Incidence Of Invasive Aspergillosis Research Articles

A Perspective Study on Therapeutic Drug Monitoring of Voriconazole in Pediatric Patients with Hematologic Disorders

Background: The incidence of invasive aspergillosis and the administration of voriconazole have risen among immunocompromised patients. Objectives: This study aimed to evaluate serum voriconazole concentration and its corresponding influential factors in pediatric patients with hematologic disorders. Methods: A total of 132 blood samples were collected from 44 pediatric patients with hematologic disorders infected with invasive aspergillosis and treated with voriconazole. Among these patients, 20.5% were classified as having proven invasive aspergillosis, 77.2% as probable, and 2.3% as possible. Voriconazole serum levels were evaluated using HPLC on the 3rd, 5th, and 7th days of treatment. Genotyping of the CYP2C19 alleles (*2, *3, and *17) was performed, and demographic and clinical data were gathered from records between 2018 to 2020. Results: The voriconazole concentration in 70.5% of patients and 77.3% of treatment cases (complete or partial) ranged from 1 to 5.5 µg/mL. Adverse events were observed in 4.5% of the patients. Genotyping of CYP2C19 genes revealed CYP2C1911 (5.4%), CYP2C19117 (16.2%), CYP2C1912 (51.4%), and CYP2C19217 (27%). Multivariate analysis using linear regression demonstrated that serum voriconazole concentration increased by 0.037 µg/mL per year of age and by 0.06 µg/mL for each unit increase in C-reactive protein (on the 3rd day of voriconazole therapy). Additionally, an increase in alanine aminotransferase level by 1 unit decreased the mean voriconazole concentration by 0.03 µg/mL. Of these patients, 65.9% were completely treated, 11.4% were partially treated, and 22.7% died. Conclusions: Serum voriconazole concentrations varied among pediatric hematologic patients receiving standard doses, with age, C-reactive protein, and alanine aminotransferase levels affecting the concentration of voriconazole in the sera of pediatric patients.

Is there still a place for serum galactomannan in the diagnosis of invasive aspergillosis in children at high risk and under antifungal prophylaxis?

The performance of serum galactomannan (GM) for the diagnosis of invasive aspergillosis (IA) has been studied mainly in adults. Paediatric data are scarce and based on small and heterogeneous cohorts. To evaluate the performance of serum GM for the diagnosis of IA in a paediatric oncologic population at high risk of IA and to clarify the impact of antifungal prophylaxis on this test. We performed a retrospective study from January 2014 to December 2020 in the paediatric oncologic haematologic department of the University Hospital of Bordeaux. The diagnosis of IA was made using the recommendations of the EORTC and the MSGERC. Among the 329 periods at high risk of IA in 222 patients, the prevalence of IA was 1.8% (3 proven and 3 probable IA). In the total population, the sensitivity, and the positive predictive value (PPV) were respectively 50% and 17.6%. Under antifungal prophylaxis, the sensitivity and PPV dropped, respectively, to 33.3% and 14.3%. In this group, the post-test probability of IA was 2% for a negative serum GM and only 14%. In this large cohort of children at high risk of IA, the incidence of IA is low and the diagnostic performance of GM is poor, especially in the case of mould-active prophylaxis. Screening should be targeted rather than systematic and should be reserved for patients at highest risk for IA without mould-active prophylaxis. Combination with other tests such as Aspergillus PCR would increase the accuracy of GM in screening setting.

Mapping the Burden of Fungal Diseases in the United Arab Emirates.

