No abstract

For a long time, the diagnostic approach to IA/Aspergillus disease has been a challenge. The definitive diagnosis is made by correct microbiological and/or histopathological documentation, undoubtedly the fundamental cornerstone for therapeutic decision-making. However, it is considered limited by lack of sensitivity and speed, often being counterproductive, as in many cases invasive procedures are needed (e.g., fibrobronchoscopy [FBC] or tissue biopsy), which delays treatment and undermines survival of at-risk patients. This highlights the need for faster and more accurate diagnostic tools. Although novel serological and molecular methods have been developed that have demonstrated their potential to replace conventional diagnostic tests, inconsistencies in interpretation and validation among the different approaches limit their reproducibility and large-scale clinical application. However, whenever possible, an immunological and/or molecular diagnosis should be made, as it has proven useful in different detection and diagnostic strategies, which with an understanding of its strengths and limitations, and the standardization of the different techniques available, can be incorporated into care protocols and diagnostic algorithms, as an aid in administering and monitoring the different antifungal treatments and predicting possible clinical outcomes. Due to the limited sensitivity (SE) of many of the tests, and variations in the specificity (SP) of some of them, the combined use of several diagnostic tools during the high-risk period for invasive infection and/or during the early period in the course of IA/Aspergillus disease would allow an adequate diagnostic approach, provided that their results are interpreted together with the existing clinical and imaging information.

Despite the ubiquity of Aspergillus species, and the fact that a person may inhale hundreds of conidia daily, only a small proportion of patients develop an infectious disease. Aspergillus spp. can cause a wide spectrum of diseases, depending on the patient’s underlying immune function; these range from an allergic syndrome, (which does not represent a true infection), a hypersensitivity reaction (ABPA), a chronic process (CPA) or invasive aspergillosis (IA). All diseases associated with Aspergillus spp. have the potential to be misdiagnosed because symptoms and/or clinical findings overlap with each other, or with other non-fungal conditions. Greater clinical recognition of the different pulmonary syndromes is needed to identify those patients who could benefit from an appropriate therapeutic approach. Multidisciplinary management is required, where the role of antifungal therapy is only established for symptomatic and/or progressive disease management, taking into account the potential for azole resistance, which adds to the complexity of treatment and, in some cases, limits therapeutic options.

The invasive aspergillosis (IA) continues to be an important cause of morbidity and mortality, difficult to manage in severely immunocompromised patients, however, with its appearance in a heterogeneous group of patients (e.g., critical ICU patients, patients with human immunodeficiency virus [HIV/AIDS], etc.), who were not classically considered high risk, as well as more chronic forms of aspergillosis, (including those with a propensity for invasion), which have been better defined, different antifungal treatment modalities have been established for Aspergillus-associated infections according to the specific patient’s condition. The understanding of the different risk factors for the development of IFI/IA, which are constantly evolving, and which include, among others, the underlying malignancy, the associated condition and treatment, the presence of comorbidities, environmental exposure, and the presence of certain genetic polymorphisms in the patient, allows for a more precise risk stratification, which together with the use of diagnostic algorithms, would allow the characterization of patients who would benefit from the different early intervention strategies, and the optimization of management protocols. The evaluation of the clinical manifestations of the patient is an essential step, as it involves the site of infection, the severity and dynamic nature of immunosuppression, and the characteristics of the etiological agent involved, which with the use of imaging modalities (with an increasingly important role in diagnosis), and of novel and accessible diagnostic tools, useful for the detection and follow-up of the disease, allow the early recognition of the infection, the selection of an early antifungal treatment, the use of more effective antifungal drugs and the development of local clinical practice guidelines

The clinical manifestations of Aspergillus spp. associated diseases are variable and depend on the interaction between the inoculating dose (which is not known and probably varies widely), the patient’s ability to resist infection at both local and systemic level, and the virulence of the etiologic agent. The major difficulty in establishing a clinical classification scheme lies in the existence of a broad and continuous spectrum of disease, associated with a complicated diagnosis and clinical management. An IA can present as a localized infection in one organ, or as part of a disseminated infection, which presents itself in a varied spectrum of clinical pictures. However, no clinical trials have been completed to evaluate the different specific therapeutic approaches according to the type of involvement in these patients. The most common clinical forms of invasive aspergillosis (IA) occur in the lung and paranasal sinuses, chronic pulmonary aspergillosis (CPA) can be complicated by spreading to contiguous structures such as the pleural space, pericardium, chest wall and mediastinal structures such as the esophagus and great vessels. It frequently spreads beyond the respiratory tract, and can affect the skin, CNS, eyes, liver, kidneys and other structures.