Post on 31-Dec-2015
1
Overview of Opportunistic Infections
in HIV/AIDS
HAIVNHarvard Medical School AIDS
Initiative in Vietnam
2
Learning Objectives
By the end of this session, participants should be able to:
Explain the relationship between CD4 count and incidence of specific opportunistic infections (OIs)
Describe the most common OIs in Vietnam including:• clinical presentation• diagnosis • national treatment recommendations
3
What is an Opportunistic Infection (OI)?
An infection caused by pathogens that usually do not cause disease in a host with a healthy immune system
A compromised immune system presents an "opportunity" for the pathogen to infect
4
What is the Relationship Between CD4 Count and OIs?
The lower a person’s CD4 count is, the more vulnerable he/she is to opportunistic infections (OIs)
Different infections can occur based on how weak a person’s immune system is
The level of CD4 count determines the OIs for which a person is at risk
5
Sample OIs per CD4 Count
CD4 Count OI / Condition> 500/mm3 Candidal vaginitis
Persistent generalized lymphadenopathy
200-500/mm3 Pneuomoccal pneumoniaPulmonary tuberculosisHerpes zosterOropharyngeal candidiasis (Thrush)
< 200/mm3 Pneumocystis jiroveci pneumoniaMiliary/extrapulmonary TB
< 100/mm3 Candida Esophagitis PenicilliosisToxoplasmosisCryptococcosis
< 50/mm3 Mycobacterium avium complex (MAC)Disseminated cytomegalovirus (CMV)
6
Key Principles of OI Diagnosis and Treatment
Accurate diagnose of OIs require consideration of: • Clinical features• Severity of immunosuppression• Results of specific lab tests
Patients often have multiple OIs at the same time
Drug-drug interactions are an important consideration in the management of OIs
7
Clinical Presentation, Diagnosis
and Treatment of Major OIsin Vietnam
8
What are Common OIs in Vietnam?
Oral Candidiasis (Thrush)
Tuberculosis Penicilliosis Cryptococcal
Meningitis PCP Cerebral
Toxoplasmosis
Cytomegalovirus (CMV) Retinitis
Mycobacterium Avium Complex (MAC)
Cryptosporidiosis Isosporiasis and
Cyclosporiasis
9
Oral Candidiasis (Thrush)
Most patients have no symptoms
Shows as white plaques on palate, gums
Treatment:1. Fluconazole
150mg/day for 7 days
2. Ketoconazole 200mg bid for 7 days
White plaques on palates, removable by tongue blades
10
Candida Esophagitis
Patients complain of: pain in throat or
chest when swallowing
food getting “stuck” Treatment
Flu 200mg/day for 14 days
Itra 400 mg/day for 14 days
Keto 200 mg bid for 14 days
11
Tuberculosis (1)
TB is the most common OI in Vietnam and the most common cause of death among HIV patients
Clinical symptoms of pulmonary TB include fever, cough, night sweats, weight loss, and bloody sputum
Extrapulmonary TB is more common in HIV+ compared to HIV- patients
12
Tuberculosis (2)
Diagnosis: Clinical symptoms CXR Sputum AFB
smear Bronchoscopy
where available Tissue biopsy
(lymph nodes)
Right upper lobe infiltrate
13
Pneumocystis jiroveci Pneumonia (PCP) (1)
Clinical manifestations include:• gradual onset of shortness of breath• dry cough• fever
Lung sounds may be clear or have faint crackles
Hypoxia is common Elevation of LDH is common but
nonspecific CD4 <200 (though occasionally higher)
14
Pneumocystis jiroveci Pneumonia (PCP) (2)
Typical CXR • bilateral diffuse
infiltrations Atypical CXR
• normal result• blebs and cysts• lobar infiltrates
Suggestive CXR• pneumothorax
15
PCP Diagnosis (1)
Diagnosis can be made clinically
Empiric treatment should be started if the diagnosis is suspected
Definitive diagnosis is made by sputum smear and stain Fluorescent stain
PCP Treatment
Condition, Medication
Treatment regimen
Trimethoprim-sulfamethoxazole (Cotrimoxazole)
• 15-20 mg/kg/day (of TMP) for 3 weeks
For severe cases, add prednisone (for 21 days)
• 40 mg twice daily for 5 days, then:• 40 mg daily for 5 days then: • 20 mg/day for 11 days
Then, chronic suppressive therapy: Cotrimoxazole
• 160/800 mg daily• Discontinue when CD4 >200 for 6
months on ARV
National Treatment Protocol
17
Case Study: Duc (1)
Duc, a 30 year-old HIV positive man, presents to OPC with cough of 3 weeks duration• Scanty whitish sputum • Low grade fever• Developed shortness of breath one week ago• On examination he was in respiratory distress
with RR of 40/min and cyanosis What are the likely causes? What important tests would you request?
18
Case Study: Duc (2)
Results of tests:
Sputum AFB: negative 3 times
CXR: bilateral infiltrates
CD4: 110/mm3
19
Penicilliosis (1)
Causative agent Penicillium marneffei• First isolated in 1956 in Vietnam from the
bamboo rat Endemic in southeast Asia and
southern China First case reported in an AIDS patient
was in Vietnam in 1996 Majority of cases occur in patients
with CD4 cell counts < 100Source: Hien TV et al. CID 2001;32:e78-80.
20
Penicilliosis (2)
Most common signs and/or symptoms include:• Fever• Weight loss• Skin lesions• Lymphadenopathy• Hepatomegaly• Splenomegaly• Anemia• Elevated AST, ALT
21
Typical Skin Lesions of P. MarneffeiCutaneous papules with central necrotic umbilication.
May be confused with molluscum contagiosum or disseminated cryptoccocus.
