Dr Kirsty Dodgson

Fungal infection in the immunocompromised patient

Aims

• Discuss different types of fungi

• Overview of types of clinical infections

• Clinical Manifestations

Fungus

• Includes – Moulds

• Aspergillus • Fusarium • Dematiaceaous moulds e.g. Exophiala • Mucoraceous moulds e.g. Rhizopus

– Yeasts • Candida • Pneumocystis • Cryptococcus

Epidemiology

• Moulds are everywhere

• We breathe them in constantly

• Soil, vegetation

• Warm moist humid environments

• Neutropenic diet tries to reduce risk

– Crisps

– Pepper

Candida albicans

• Most common species isolated from superficial sites and blood.

• Most pathogenic species.

• Sensitive to most antifungal agents.

Non-albicans Candida species

Many different species, very heterogeneous.

Generally:

• Increasing frequency- multifactorial explanation.

• Probably less pathogenic than C. albicans.

• Often more resistant than C. albicans.

Changing Epidemiology

• ↑ing aggressive therapy, leads to more susceptible patients.

• Ageing population—more susceptible patients

• Use of prophylactic fluconazole leads to decrease in susceptible sp (e.g. albicans) and replacement with resistant sp (e.g. glabrata).

Skin and mucosa

• Asymptomatic colonisation

• Cutaneous candidiasis

• Chronic mucocutaneous candidiasis

• Oesophagitis

• Onychomycosis

• Oropharyngeal candidiasis

• Vulvovaginitis

Oesophagitis

Thrush

• Assocoiated with decrease in normal flora

• Watch for recurrent cases

• If occur perform ID and susceptibilities

Invasive Candidiasis

• Candidaemia

• Intravascular Catheters

• Disseminated candidiasis

Hepatosplenic Candidiasis

• Within the four overlapping forms of invasive candidiasis, there is a distinct clinical picture that has been given a variety of names:

• Chronic Disseminated Candidiasis (CDC)

• Hepatosplenic Candidiasis,

• Hepatic Candidiasis

• and Granulomatous Hepatitis.

• However, the other terms are equally valid.

HS Candidiasis

• Interestingly this is a condition that affects almost exclusively patients undergoing remission induction chemotherapy or bone marrow transplantation for acute leukemia

HS Candidiasis

• Another remarkable aspect of this condition is that it manifests only on recovery from prolonged periods of neutropenia.

• The other near constant finding is one of a group of abdominal symptoms.

• Right upper quadrant tenderness, hepatomegaly, abdominal distension, nausea, vomiting and diarrhoea occur with variable frequency.

HS Candidiasis

• Liver Function Tests. One of the most consistent biochemical findings in hepatosplenic candidiasis is a marked elevation on serum alkaline phosphatase.

• White Blood Count. Another commonly reported finding among patients with CDC is rebound leukocytosis

• Unfortunately, these laboratory changes are very similar to those found in cases of GVHD and sepsis-related cholestatic liver disease, thus confusing the diagnosis

Deep Organ Candidiasis

• Abdomen (Peritonitis)

– Peritoneal Dialysis-related Candida Peritonitis – Gut-injury Related Candida Peritonitis

• Bone & Joint Candidiasis

– Candida Osteomyelitis

Candida Arthritis

• Brain & Nerves (CNS candidiasis)

– Neurosurgery-related CNS candidiasis

• Eye (Endophthalmitis) Gallbladder (Biliary Candidiasis) Heart (Cardiac Candidiasis) Lung (Candida Pneumonia) Kidney & Bladder (Urinary Candidiasis)

– Fungus Balls in Urinary Tract Asymptomatic Funguria

• Liver & Spleen (Hepatosplenic Candidiasis) • Pancreas (Pancreatic Candidiasis)

Pneumocystis Jiroveci Pneumonia

• Normal flora in healthy competent individuals

• Normally seen as a reactivation in immunocompromised patients

• Traditionally an AIDS defining illness but seen in any immunocompromised pt

• Haematology, oncology and solid organ transplant pts

• Previously Pneumocystis carinii (PCP)

PJP

• Main symptom, exertional dyspnoea

• Marked desaturation

• Its actually a fungus

• Send deep samples for PJP PCR

• Sputum not ideal but better than nothing

• BAL is the gold standard

PJP

PJP Rx

• Treat with Septrin HD • Atovaquone suspension - However, oral atovaquone

has limited and unpredictable bioavailability • Dapsone with trimethoprim - dapsone is given

intravenously or occasionally in nebulised form in the treatment of PCP.

• Clindamycin with primaquine (unlicensed use in the UK)

• Aerosolised pentamidine isetionate is no longer recommended because it is associated with increased frequency of relapse

• Must receive 21 days total treatment

Crytococcus

• Characteristic features:

• Yeast

• forms capsule (seen on india ink stain)

Cryptococcus neoformans

Cryptococcus

• 34 species in the genus

• C. neoformans only one of real importance though case reports of other sp causing disease.

• 2 varieties exist: C. neoformans var neoformans and var gattii

Cryptococcus

var neoformans

• found worldwide

• pigeon droppings

• soil

• Serotypes A, D & AD

var gattii

• Tropical and subtropical

• eucalyptus trees

• Serotypes B & C

Cryptococcus

Disease

Organism inhaled-usually no or mild symptoms. pneumonia rare even in immunocompromised

Meningitis-strongly neurotropic often subacute onset in immunocompetent

Immunocompromised-HIV, transplant

Cryptococcus

Diagnosis

• Microscopy of CSF

• Culture-CSF, Blood

• Anitgen-Blood, CSF

Aspergillus

• Most common mould infection but not all mould infections are aspergillus

• Diagnostics are poor so clinical diagnosis is key

• Fungi are angioinvasive so blood/sputum are rarely positive even by PCR

• Consider B-Glucan and galactomannan based on local policy

Aspergillus

Gram Stain

Sites of Infection

Categories Sites Involved

Colonization Sinuses, lungs

Allergic bronchopulmonary aspergillosis Sinuses, lungs

Pulmonary aspergilloma Pre-existing lung cavity

Invasive aspergillosis

- Pulmonary aspergillosis 1

- CNS aspergillosis - Sinonasal aspergillosis - Osteomyelitis - Endophthalmitis - Endocarditis - Renal abscesses - Cutaneous

Others

- Cutaneous: burns, post surgical wounds, IV insertion sites, etc. - Otomycosis - Exogenous endophthalmitis - Allergic fungal sinusitis - Urinary tract fungus balls

1This is the most common site of primary invasive aspergillosis.

Aspergilloma

• Colonise pre-existing cavities

• May be excised as can erode through and cause haemoptysis

Invasive Apergillosis

Invasive Apergillosis

18 mo girl with leukaemia

Other Moulds

• Zygomycetes

– Causes mucormyosis

– Rhinocerebral mucor, high mortality

• Fusarium

– Disseminated infection

THE

END