The United Arab Emirates has very little data on the incidence or prevalence of fungal diseases. Using total and underlying disease risk populations and likely affected proportions, we have modelled the burden of fungal disease for the first time. The most prevalent serious fungal conditions are recurrent vulvovaginitis (~190,000 affected) and fungal asthma (~34,000 affected). Given the UAE's low prevalence of HIV, we estimate an at-risk population of 204 with respect to serious fungal infections with cryptococcal meningitis estimated at 2 cases annually, 15 cases of Pneumocystis pneumonia (PCP) annually, and 20 cases of esophageal candidiasis in the HIV population. PCP incidence in non-HIV patients is estimated at 150 cases annually. Likewise, with the same low prevalence of tuberculosis in the country, we estimate a total chronic pulmonary aspergillosis prevalence of 1002 cases. The estimated annual incidence of invasive aspergillosis is 505 patients, based on local data on rates of malignancy, solid organ transplantation, and chronic obstructive pulmonary disease (5.9 per 100,000). Based on the 2022 annual report of the UAE's national surveillance database, candidaemia annual incidence is 1090 (11.8/100,000), of which 49.2% occurs in intensive care. Fungal diseases affect ~228,695 (2.46%) of the population in the UAE.

Investigations of an increased incidence of non-Aspergillus invasive mould infections in an onco-haematology unit.

Invasive mould infections are life-threatening complications in patients with haematologic cancer and chemotherapy-induced neutropenia. While invasive aspergillosis represents the main cause of invasive mould infections, non-Aspergillusmould infections, such as mucormycosis, are increasingly reported. Consequently, their local epidemiology should be closely monitored. The aim of this study was to investigate the causes of an increased incidence of non-Aspergillusmould infections in the onco-haematology unit of a Swiss tertiary care hospital. All cases of proven and probable invasive mould infections were retrospectively identified via a local registry for the period 2007-2021 and their incidence was calculated per 10,000 patient-days per year. The relative proportion of invasive aspergillosis and non-Aspergillusmould infections was assessed. Factors that may affect invasive mould infections' incidence, such as antifungal drug consumption, environmental contamination and changes in diagnostic approaches, were investigated. A significant increase of the incidence of non-Aspergillusmould infections (mainly mucormycosis) was observed from 2017 onwards (Mann and Kendall test p = 0.0053), peaking in 2020 (8.62 episodes per 10,000 patient-days). The incidence of invasive aspergillosis remained stable across the period of observation. The proportion of non-Aspergillusmould infections increased significantly from 2017 (33% vs 16.8% for the periods 2017-2021 and 2007-2016, respectively, p = 0.02). Building projects on the hospital site were identified as possible contributors of this increase in non-Aspergillusmould infections. However, novel diagnostic procedures may have improved their detection. We report a significant increase in non-Aspergillusmould infections, and mainly in mucormycosis infections, since 2017. There seems to be a multifactorial origin to this increase. Epidemiological trends of invasive mould infections should be carefully monitored in onco-haematology units in order to implement potential corrective measures.

Clinical Characteristics of Patients with Hematologic Malignancies and Invasive Aspergillosis: A Cross-sectional Clinical Report from Iran

Background: The incidence of invasive aspergillosis (IA) has significantly increased in recent decades. In patients with hematologic malignancies (HM), IA is associated with higher mortality rates. Objectives: This study aimed to assess the clinical features of IA in patients with HM. Methods: In this retrospective study, we used the hospital information system (HIS) database to extract clinical and paraclinical characteristics of patients with various HMs who received a diagnosis of probable or proven IA during their hospitalization at Imam Khomeini Hospital Complex in Tehran, Iran, between March 2018 and March 2022. Results: After evaluating 350 patients with HM, 51 patients with IA (14.6%) were identified, of whom 40 cases (78.4%) were probable and 11 (21.6%) were proven. Among these, 34 individuals (66.7%) were male. The most common symptoms were fever (n = 23, 62.7%), cough (n = 20, 39.2%), and fever that did not respond to antibiotic therapy (n = 16, 31.4%). The most prevalent malignancies were AML (n = 28, 54.9%), ALL (n = 16, 31.4%), and lymphoma (n = 7, 13.7%). Out of the 51 patients with HM and IA, 48 (94.1%) had abnormal findings on chest CT scans, with the majority (n = 31, 72.1%) showing a nodule with a halo sign. Aspergillus flavus (n = 19/24, 79.2%) was the most commonly isolated species. Initially, patients received liposomal amphotericin B or caspofungin as empiric antifungal therapy, which was then switched to voriconazole once the diagnosis of IA was probable or proven. Eight patients (15.6%) died. Conclusions: Patients with HM presenting with fever and cough should undergo close monitoring for IA. A higher incidence of IA is observed in AML patients, and voriconazole could be considered as antifungal prophylaxis in HM patients. A. flavus is likely the most frequent cause of IA in Iranian patients with HM.

