-HIV patients
86
CMV
 Typically does not cause disease until CD4 <50
 Manifestations in HIV patients:
 Retinitis
• Unilateral or bilateral visual disturbance
• Confirmed by retina exam showing “scrambled eggs &
ketchup” (exudates & hemorrhages)
 GI disease
• Esophagitis
• Colitis with watery diarrhea, abdominal pain
87
CMV Retinitis
88
© Slice of Life, Suzanne S. Stensaas
Case Five
 Solomon, a 42 year-old farmer, presents to the
OPD with a one month history of watery diarrhea
 He reports minimal abdominal pain and bloating,
with no tenesmus
 He also reports generalized body weakness and
significant weight loss
89
Discussion
 What would you include in your initial differential
diagnosis?
90
Additional Information
 He was recently admitted for this problem and
treated with IV fluids and oral antibiotics
 Treatment helped a little but the problem
recurred
 He was screened for HIV and was found positive
but he was not started with ARV
 Other diagnostic tests were negative
 He was treated for tuberculosis five years back
91
Discussion
 How does this additional information change
your initial differential diagnosis?
 What would you expect to find on physical
examination?
92
Physical Examination
 He is chronically ill
appearing and emaciated
 Vital signs





PB 90/60mm Hg
PR 110/m
RR 18/m
T 36oC
Wt 46 kg
 Oral candidiasis
 No lymphadenopathy
 Normal chest,
cardiovascular
 Soft abdomen, no masses
or organomegaly
 Old herpes zoster scar on
the trunk
 No other abnormal findings
in the other systems
93
Discussion
 How does this additional information change
your initial differential diagnosis?
 What laboratory tests would you perform?
94
Differential Diagnosis
 Enteropathogenic bacteria
 Shigella
 Salmonella
 E. coli
 CMV
 Mycobacteria
 M. tuberculosis
 M. bovis
 Parasites





E. histolytica
G. lamblia
Cryptosporidium parvum
Isospora belli
Strongyloides stercoralis,
others
95
Laboratory Diagnosis
 Direct microscopy of stool, including leukocyte
stain
 Stool culture
 AFB stain
 Modified AFB stain
 Endoscopy and colon biopsy
 Assessment of related effects (CBC, LFT, RFT,
electrolytes, blood sugar, U/A, VDRL, CD4, viral
load)
96
Diagnosis and Treatment of Common
Causes of Diarrhea in AIDS Patients
Agent
E. histolytica
Giardia
CD4
Symptom
Diagnosis
Stool
any bloody stool, colitis
microscopy
any Watery diarrhea
“
Rx
Metronidazole
“
Cryptosporidium <150 Watery diarrhea
Modified AFB
?paromomycin
Isospora belli
<100 Watery diarrhea
Modified AFB
TMP-SMX
Microsporidium
<50 Watery diarrhea
Giemsa stain
Albendazole
CMV
<50
Watery to Bloody
stool, colitis
Biopsy, barium
Ganciclovir
study
97
Case Six
 Your colleague working in a nearby health center
calls you to ask for advice in managing an HIV
patient
 The patient has been well, without illness, but
now presents concerned about a new skin lesion
98
Skin Kaposi
99
Courtesy of the Public Health Image Library/CDC/ Dr. Steve Kraus
Additional Information
 On physical examination, you also note a lesion
in the eye
100
Conjunctival Kaposi
101
Courtesy of Paul T. Finger, MD, FACS. www.eyecancer.com
Kaposi Sarcoma Epidemiology
 Was most common cancer at beginning of AIDS
epidemic
 With use of HAART, KS incidence has declined by 66%
between 1989 and 1997, and has likely declined further
 Decline in KS may be due to:
 HAART-induced HIV down-regulation with immune recovery
 Change in sexual practice may have decreased transmission
102
KS Etiology and Pathogenesis
 Presumed due to Human Herpes Virus 8 (HHV8)
 Studies of MSM have shown that HHV-8 may be
sexually transmitted
 Multiple heterosexual contacts is a risk factor for
HHV-8 in Africa
 Other transmission via saliva; parenteral; from
mother to child
103
KS Clinical Manifestations
 Can affect almost any organ system
 Most common sites include:
 Skin: flat to nodular lesions; can progress to
significant infiltration of skin with necrosis
 Oral cavity: flat to invasive lesions
 GI tract: can have KS anywhere in GI tract, which can
cause intestinal blockage and bleeding
 Pulmonary: can spread along bronchi and vessels
104
Genital and Oral Lesions
Courtesy of HIV Web Study, www.hivwebstudy.org
Courtesy of the Public Health Image Library/CDC/ Sol Silverman,
Jr., D.D.S., University of California, San Francisco
105
Kaposi Sarcoma Diagnosis
 Skin and oral lesions are typically diagnosed by
visual exam; skin biopsy is most accurate
(although invasive) way to make diagnosis
 Lung and GI-tract lesions need endoscopy and
biopsy for definite diagnosis
 Resolution of skin lesions with HAART supports
a presumptive diagnosis
 Testing for HHV-8 is not indicated for clinical
management, and treating HHV-8 is ineffective
106
Kaposi Sarcoma Treatment
 Local therapy for skin lesions