22
Penicilliosis - Diagnosis
P. marneffei cultures (blood or skin lesions) produce a distinct red diffusible pigment
Culture
Wright stain of skin lesions
Direct microbiological
exam
23
Penicilliosis - Treatment
National Treatment Protocol
Condition Treatment RegimenSevere cases •Amphotericin B 0.7mg/kg/day IV for 2
weeks•Then itraconazole 200mg 2x/day for
next 8-10 weeks
Mild to moderate cases
• Itraconazole 200mg 2x/day x 8 weeks
Maintenance therapy
• Itraconazole 200 mg/day•Discontinue when patient is on ART
and has CD4 count > 200 cells/mm3 ≥ 6 months
24
Cryptococcal Meningitis (1)
Clinical manifestations: Headache, fever, nuchal rigidity,
fatigue, mental disorders Course can be chronic (months) Meningeal signs may be absent in
advanced AIDS cases CD4<100
25
Cryptococcal Meningitis (2)
Diagnosis of CM is done by examining cerebral spinal fluid (CSF) after performing a lumbar puncture• Opening pressure• CSF parameters (cell count, protein,
glucose)• Microbiology
India Ink stain Cryptococcal antigen test CSF culture
26
Cryptococcal Meningitis - Treatment
Condition Treatment RegimenPreferred regimen
•Amphotericin B 0.7mg/kg/day IV for 2 weeks
•Then Fluconazole 800- 900 mg/day for next 8 weeks.
Mild cases or if amphotericin not available
•Fluconazole 800-900 mg/day for 8 weeks
Maintenance therapy
•Fluconazole 150-200 mg/day•Discontinue when patient is on ART
and has CD4 count > 200 cells/mm3 ≥ 6 months
*With management of elevated intracranial pressure
27
Cerebral Toxoplasmosis
Seen in patients with CD4<100 Clinical manifestations:
• Fever• Headache• Confusion• Motor weakness• Focal neurological deficit• Seizures, stupor, coma
28
Cerebral Toxoplasmosis – Diagnosis (1)
MRI of cerebral toxoplasmosis showing 2 ring enhancing lesions – “lighting up” with intravenous contrast
29
Cerebral Toxoplasmosis – Diagnosis (2)
Empiric treatment with good clinical response• (+/-) improvement of brain imaging
Positive blood serology (IgG) to T. gondii• Indicates prior infection• Negative serology makes cerebral
toxoplasmosis less likely Brain or tissue biopsy
• crescent/banana shaped tachyzoites
30
Cerebral Toxoplasmosis: Treatment
Treatment Type
Medication Regimen
Acute Treatment
Cotrimoxazole: TMP 10 mg/kg/day intravenously or orally for 3-6 weeks
OR:
Pyrimethamine: 200 mg loading dose, then 50-75 mg once daily
+ Sulfadiazine: 2-4g/initial dose, then 1- 1.5 g every 6 hours for 3-6 weeks
Maintenance Therapy
Pyrimethamine: 25-50 mg/day+ Sulfadiazine: 1g x every 6 hoursOR:Cotrimoxazole 960 mg (SMX 800mg / TMP 160mg) orally once per day Discontinue when patient is on ART with CD4 count > 100 cells/mm3 ≥ 6 months
31
Case Study: Huong
Huong, a 31 year-old HIV-positive woman from Hanoi, presents with weakness of left upper and lower extremities for 5 days duration• Complains of fever, severe headache and
vomiting for last 2 weeks• Not taking any medication• Examination revealed a confused woman
with weakness of left extremities but no meningeal signs
What is Huong’s differential diagnosis?
32
Mycobacterium Avium Complex (MAC)
Prevalence unknown in Vietnam • 3% of cohort of AIDS
patients in Hanoi Manifestations
• CD4 < 50 • Fever• Weight loss• Lymphadenopathy• Hepatosplenomegaly• Anemia
Diagnosis• Blood culture• Bone marrow and
lymph node biopsies with culture
Treatment• Clarithromycin or
azithromycin PLUS ethambutol
33
Cytomegalovirus (CMV) Retinitis
Presentation: CD4 < 50 blurred vision blind spots “floaters” blindness painless condition Treatment: Ganciclovir
intravitreal* or intravenous injections
ART
* Ganciclovir intravitreal injections are available at the national level in both north and south Vietnam
34
Cryptosporidiosis (1)
Caused by infection with C. parvum • generally infects small bowel mucosa
Transmission• ingestion of the cysts (usually in water
contaminated with feces) Can affect patients at any CD4 count
• CD4 < 100 are at highest risk for most severe infection
35
Cryptosporidiosis (2)
Clinical presentationacute or subacutenon-bloody, watery diarrheanausea and/or vomitinglower abdominal crampsfever can occur
DiagnosisModified AFB stain
TreatmentSupportive ART to raise CD4 count
36
Isosporiasis and Cyclosporiasis
Transmitted by ingestion of contaminated food and water
Clinical presentation• chronic voluminous watery diarrhea • abdominal cramps, nausea/vomiting• weight loss
Treatment• TMP-SMX 2 DS tablets twice or three times
daily for 2 – 4 weeks• ART to raise CD4 counts
37
Case Study
A 32-year-old IDU comes to the clinic complaining of persistent diarrhea that started five months earlier
You do a CD4 count and stool exam• His CD4=70• His stool reveals cryptosporidium
How would you classify his clinical stage?
With a CD4 count of 70, what other OIs is he at risk for?
38
Key Points
An OI is caused by pathogens that usually do not cause disease in a healthy host
Knowing a PLHIV’s CD4 count can help clinician better diagnose an OI
Accurate diagnose of OIs require consideration of: • Clinical features• Severity of immunosuppression• Results of specific lab tests
39
Thank you!
Questions?