Risk Factors and Environmental Preventive Actions for Aspergillosis in Patients with Hematological Malignancies.

(1) Background: Aspergillus spp. is a widely distributed filamentous fungus in the environment due to its high sporulation capacity. Currently, invasive aspergillosis (IA) is the most common invasive fungal infection in patients with hematologic malignancies, with high rates of mortality and morbidity. The multifactorial nature of the disease requires appropriate risk stratification to enable the most appropriate preventive measures to be adapted and implemented according to the characteristics of the patient. In this sense, the present research aims to identify recent risk factors and environmental control measures against invasive aspergillosis to establish preventive actions to reduce the incidence of invasive aspergillosis in hospitals. (2) Methods: We conducted a qualitative systematic review of the scientific literature on environmental risk factors and preventive measures for invasive aspergillosis in patients with hematologic malignancies. The Medline, Cochrane, and Scopus databases were consulted, following the PRISMA and STROBE guidelines. (3) Results: Adequate implementation of environmental control measures is presented as the most efficient intervention in terms of prevention to decrease the incidence of invasive aspergillosis in hospitals. Neutropenia, fungal contamination, insufficient environmental control measures in hospital and home settings, length of hospital stay, and anemia, are identified as independent risk factors. We show that HEPA, LAF, and Plasmair® systems are suitable methods to reduce the concentration of airborne fungal spores. Antifungal prophylaxis did not significantly influence IA reduction in our study. (4) Conclusions: Proper professional training and environmental control measures in hospitals are essential for the prevention of invasive aspergillosis. We should optimize risk stratification for patients with hematologic malignancies. Antifungal prophylaxis should be complementary to environmental control measures and should never be substituted for the latter. Studies should also be undertaken to evaluate the efficiency of environmental control measures against IA at patients' homes.

The C2H2-Type Transcription Factor ZfpA, Coordinately with CrzA, Affects Azole Susceptibility by Regulating the Multidrug Transporter Gene atrF in Aspergillus fumigatus.

The incidence of invasive aspergillosis caused by Aspergillus fumigatus has risen steadily over the past few decades due to the limited effective treatment options and the emergence of antifungal-resistant isolates. In clinic-isolated A. fumigatus, the azole resistance mechanism is primarily caused by mutations of the drug target and/or overexpression of drug efflux pumps. However, knowledge about how drug efflux pumps are transcriptionally regulated is limited. In this study, we found that loss of a C2H2 transcription factor ZfpA (zinc finger protein) results in the marked upregulation of a series of drug efflux pump-encoding genes, especially atrF, which contributes to azole drug resistance in A. fumigatus. CrzA is a previously identified positive transcription factor for genes of drug efflux pumps, and ZfpA transcriptionally inhibits expressions of drug efflux pumps in a CrzA-dependent way. Under the treatment of azoles, both ZfpA and CrzA transfer to nuclei and coregulate the expression of multidrug transporters and then keep normal drug susceptibility in fungal cells. Findings in this study demonstrated that ZfpA is not only involved in fungal growth and virulence potential but also negatively regulates antifungal drug susceptibility. IMPORTANCE Conserved across all kingdoms of life, ABC transporters comprise one of the largest protein families. They are associated with multidrug resistance, affecting aspects such as resistance to antimicrobials or anticancer drugs. Despite the importance of ABC transporters in multidrug resistance, the understanding of their regulatory network is still limited in A. fumigatus. Here, we found that the loss of the transcription factor ZfpA induces the expression of the ABC transporter gene atrF, altering azole susceptibility in A. fumigatus. ZfpA, coordinately with CrzA, affects the azole susceptibility by regulating the expression of the ABC transporter gene atrF. These findings reveal the regulatory mechanism of the ABC transporter gene atrF in A. fumigatus.

