Introduction to the diagnosis and
management of common opportunistic
infections (Ols)
Module 4 Sub module OIs
Opportunistic Infections
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Pneumocystis carinii
pneumonia (PCP)
Penicilliosis
Recurrent pneumonia
Cryptococcus
Toxoplasmosis
Oesophageal
candidasis
Mycobacterium Avium
Complex (MAC)
Cytomegalovirus (CMV)
Natural course & common clinical manifestations
1000
900
800
700
600
500
400
CD4 300
COUNT
200
100
50
<50
0
TB
TB
HZV
OHL
Oral candida
PCP
Cryptococcal meningitis
PPE
CMV
MAC
TB
Cryptosporidial diarrhea
0369 1
Months
2
3
4
5 6
Years
TB
7
8
9
10
Common opportunistic infections
The most common opportunistic infections
Tuberculosis
PCP
Cryptococcosis
Candidiasis, oesophageal
Pneumonia, recurrent
0
5000
10000
15000
20000
Division Epidemiology, Department of Communicable Diseases Control, MOPH, Thailand
25000
Pneumocystis Carinii Pneumonia (PCP)
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Organism

Pneumocystis Carinii

Very common

CD4 count < 200 cells

Absolute lymphocyte count
<1200
Differentiation of bacterial pneumonia & PCP
Bacterial pneumonia
Pneumocystis pneumonia
Onset:
Acute:
Hours to days
Sub-acute:
days to weeks
Cough:
Productive
Non-productive
Pleuritic chest pain:
Common
Un-common
Shortness of breath:
With chest pain
Prominent on exertion
Common
Very uncommon
Usual
Very uncommon
Often increased
Normal or low
Not helpful
Usually <200/µl
Pleural effusion:
Focal chest Xray infiltrate:
White blood cell count:
CD4 count:
PCP
Bacterial pneumonia
Pneumocystis carinii pneumonia
PCP

Diagnosis
– Frequently clinical
– Typical symptoms
– Response to treatment
– Microscopic demonstration of
P. carinii in lung secretions/tissue
– Culture unavailable
PCP

Diagnosis
– special methods to obtain specimens
are necessary
• Induced sputum/B.A.L./Biopsy

DDX:
– MTB, bacterial pneumonia, fungal
pneumonia, lymphoma, KS
PCP

Treatment
– Trimethoprim-Sulfamethoxazole
– drug of choice (iv 15 mg/kg/day or
oral 2 DS tablets tid)
– 3 weeks recommended
– Allergy to TMP-SMX
– Corticosteroids if severely hypoxic
PCP

Alternative treatment for allergic patients

(all for 21 days)
• pentamidine
• dapsone + trimethoprim
• clindamycin + primaquine
• atovaquone
– less effective
PCP

Prognosis:
– 100% fatal untreated
– Level of hypoxaemia best predicts
outcome

Secondary Prophylaxis
– co-trimoxazole 1-2 tabs daily
– Dapsone 100 mg daily
– aerosilized pentamidine 300 mg monthly
Penicilliosis

Organism:
Penicillium marneffei

Endemic area:
– SE Asia (Northern Thailand, Southern
China, Vietnam, Indonesia, Hong Kong)
– 3rd most common OI in Northern Thailand

CD4 count < 100 cells
Penicilliosis

Clinical symptoms:
– Fever (99%)
– papulo-necrotic skin lesions (71%)
– weight loss (76%)
– anaemia (77%)
– lymphadenopathy (58%)
– hepatomegaly (51%)
– productive cough
– lung disease
Penicilliosis

Diagnosis
– Presumptive:microscopy on
smear
– Definitive: culture
– DDx:
• other disseminated mycobacterial
or
fungal disease
Penicilliosis
Penicilliosis
Penicilliosis

Treatment:
– amphotericin B IV for 6-8 weeks
– amphotericin IV for 2 weeks +
itraconazole 400 mg orally daily
for 10 weeks

In mild cases:
– Itraconazole 400 mg orally daily
for 8 weeks
Penicilliosis

Prognosis:
– high mortality in patients with delayed
diagnosis/treatment.

Secondary prophylaxis
– Itraconazole 200 mg orally daily for life
– > 50% relapse at 1 year without secondary
prophylaxis

Primary prophylaxis - not routinely
indicated
Recurrent Pneumonia

Definition > 1 episode of pneumonia in 12
months

Epidemiology
– common in HIV infected patients
– S. pneumoniae and H. influenzae at least 20
times more common in HIV
– Pneumococcal bacteraemia rate 100 times higher
in AIDS v. non-AIDS

Clinical
– clinical presentation same as for non-HIV
Recurrent Pneumonia
Organism

S. pneumoniae
Stage of HIV Infection

early and late

late
H. influenzae

S. aureus
enteric gram neg rods

M.TB

early and late

Rhodococcus equi

late

Nocardia asteroides

late
Recurrent
Pneumonia
RUL infiltrate caused by Nocardia
RUL infiltrate of TB
TB with cavitation
Disseminated candidiasis
Recurrent Pneumonia

Diagnosis
– clinical evaluation, sputum
smear/culture, CXR, blood culture

Treatment
– as per local guidelines for pneumonia
in non HIV

Prevention
– Co-trimoxazole prophylaxis protects
against recurrent pneumonia
– Improve immune function with
Cryptococcosis
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Clinical features
– fever
– headache
– signs of meningism & photophobia
– malaise, nausea and vomiting
– alteration of mental status
Cryptococcosis
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Diagnosis
– Lumbar puncture - India ink staining
– Cryptococcal antigen, and culture
– Cryptococcal Ag highly sensitive and specific
(CSF and blood)
Titre > 1:8 presumptive evidence of infection

