Professional article Zdrav Vestn | januar – februar 2017 | Letnik 86 Microbiology and immunology PROFESSIONAL ARTICLE Fungal infections in patients with cystic fibrosis Glivne okužbe pri bolnikih s cistično fibrozo Rok Tomazin, Tadeja Matos Abstract Institute of Microbiology In the last two decades prevalence of fungal infections is increasing for various reasons. One of them and Immunology, Faculty is the advance of medical science and the associated longer life expectancy in some patient groups. of Medicine, University of This includes cystic fibrosis patients who encounter fungal diseases already in their childhood. Fun- Ljubljana, Slovenia gal pathogens isolated in high frequencies from the respiratory tract include Aspergillus fumigatus, Korespondenca/ Candida albicans and Scedosporium apiospermum. In the case of cystic fibrosis, these organisms Correspondence: normaly colonise the respiratory and intestinal mucosae and can cause hipersensitivity reactions Rok Tomazin, and invasive diseases. The fungus-patient interactions are complex and depend on several different e: [email protected] factors which determine what course will the colonisation/infection take. lj.si Ključne besede: Izvleček cistična fibroza; glivne V zadnjem času se pojavnost glivnih okužb povečuje iz različnih razlogov. Eden od njih je napredek okužbe; Aspergillus; v medicinski znanosti in z njim povezana daljša pričakovana življenjska doba določenih skupin bol- Candida; Scedosporium nikov. Sem spadajo tudi bolniki s cistično fibrozo, ki se s problematiko glivnih patogenov srečujejo Key words: že v otroštvu. Največjo vlogo imajo glive Aspergillus fumigatus, Candida albicans in Scedosporium cystic fibrosis; fungal apiospermum. Pri cistični fibrozi so ti organizmi kolonizatorji dihal in prebavil, povzročitelji pre- infections; Aspergillus; občutljivostnih reakcij in v redkih primerih povzročitelji invazivnih okužb. Do kakšnega poteka bo Candida; Scedosporium prišlo, je odvisno od značilnosti posameznega bolnika, glive in okolja ter izredno kompleksnih inte- rakcij med njimi. Citirajte kot/Cite as: Zdrav Vestn. 2017; 86(1–2):42–52 Received: 18. 5. 2016 Cystic fibrosis and fungi Accepted: 7. 12. 2016 Cystic fibrosis (CF) is one of the most in the transport of ions on the respira- common autosomal recessive genetic tory epithelium and the resulting change diseases. One in every twenty-seven in viscosity of the secretions hinder the people carries a recessive allele. The dis- functioning of the mucociliary escala- ease occurs as the result of mutations in tor which creates favourable conditions the CFTR gene (Cystic Fibrosis Trans- for the development of various infec- membrane Conductance Regulator), tions. They are most frequently caused which affects the irregular synthesis of by Staphylococcus aureus, Haemophi- the protein involved in the transport of lus influenzae, Burkholderia cepacia and chloride ions across the membrane of Pseudomonas aeruginosa. The latter is the epithelial cells. Consequently, many considered one of the main causes for organ systems are affected, especially the progressive reduction in pulmonary the respiratory tract (1). Disturbances functions in many CF patients (1,2). In Fungal infections in patients with cystic fibrosis 1 MICROBIOLOGY AND IMMUNOLOGY recent times, more interest has been paid and Rasamsonia argillacea, whose role in to infections caused by opportunistic CF pathobiology has yet to be defined. pathogenic fungi. Fungi are ubiquitous eukaryotic or- Fungi of the genus Candida ganisms, which may colonise the respir- atory and digestive tracts and causehy- Species of the genus Candida are as- persensitivity reactions and infections in comycetous yeasts, which can normally CF patients (3). The most common types be found in the oral and intestinal mu- of fungi isolated in CF patients include cosa, moist areas of the skin, the upper Aspergillus fumigatus, Candida albicans respiratory tract and genital mucosa. and Scedosporium apiospermum (3). They are present in people with a normal Initially, disorders or weakening of the immune response, as well as in patients immune system are not typical for CF with immunodeficiencies. Table 1 sum- patients, therefore the localisation of marises interactions between candida fungi is limited to the respiratory epithe- and a CF patient. lium. Irregular mucus secretion from the Factors associated with the isolation lower respiratory tract causes long-term of yeasts or candida include pancreatic exposure to fungal antigens, which leads insufficiency, osteopenia, diabetes mel- to the development of hypersensitivity litus and the concurrent colonisation reactions. Consequently, chronic coloni- with the bacteria P. aeruginosa (4,5). The sation and hypersensitive reactions are