Invasive aspergillosis in liver transplant recipients.

Liver transplantation is increasing worldwide with underlying pathologies dominated by metabolic and alcoholic diseases in developed countries. We provide a narrative review of invasive aspergillosis (IA) in liver transplant (LT) recipients. We searched PubMed and Google Scholar for references without language and time restrictions. The incidence of IA in LT recipients is low (1.8%), while mortality is high (∼50%). It occurs mainly early (<3 months) after LT. Some risk factors have been identified before (corticosteroid, renal, and liver failure), during (massive transfusion and duration of surgical procedure), and after transplantation (intensive care unit stay, re-transplantation, re-operation). Diagnosis can be difficult and therefore requires full radiological and clinicobiological collaboration. Accurate identification of Aspergillus species is recommended due to the cryptic species, and susceptibility testing is crucial given the increasing resistance of Aspergillus fumigatus to azoles. It is recommended to reduce the dose of tacrolimus (50%) and to closely monitor the trough level when introducing voriconazole, isavuconazole, and posaconazole. Surgery should be discussed on a case-by-case basis. Antifungal prophylaxis is recommended in high-risk patients. Environmental preventative measures should be implemented to prevent outbreaks of nosocomial aspergillosis in LT recipient units. IA remains a very serious disease in LT patients and should be promptly sought and, if possible, prevented by clinicians when risk factors are identified.

Neutropenia-related aspergillosis in non-transplant haematological patients hospitalised under ambient air versus purified air conditions.

To reduce the risk of invasive aspergillosis (IA), air purification by high-efficiency particulate air filtration and laminar air flow (HEPA/LAF) is standard of care in allogeneic blood stem cell transplantation. Its use in non-transplant haematological patients is inconsistent. We sought to assess the incidence and outcome of pulmonary IA in non-transplant patients with life-threatening neutropenia by comparing an ambient air hospitalisation period (2008-2011) with a subsequent HEPA/LAF hospitalisation period (2012-2014). We compared 204 consecutive patients with acute myeloid leukaemia, acute lymphoblastic leukaemia or aplastic anaemia completing 534 neutropenia-related hospitalisations under ambient air conditions with 126 such patients completing 437 neutropenia-related hospitalisations under HEPA/LAF conditions. IA was defined using the 2008 EORTC/MSG criteria. Within a 7-year study period, we observed one 'proven', three 'probable' and 73 'possible' IAs, most often during acute leukaemia remission induction. Their frequency rose with increasing duration of life-threatening neutropenia (1-10 days, 1.8%; >40 days, 35.2%) and concomitant severe anaemia (0 days, 3.2%; >20 days, 31.0%). Multiple logistic regression revealed a strong correlation between IA incidence and hospitalisation under HEPA/LAF conditions (odds ratio [OR], 0.368 [95% confidence interval, 0.207-0.654]; p< .001) and duration of neutropenia (OR, 1.043 [1.023-1.062] per day; p< .001) and anaemia (OR, 1.044 [1.008-1.081] per day; p= .016). IA-associated fatal outcomes were non-significantly reduced under HEPA/LAF (OR, 0.077 [0.005-1.151]; p= .063). The protective effect of HEPA/LAF was not seen under posaconazole prophylaxis (OR, 0.856 [0.376-1.950]; p= .711). Implementation of HEPA/LAF was associated with a significant reduction in neutropenia-related IA in non-transplant haematological patients.

