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摘要
Fungal infections are becoming increasingly frequent, with Aspergillus and Candida infections occurring most often. This article reviews the different patient groups that are susceptible to fungal infections and the techniques for identifying the causative agents. Also considered are the changing trends in the incidence of fungal infections and the spectrum of fungal species.
All patients with a compromised immune system are at risk of developing fungal infections. Hospitilization itself increases the risk of fungal infections in immunocompromised patients, for example through measures such as prolonged catheterization.
Neutropenia due to underlying hematological malignancy or induced by chemotherapy is an important risk factor for the development of fungal infections. The most frequent causative agents are Candida albicans and Aspergillus fumigatus. Fungal infections in this patient group are a major cause of morbidity and mortality and prevention is therefore critical.
Bone marrow transplant patients are at increased risk, with invasive Aspergillus infection being the leading cause of death in this group. Solid-organ transplantation also carries an increased risk of infection because of the use of immunosuppressive therapy to limit the risk of rejection, Each type of solid-organ transplant brings its own particular risk factors. Although the majority of fungal infections in this group are caused by Candida and Aspergillus species, emerging opportunistic fungal pathogens, such as Histoplasma and Cryptococcus species are also on the increase.
People infected with HIV are particularly susceptible to virulent and persistent fungal disease. Cryptococcus neoformans, Histoplasma, Penicillium marneffei and Coccidioides are the most frequently observed pathogens. In addition, superficial Candida infections may affect up to 95% of the HIV-positive population. Pneumocystis carinii, now classified as a fungus will not be considered in this review.
Other high-risk groups include bums patients, those with lung disease and those undergoing surgical procedures, particularly to the gastrointestinal tract. Patients treated in intensive care units also have high rates of nosocomial infections, most frequently caused by Candida species. In addition, a number of rare congenital defects, such as chronic granulomatous disease, can lead to increased susceptibility to fungal disease.
Early diagnosis of the pathogenic species is important as this can guide initial treatment. Traditionally, most information on fungal pathogens has been obtained from culture and microscopic analysis of samples taken from autopsies, but advances in molecular biology have resulted in a number of new techniques for identifying infecting species. Restriction fragment length polymorphism analysis has been used successfully to differentiate non-albicans Candida species, although the results can often be difficult to interpret. DNA hybridization analysis produces clearer banding patterns than restriction enzyme analysis, but the technique is often too time-consuming for patients in need of urgent treatment. Electrophoretic karyotyping is one of the better molecular procedures for differentiating between genetically related Candida species, but is also time-consuming and can have variable results.
Two popular techniques that offer great potential for precision, sensitivity and speed of molecular typing are random amplification of polymorphic DNA and polymerase chain reaction fingerprinting. To date, however, these technologies are limited to research laboratories. Another promising technique is the use of microsatellite markers to distinguish different pathogenic strains. Although expensive and time-consuming, the technique is reliable and enables results to be obtained with small or degraded amounts of DNA.
Although Candida and Aspergillus continue to be the cause of most systemic fungal infections, surveillance of fungal pathogens has identified some changing epidemiological trends. Monitoring on a national scale has revealed a steadily increasing prevalence of fungal infections over the past few decades in addition to a change in the type of infections seen. For example, a substantial shift in the epidemiology of Candida species has taken place recently, leading to an increase in non-albicans species. These species cause infections with higher complication and death rates than those resulting from C. albicans. Most worrying is the emergence of C. krusei, which is resistant to many antifungal agents.
Although still rare, endemic diseases such as histoplasmosis and blastomycosis are also increasing in areas not normally associated with these diseases. This has resulted partly from more frequent global dispersal of fungi caused by increased travel and other risk factors. In addition, because of the increase in immunocompromised individuals resulting from the emergence of HIV and the use of chemotherapy and other medical interventions, new opportunistic fungi are now causing significant problems.
In conclusion, many factors can increase the risk of developing fungal infection, and minimizing these risks, wherever possible, will reduce the burden of disease. New drugs or new formulations of old drugs could improve the prognosis of patients at highest risk of developing fungal infections.
- 出版日期2002-12
