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Introduction to the diagnosis and
management of common opportunistic
infections (Ols)
Module 4 Sub module OIs
Opportunistic Infections
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)
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
Clinical features
– fever
– headache
– signs of meningism & photophobia
– malaise, nausea and vomiting
– alteration of mental status
Cryptococcosis
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
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
Option 2
clarithromycin + ethambutol + rifabutin
Option 3
HAART
MAC
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
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