Effect of invasive aspergillosis on risk for different causes of death in older patients with acute myeloid leukaemia or high-risk myelodysplastic syndrome

PurposeStudy objectives were to estimate the cumulative incidence of death due to different causes of death (CODs) and investigate the effect of invasive aspergillosis (IA) on each separate COD in a cohort of older patients with acute myeloid leukaemia (AML) or high-risk myelodysplastic syndrome (MDS) included in the Haemato-Oncology Foundation for Adults in the Netherlands (HOVON) 43 randomized controlled trial.MethodsPre-collected data from the trial was obtained from the HOVON data center and relevant clinical information was extracted. The cumulative incidence of death due to different CODs was estimated with a competing risk model and the association between each COD and prognostic factors, including IA, were investigated with a cause-specific hazard Cox regression model.ResultsIn total 806 patients were included, mean age of 70 years and 55% were male. The cumulative incidences of death due to leukaemia or infection at 3, 6, 12 and 36 months were 0.06, 0.11, 0.23, 0.42 and 0.17, 0.19, 0.22, 0.25 respectively. Incidence of IA was 21% and diagnosis of IA up until the final chemotherapy cycle was associated with an increased risk of dying from leukaemia (cause-specific hazard ratio (CSHR): 1.75, 95% CI 1.34–2.28) and a trend was seen for infection (CSHR: 1.36, 95% CI 0.96–1.91).ConclusionLeukaemia was the most likely cause of death over time, however in the first year after diagnosis of AML or high-risk MDS infection was the most likely cause of death. Patients with IA had a relatively increased risk of dying from leukaemia or infection.

Updated estimation of the burden of fungal disease in Vietnam.

Anecdotally, the burden of fungal diseases in Vietnam is rapidly rising, but there has been no updated estimate on this issue since a previous report in 2015. In this study, we aimed at estimating the incidence and prevalence of serious fungal infections for the year 2020. We made estimates with a previously described methodology, using reports on the incidence and prevalence of various established risk factors for fungal infections from local, regional or global sources. We estimated 2,389,661 cases of serious fungal infection occurred in Vietnam in 2020. The most common condition was recurrent vaginal candidiasis (4047/100,000 women annually). Among people living with HIV, we estimated 451 cases of cryptococcal meningitis, 1030 of pneumocystis pneumonia, 166 of histoplasmosis and 1612 of talaromycosis annually. Candidaemia incidence was estimated at 12/100,000 population each year. Owing to its high burden of tuberculosis and respiratory diseases, Vietnam had high rates of severe infections caused by Aspergillus species. Incidence of invasive aspergillosis is 24/100,000 population, allergic bronchopulmonary aspergillosis 78/100,000 and severe asthma with fungal sensitisation 102/100,000. Five-year period prevalence of chronic pulmonary aspergillosis is 120/100,000 population /5-year period. Mucormycosis, fungal keratitis and tinea capitis were estimated at 192, 14,431 and 201 episodes each year, respectively. The number of patients with mycoses in Vietnam is likely underestimated due to a lack of local data and limited diagnostic capacity, but at least 2.5% of the population might have some form of serious fungal disease.

Invasive Aspergillosis and Candidiasis in a Patient with Supraglottic Carcinoma undergoing Chemoradiotherapy: A Case Report

The incidence of Invasive Aspergillosis (IA) is increasing. Early diagnosis and treatment are very important to improve patient survival, especially in immunocompromised patients. The diagnosis of IA is challenging as clinical indicators are limited, and early microbiological confirmation of the infection is infrequent. Here, the authors present the case of a 43-year-old male who was undergoing radiotherapy along with concurrent chemotherapy for carcinoma supraglottis. He developed Invasive Pulmonary Aspergillosis (IPA) along with candidiasis within two weeks of therapy. Voriconazole remains the recommended therapy for patients with IA, which also acts against fluconazole-resistant Candida species.