high proportion of CF patients colo- the main types of relationship between nised with candida (49.4 %) is mainly fungi and a CF patient. In immunosup- due to the progression of the underlying presed state, which normally occurs af- disease (6). The most frequently isolated ter lung transplantation, the relationship species is C. albicans, followed by Can- between opportunistic pathogens and dida glabrata, Candida parapsilosis, Can- the patient can become more severe. In dida krusei and Candida tropicalis. They such cases, though very rare in CF pa- are often recovered from the sputum, but tients, fungi can invade the lung paren- the clinical significance of these isolates chyma and cause an invasive pulmonary is questionable because of the natural mycosis, which, in the absence of an im- occurrence of yeasts in the oral cavity mune response, can progress into multi- and pharynx; there is no proof support- organ disseminated infection associated ing the efficiency of antifungal treatment with high mortality. in these cases (7,8). In certain situations, the commensal Clinical mycology in relationship in CF patients turns into cystic fibrosis parasitism. The most commonly en- countered are superficial infections that Every day, CF patients are exposed affect the oral and/or genital mucosa. to an environment inhabited by fungi, There have been documented cases of including moulds and yeasts. A wide oropharyngeal candidosis, the develop- variety of fungi can be isolated from ment of which is enhanced by the im- respiratory samples but the two most paired functioning of the salivary glands, documented and studied agents are A. CF-related diabetes, steroid treatment fumigatus and C. albicans. Other com- and broad-spectrum antibiotic treat- mon and interesting isolates include S. ment (6). Since there may also be other apiospermum, Exophiala dermatitidis causes for a similar symptomatology in 2 Zdrav Vestn | januar – februar 2017 | Letnik 86 PROFESSIONAL ARTICLE CF patients (e.g. vitamin B complex de- ops into sepsis is associated with a high ficiency), microbiological confirmation mortality rate ranging between 30 and is always advised (6). Female CF patients 60 % (13). In order to monitor the pro- often suffer from fungal vulvovaginitis; gression of candidaemia and determine its occurrence is probably underesti- the damage to the organs, a fundoscopy mated as very little attention is paid to and a transoesophageal echocardiog- this type of fungal infections in CF (9). raphy are advised for neutropenic pa- Most superficial candidoses are success- tients (14). The first choice for treatment fully treated with fluconazole, while se- are antifungals from the group of echi- rious cases and chronic recurrences of nocandins, usually caspofungin (10,11). the infection are treated with itracona- The choice of antifungal medication de- zole (10,11). pends on the type of pathogen and the In addition to the aforementioned su- site of infection, among other factors. perficial infections, Candida spp. can also cause candidaemia and invasive can- Fungi of the genus Aspergillus didosis, which can develop into septic shock if not treated properly. The origin Species of the genus Aspergillus are of the infection is usually endogenous ubiquitous filamentous ascomycete fun- – candida are part of the normal gastro- gi. They are found in the air, water, dust intestinal microbiota. The origin of the and decomposing plants. Respiratory in- infection can also be the various vascu- fection or colonisation occurs through lar catheters on which yeasts form bio- the inhalation of aerosolised conidia. films. Lung transplant patients who re- The latter are small enough (2–5 µm) ceive immunosuppressives after surgery to enter the lower respiratory tract, but are at particularly high risk for invasive in a healthy person they are expelled candidosis (5,6). The haematogenous regularly by the clearance and defensive dissemination of candida mainly affects functions of the respiratory epithelium. the kidneys, spleen, skin, eyes, heart and In CF patients these two functions are meninges (12). Candidaemia that devel- compromised, therefore various types of Table 1: Summary of the roles of different species of the genusCandida in CF patients. Infection, Colonisation Surface infection Systemic infections colonisation with Candida spp. Risk factors in CF Diabetes, Diabetes, Immunosuppression after osteopenia, treatment with corticosteroids, transplant colonisation with treatment with broad-spectrum surgery Pseudomonas aeruginosa antibiotics Clinical significance Short-term: Candidosis of the oral cavity and Candidaemia, / pharynx, disseminated candidosis, Long-term: fungal vulvovaginitis invasive candidosis progression of the underlying disease Medication of