XÂY DỰNG MÔ HÌNH PHÂN TÍCH CHI PHÍ – HIỆU QUẢ ISAVUCONAZOLE TRONG ĐIỀU TRỊ NHIỄM NẤM ASPERGILLUS XÂM LẤN TẠI VIỆT NAM

Nhiễm nấm Aspergillus xâm lấn (Invasive Aspergillosis – IA) là một thể bệnh nặng trong các thể nhiễm nấm Aspergillus, rất thường gặp ở người bệnh suy giảm miễn dịch. Thuốc isavuconazole (ISA) ra đời nhằm thay thế các liệu pháp khác trong điều trị IA với hiệu quả lâm sàng vượt trội đã được chứng minh trong các thử nghiệm lâm sàng. Với phương pháp mô hình hóa kết hợp tổng quan tài liệu và tham vấn ý kiến các chuyên gia lâm sàng, nghiên cứu đã xây dựng được mô hình phân tích CP-HQ trong điều trị IA tại Việt Nam bằng phần mềm Microsoft Excel với cấu trúc mô hình bao gồm 2 phương án lựa chọn điều trị với các thông số đầu vào (xác suất, chi phí, hiệu quả) từ đó ước lượng được các thông số đầu ra (chỉ số gia tăng CP-HQ và độ nhạy của mô hình). Mô hình xây dựng cho phép phân tích CP-HQ của 2 phác đồ và có thể đưa ra kết luận về hiệu quả kinh tế của liệu pháp điều trị hiệu quả tối ưu với chi phí tối thiểu trong điều trị IA.

Fungal Infections Other Than Invasive Aspergillosis in COVID-19 Patients

Invasive fungal disease (IFD) associated with Coronavirus Disease 2019 (COVID-19) has focussed predominantly on invasive pulmonary aspergillosis. However, increasingly emergent are non-Aspergillus fungal infections including candidiasis, mucormycosis, pneumocystosis, cryptococcosis, and endemic mycoses. These infections are associated with poor outcomes, and their management is challenged by delayed diagnosis due to similarities of presentation to aspergillosis or to non-specific features in already critically ill patients. There has been a variability in the incidence of different IFDs often related to heterogeneity in patient populations, diagnostic protocols, and definitions used to classify IFD. Here, we summarise and address knowledge gaps related to the epidemiology, risks, diagnosis, and management of COVID-19-associated fungal infections other than aspergillosis.

Two Monoclonal Antibodies That Specifically Recognize Aspergillus Cell Wall Antigens and Can Detect Circulating Antigens in Infected Mice

Invasive aspergillosis (IA) is a life-threatening disease mainly caused by Aspergillus fumigatus and Aspergillus flavus. Early diagnosis of this condition is crucial for patient treatment and survival. As current diagnostic techniques for IA lack sufficient accuracy, we have raised two monoclonal antibodies (1D2 and 4E4) against A. fumigatus cell wall fragments that may provide a platform for a new diagnostic approach. The immunoreactivity of these antibodies was tested by immunofluorescence and ELISA against various Aspergillus and Candida species in vitro and by immunohistochemistry in A. fumigatus infected mouse tissues. Both monoclonal antibodies (mAbs) showed intensive fluorescence with the hyphae wall of A. fumigatus and A. flavus, but there was no staining with other Aspergillus species or Candida species. Both mAbs also showed strong immunoreactivity to the cell wall of A. fumigatus hyphae in the infected liver, spleen and kidney of mice with IA. The antigens identified by 1D2 and 4E4 might be glycoproteins and the epitopes are most likely a protein or peptide rather than a carbohydrate. An antibody-based antigen capture ELISA detected the extracellular antigens released by A. fumigatus, A. flavus, A. niger and A. terreus, but not in Candida species. The antigen could be detected in the plasma of mice after 48 h of infection by double-sandwich ELISA. In conclusion, both 1D2 and 4E4 mAbs are potentially promising diagnostic tools to investigate invasive aspergillosis.

Invasive aspergillosis a complication severe respiratory viral infections (influenza and COVID-19)

Invasive aspergillosis is a life-threatening complication in patients with severe influenza and COVID-19 in intensive care units. Risk factors for the invasive aspergillosis development are transitory immunosuppression associated with severe influenza and COVID-19, as well as the use of glucocorticosteroids and immunosuppressive therapy. In the presence of risk factors, suspected clinical and radiological signs of invasive aspergillosis, bronchoscopy and examination of material from the lower respiratory tract are necessary: test for galactomannan, microscopy with white calcofluor staining and inoculation on Sabouraud agar medium. Voriconazole or are recommended as first-line treatment for invasive aspergillosis in patients with severe influenza and COVID-19. Amphotericin B Liposomal, Amphotericin B Lipid Complex, and Caspofungin are the alternative options for the invasive aspergillosis treatment. Combination therapy is possible. It is necessary to control the underlying disease with eliminate or reduce the severity of risk factors.

Clinical and Epidemiological Profile of Patients with Invasive Aspergillosis from a Fourth Level Hospital in Bogota, Colombia: A Retrospective Study

Invasive aspergillosis (IA) is a severe mycosis caused by Aspergillus species. The infection mainly affects immunocompromised patients with a significant clinical burden. This study aimed to determine the clinical and epidemiological characteristics of patients diagnosed with IA in a fourth level hospital in Colombia, as these data are scarce in the country. A retrospective, observational study, from a single center was conducted with 34 male and 32 female patients, between 1 month- and 90-year-old, diagnosed with proven (18.2%), probable (74.2%) and possible (7.6%) IA, during a 21-year period. The most frequent underlying conditions for IA were chemotherapy (39.4%) and corticosteroid use (34.8%). The lung was the most common affected organ (92.4%). Computed tomography (CT) imaging findings were mainly nodules (57.6%) and consolidation (31.8%). A low positive correlation was found between serum galactomannan and hospitalization length. Aspergillus fumigatus prevailed (73.3%) in sputum and bronchoalveolar lavage cultures. Most patients were hospitalized in general wards (63.6%) and treated with voriconazole (80.3%). Mortality rate was 15.2%. Common risk factors for IA were identified in the Colombian cohort, including medications and underlying diseases. However, their frequency differs from other countries, reinforcing the idea that local surveillance is essential and at-risk patients should be carefully monitored.

Dynamic optimization reveals alveolar epithelial cells as key mediators of host defense in invasive aspergillosis

Aspergillus fumigatus is an important human fungal pathogen and its conidia are constantly inhaled by humans. In immunocompromised individuals, conidia can grow out as hyphae that damage lung epithelium. The resulting invasive aspergillosis is associated with devastating mortality rates. Since infection is a race between the innate immune system and the outgrowth of A. fumigatus conidia, we use dynamic optimization to obtain insight into the recruitment and depletion of alveolar macrophages and neutrophils. Using this model, we obtain key insights into major determinants of infection outcome on host and pathogen side. On the pathogen side, we predict in silico and confirm in vitro that germination speed is an important virulence trait of fungal pathogens due to the vulnerability of conidia against host defense. On the host side, we found that epithelial cells, which have been underappreciated, play a role in fungal clearance and are potent mediators of cytokine release. Both predictions were confirmed by in vitro experiments on established cell lines as well as primary lung cells. Further, our model affirms the importance of neutrophils in invasive aspergillosis and underlines that the role of macrophages remains elusive. We expect that our model will contribute to improvement of treatment protocols by focusing on the critical components of immune response to fungi but also fungal virulence traits.