Alitretinoin gel (35-50% response)
Local radiation (20-70% response)
Intralesional vinblastine/vincristine (70-90% response)
Cryotherapy (85% response)
Photodynamic therapy
Surgical excision
 Systemic therapy failure of local therapy or
extensive disease
107
Molluscum Contagiosum
 Small, firm,
umbilicated
papules
 Typically, resolve
completely
with HAART
 Persist for months in
patients with significant immunosuppression
 Implicated papules of Molluscum contagiosum
and Cryptococcus have the same appearance
 Diagnosis is proven through tissue biopsy
108
Molluscum Contagiosum
Treatment
 The goal of treatment is to remove the soft
center from each lesion.
 Various methods are available, including:




Curettage
Chemical destruction with concentrated phenol
Cryotherapy
Electrocautery
 Generally lesions disappear with HAART.
109
Pruritic Papular Eruption (PPE )
 Multiple, chronic, pruritic, hyperpigmented papules
distributed symmetrically on the trunk and extremities
 May be one of the earliest clinical manifestations of HIV,
despite being a marker of advanced disease
 Etiology unclear
 Primarily a clinical diagnosis
 Eosinophilia and elevated IgE are usual findings
 Success has been reported with UVB light, with or
without oral antipruritics, as well as pentoxifylline
110
Pruritic Papular Eruption (PPE )
Photograph courtesy of Charles Steinberg MD
111
Seborrheic Dermatitis
 Characterized by reddish scaling eruption that
favors the scalp, ears, sternum, face, axillae and
crural folds
 Occasionally the scales can be yellowish or
greasy appearing
 Topical treatment with corticosteroid creams are
helpful
 Systemic steroids are seldom needed
 Medicated shampoos can help the dandruff
associated with scalp involvement
112
Seborrheic Dermatitis
113
Courtesy of Dr. R. Ojoh, www.thachers.org
Eosinophilic folliculitis
 Characterized by multiple sterile follicular
pustules and urticarial papules on the face,
trunk, and extremities
 Often confused with bacterial folliculitis
 Involved follicles show spongiotic changes with
eosinophilic and lymphocyte infiltration of the
epidermis
 Eosinophilia, leukocytosis, and elevated IgE
levels are often present
 Topical steroids are the mainstay of treatment
114
Eosinophilic Folliculitis
115
© Slice of Life and Suzanne S. Stensaas
Herpes (Varicella) Zoster
 Occurs due to reactivation of varicella zoster
 In HIV:
 Often multi-dermatomal
 May be recurrent
 Occurs early in disease; first episode usually in
patients with CD4 count>350 cells /mm3
 If treated within 72 hrs of the first appearance of
symptoms (pain, redness, papular rash) the
progress/appearance of vesicular lesions may
be arrested
116
Varicella Zoster Lesions
Typical Distribution
117
Courtesy of the Public Health Image Library/CDC
Varicella
Zoster Lesions
Zoster
Sequence
Typical Distribution (2)
118
Courtesy of Tom Thacher, MD
Varicella Zoster Treatment
 Famciclovir 500 mg po tid for 7-10 days
 Valacyclovir 1 gm po tid for 7-10 days
 Acyclovir 800mg po 5x/day for 7-10 days
 Superimposed bacterial infection should be treated with
antibiotics.
 Zoster Ophthalmicus can cause blindness
 Treatment - Acyclovir 800mg po 5x daily, plus
 Topical acyclovir ointment applied 5x daily with topical midriatics
to prevent synechae formation and corneal opacity
119
Effect of Use of PIs on Mortality
Copyright © 1998 Massachusetts Medical Society
120
Key Points
 Infections that develop as a result of damage to
the immune system are called opportunistic
infections or OIs
 Most OIs and complications of HIV develop
when the CD4 count drops below 200/mm3
 OIs are leading causes of morbidity and
mortality in HIV-infected persons
121
Key Points
 Common OIs in Ethiopia include TB, PCP,
Toxoplasmosis, and Cryptococcus
 Many OIs are both preventable and treatable
 Standards exist for diagnosing and treating
common HIV-related OIs
 After appropriate OI treatment, assessment for
ART therapy is needed
122