Epidemiology and ecology of fungal diseases

Epidemiology and ecology of fungal diseases

Healthcare Focus on: - individual - diagnosis - treatment Public Health Focus on: - population - prevention

The nature of fungi Kingdom Fungi (lat. fungus, -i) Diverse group of eukaryotic organisms - all must lead heterotrophic exsistance in nature as parasites or saprobes, dependent on living or dead organic matter for their nutrition Among more than 250 000 species of fungi that have been described, 200 have been associated with human disease In general these organisms are free-living in nature and are in no way dependent of humans (or animals) for their survival Fungal cells are similar to animal cells but are characterized by the presence of a polysaccharide-based cell wall

Types of fungi There are two principal types of fungi: I. The yeasts single cells which reproduce by a process of bud formation to give rise to single daughter cells (unicellular organisms Candida) II. The mycelial or mould fungi form chains of contiguous cells, hyphe (filamentous fungi) (multicellular organisms Aspergillus) Dimorphic fungi exist as either yeasts or mycelia at different stages of their life cycles (Histoplasma)

Mycoses Fungi can cause human disease in a number of different ways, through the production of toxins, sensitizing antigens (allergens) or by the invasion of tissue Invasive diseases caused by fungi are known collectively as the mycoses (fungal infections) medical mycology The fungi are recognized causes of disease in all parts of the world The distribution of mycoses is affected by a number of factors: the presence of the organisms in the environment, host immunity, frequency and route of exposure and the use of invasive or immunosuppressive medical technology

Mycoses - classification Superficial (including cutaneous) Subcutaneous Invasive (systemic, deep) Endogenous Exogenous Fungal pathogens a. true pathogens (dermatophytes, dimorphic fungi) b. opportunists (Candida, Aspergillus)

Superficial mycoses Infections limited to the outermost layers of the skin, the nails and hair, and the mucous membranes Dermatophytoses (ringworm) and superficial forms of candidosis Many of these infections are mild and readily diagnosed, and respond well to treatment

Subcutaneous mycoses Infections involving the dermis, subcutaneous tissues and bone Infections are usually acquired as a result of the traumatic implantation of organisms that grow as saprobes in soil and decomposing vegetation Most frequent in rural populations of the tropical and subtropical regions, where individuals go barefoot and wear minimum of clothing Mycetoma Madurella etc.

Invasive mycosis Infections that usually originate in the lungs, but may spread to many other organs Agents: the true pathogens and the opportunists

Invasive mycoses caused by true pathogens Endemic mycoses Fungi geographically restricted to specific geographic areas Pathogens are living in soil, bird droppings and air Agents: a. Histoplasma capsulatum b. Coccidioides immitis c. Blastomyces dermatitidis d. Paracoccidioides brasiliensis. They cause pneumonia and systemic disease in a previously healthy persons

Invasive infections caused by opportunists Endogenous - means that the fungus is a part of a normal human flora a. Candida b. Pneumocystic jiroveci (previously known as P. carinii) - most probably a part of normal flora of the lungs of many mammals, including humans.exogenous - means that the fungus does not normaly live in/on human body, although it can transiently contaminate human body surfaces (especially respiratory tract) a. Cryptococcus neoformans b. Aspergillus

Opportunistic mycoses Occur in individuals who are debilitated or immunosuppressed as a result of an underlying disease or their treatment In most cases, infection results in significant disease Resolution of the infection does not confer protection, and reinfection or reactivation may occur if host resistance is again lowered Many of the organisms involved are ubiquitous saprobes, found in the soil, on plants and decomposing organic matter and in the air

High risk patient opportunistic mycoses Neutropenia Immunosuppression a. HIV, transplantation Community b. premature acquired c. diabetic. ICU Hospital acquired a. trauma, burn b. septic shock. Abdominal surgery. Prolonged antibiotic tratment

Hematology Agent Candida Aspergillus Mucorales, Fusarium, Scedosporium Unknown Cryptococcus Dimorphic Pneumocystis Incidence Decrease: 70 42% 13 29% 4-12% 6% 4% 3% 2%

Candidosis Although candidiasis is endogenous in most cases, cross infections are described, especially in intensive care unit patients Handwashing is the most important activity to prevent spread of many hospital pathogens, and of Candida too

Estimated annual cases of HIV-associated cryptococcosis Eastern Europe Western & Central Europe & Central Asia North America 7,800 Caribbean 7,800 Latin America 54,400 27,200 500 East Asia North Africa & Middle East 6,500 Sub-Saharan Africa 720,000 13,600 South & South-East Asia 120,000 Oceania 100 Global total: 957,900 cases (range: 371,700 1,544,000) Park et al. AIDS 2009; 23: 525-30

Aspergillosis Invasive aspergillosis in the ICU High - risk category Neutropenia (neutrophil count, <500 neutrophils/mm³) Hematological malignancy Allogenic bone marrow transplantation Intermediate - risk category Prolonged treatment with corticosteroids before admission to the ICU Autologous bone marrow transplantation Chronic obstructive pulmonary disease Low risk category Severe burns Other solid-organ transplant recipients (heart,

Sources of Aspergillus Environment Food long list! sharing of salt and pepper pots Standing water Ice-making machines Fomites carpets/furniture/fabrics/soft toys

Patients live in mouldy houses: exposure to Aspergillus and more

Patients live in mouldy houses and are exposed to Aspergillus

Prevention is better than cure! Avoid exposure in the hospital and in the home

The majority of IFIs are identified post-mortem Pre-mortem Post-mortem 33% How can we better identify patients with IFIs during life? 12.3% * Only ¼ diagnosed pre-mortem *Incidence of moulds and yeasts in AML patients (7.9% due to moulds). Prevalence of invasive moulds and Candida (22% due to moulds). 1. Pagano L et al. Haematologica. 2006;91:1068-1075. 2. Chamilos G et al. Haematologica. 2006;91:986-989.

Opportunistic fungal infections are difficult to diagnose difficult to treat difficult to prevent more and more frequent (emerging diseases) a great challenge for a future work in all fields