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 900 800 700 600 500 400 300 200 100

50 <50

0

PCP Cryptococcal meningitis PPE

CD4 COUNT

0 3 6 9 1 2 3 4 5 6 7 8 9 10 Months Years

TB

Oral candida OHL

HZV

CMV MAC

TB

TB

TB

Cryptosporidial diarrhea

Common opportunistic infections

The most common opportunistic infections

0 5000 10000 15000 20000 25000

Pneumonia, recurrent

Candidiasis, oesophageal

Cryptococcosis

PCP

Tuberculosis

Division Epidemiology, Department of Communicable Diseases Control, MOPH, Thailand

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

Pleural effusion: Common Very uncommon

Focal chest Xray infiltrate: Usual Very uncommon

White blood cell count: Often increased Normal or low

CD4 count: Not helpful Usually <200/µl

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 outco

me

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 pr

ophylaxis

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

H. influenzae

S. aureus

enteric gram neg rods

M.TB

Rhodococcus equi

Nocardia asteroides

Stage of HIV Infection

early and late

late

early and late

late

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 HAART

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 contr

oversial

Stopping prophylaxis should always be done by

trained HCW on a case per case basis

Opportunistic Infections Key Points

Very uncommon in those on successful AR

V

Predictable according to CD4 count

Prevention better than cure

Secondary ‘maintenance’ therapy required

Educate patients