Differential Diagnosis
– pyogenic meningitis, TB meningitis,
toxoplasmosis, neurosyphillis
Encapsulated yeast of Cryptococcus
neoformans in CSF India ink preparation
Cryptococcosis
Cryptococcosis
Cryptococcosis

Treatment of Cryptococcal Meningitis
– Induction phase
• amphotericin B iv daily for 14 days
• consider adding 5-flucytosine (5-FC)
– Consolidation phase
• fluconazole 400 mg po daily for 8 week
Cryptococcosis

Prognosis
– mortality rates as high as 30% despite
therapy

Secondary Prophylaxis
– fluconazole 200-400 mg daily
– itraconazole 100-200 mg po bid (less
effective than fluconazole)
Toxoplasmosis

Organism: Toxoplasma gondii

Epidemiology:
– Cats the definitive hosts
– Ingestion of faecally contaminated
material
– Ingestion of undercooked meat

CD4 count < 100
Toxoplasmosis

Clinical Features:
– encephalitis the most common manifestation
(90%)
• fever (70%), headaches (60%), focal neurological
signs, reduced consciousness (40%), seizures (30%)
• Constellation of fever, headache, and neurological
deficit is classic
– chorio-retinitis
– pneumonitis
– disseminated disease
Toxoplasmosis

Diagnosis
– positive serology with typical
syndrome
– suggestive CT/MRI scan:
• multiple, bilateral cerebral lesions;
hypodense with ring enhancement
– Differential diagnosis
– CNS lymphoma, tuberculoma, fungal
abscess, cryptococcosis, PML
Toxoplasmosis
Toxoplasmosis
Toxoplasmosis- Response to
therapy
Toxoplasmosis

Treatment
– Empirical therapy reasonable as trial,
at least for 2 weeks
– Pyrimethamine plus folinic acid plus
either sulfadiazine or clindamycin
– 6 weeks therapy at least, or until 3
weeks after complete scan resolution
– Corticosteroids for raised intracranial
pressure
Toxoplasmosis

Secondary Prophylaxis
– Essential because latent (cyst) phase
cannot be erdicated
– Pyrimethamine plus folinic acid plus
sulfadiazine (or clindamycin)
– relapse occurs in 20-30% of patients
despite maintenance therapy
– Improve immunity with HAART
Oesophageal Candidiasis

Organism: Candida yeast

CD4 count < 200

Clinical symptoms
– dysphagia, retrosternal pain
– oral thrush in 50-90%
– endoscopy
• ulceration
• plaques
Oesophageal Candidiasis
Oesophogeal Candidiasis

Diagnosis
– oral thrush and dysphagia sufficient
– consider endoscopy if
• symptoms without oral thrush
• failure of empirical antifungal therapy
– Treatment
– Fluconazole 200-400 mg /day until
resolved
– Long term suppressive therapy if recurrent
Mycobacterium Avium Complex (MAC)

Organism: M.avium/M. intracellulare

CD4 count: < 100 cells
Clinical symptoms
– fever & night sweats
– anorexia & weight loss
– Nausea & abdominal pain & diarrhoea
– lymphadenopathy
– hepatosplenomegaly
– anaemia

MAC
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Diagnosis;
– Blood cultures
– 2 blood cultures will detect 95% of cases
– microscopy and culture of bone marrow,
lymph nodes

DDx:
– MTB, disseminated fungal disease,
malignancy
MAC Treatment

Option 1
clarithromycin + ethambutol
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Option 2
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clarithromycin + ethambutol + rifabutin
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Option 3
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HAART
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
MAC
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Prognosis (pre HAART):
– Untreated:
4 months
– Treated:
8 months
Secondary Prophylaxis
– lifelong maintenance required
CMV Disease

Epidemiology:
– a worldwide human herpes virus
– 3 periods of transmission
• perinatal, chidhood, reproductive years
– in LDC’s, > 90% of children infected by 2
yo

CD4 < 50

emerging pathogen in SE Asia?
CMV Retinitis
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Clinical:
– field defects
– floaters
– blurred vision
– rapid deterioration in vision

Diagnosis:
– typical fundoscopic appearance in a
seropositive patient
CMV Retinitis
Toxoplasma Retinitis
Managing CMV retinitis

Treatment
– expensive and toxic
– maintenance therapy essential
– ganciclovir/foscarnet
– IVI or intra-vitreal
– HAART 
CMV Disease

Other clinical manifestations of CMV
– oesophagitis
– colitis
– sclerosing cholangitis
– encephalitis
– polyradiculomyelopathy
– adrenalitis
– pneumonitis
Opportunistic infection prophylaxis in the era
of HAART

Stopping rules
– Fluconazole after CD4 > 100 for 3 months
– Azithromycin after CD4 > 100 for 3
months
– Cotrimoxazole after CD4 > 200 for 3
months

Cessation of secondary prophylaxis more
controversial

Stopping prophylaxis should always be
Opportunistic Infections
Key Points

Very uncommon in those on
successful ARV

Predictable according to CD4 count

Prevention better than cure

Secondary ‘maintenance’ therapy
required

Educate patients