Impact of COVID-19 pandemic on antifungal consumption: a multicenter retrospective analysis

BackgroundIn the context of COVID-19 pandemic, antifungal overuse may have occurred in our hospitals as it has been previously reported for antibacterials.MethodsTo investigate the impact of COVID-19 on antifungal consumption, a multicenter retrospective study including four medical sites and 14 intensive care units (ICU) was performed. Antifungal consumption and incidences of invasive fungal diseases before and during COVID-19 pandemic, for non-COVID-19 patients and COVID-19 patients, were described.ResultsAn increase in voriconazole consumption was observed in 2020 compared with 2019 for both the whole hospital and the ICU (+ 40.3% and + 63.7%, respectively), whereas the incidence of invasive aspergillosis significantly increased in slightly lower proportions in the ICU (+ 46%). Caspofungin consumption also increased in 2020 compared to 2019 for both the whole hospital and the ICU (+ 34.9% and + 17.0%, respectively) with an increased incidence of invasive candidiasis in the whole hospital and the ICU but in lower proportions (+ 20.0% and + 10.9%, respectively).ConclusionsWe observed an increased consumption of antifungals including voriconazole and caspofungin in our hospital during the COVID-19 pandemic and explained in part by an increased incidence of invasive fungal diseases in COVID-19 patients. These results are of utmost importance as it raises concern about the urgent need for appropriate antifungal stewardship activities to control antifungal consumption.

COVID-19-Associated Pulmonary Aspergillosis in a Series of Complete Autopsies from the Brazilian Amazon.

ABSTRACT.Between April and July 2020, and, therefore, prior to the broad recommendation of corticosteroids for severe COVID-19, a total of 50 full autopsies were performed in Manaus. We confirmed two invasive cases of aspergillosis through histopathology and gene sequencing (4%) in our autopsy series. The confirmed invasive aspergillosis incidence seems much lower than expected based on the “probable and possible” definitions, and an individualized approach should be considered for each country scenario. Interestingly, a prolonged length of stay in the intensive care unit was not observed in any of the cases. Timely diagnosis and treatment of fungal infection can reduce mortality rates.

A Novel Strategy to Identify Haematology Patients at High Risk of Developing Aspergillosis.

Invasive Aspergillosis (IA), typically caused by the fungus Aspergillus fumigatus, is a leading cause of morbidity and mortality in immunocompromised patients. IA remains a significant burden in haematology patients, despite improvements in the diagnosis and treatment of Aspergillus infection. Diagnosing IA is challenging, requiring multiple factors to classify patients into possible, probable and proven IA cohorts. Given the low incidence of IA, using negative results as exclusion criteria is optimal. However, frequent false positives and severe IA mortality rates in haematology patients have led to the empirical use of toxic, drug-interactive and often ineffective anti-fungal therapeutics. Improvements in IA diagnosis are needed to reduce unnecessary anti-fungal therapy. Early IA diagnosis is vital for positive patient outcomes; therefore, a pre-emptive approach is required. In this study, we examined the sequence and expression of four C-type Lectin-like receptors (Dectin-1, Dectin-2, Mincle, Mcl) from 42 haematology patients and investigated each patient’s anti-Aspergillus immune response (IL-6, TNF). Correlation analysis revealed novel IA disease risk factors which we used to develop a pre-emptive patient stratification protocol to identify haematopoietic stem cell transplant patients at high and low risk of developing IA. This stratification protocol has the potential to enhance the identification of high-risk patients whilst reducing unnecessary treatment, minimizing the development of anti-fungal resistance, and prioritising primary disease treatment for low-risk patients.

Invasive aspergillosis in relapsed/refractory acute myeloid leukaemia patients: Results from SEIFEM 2016-B survey.

In patients with relapsed/refractory acute myeloid leukaemia (R/R AML) who received salvage chemotherapy, limited and not updated studies explored the incidence of invasive aspergillosis (IA) and the role of antifungal prophylaxis (AP). The aims of this multicentre retrospective 'SEIFEM 2016-B' study were as follows: (1) to evaluate the current rate and the outcome of proven/probable IA and (2) to assess the efficacy of AP, in a large 'real life' series of patient with R/R AML submitted to salvage chemotherapy. Of 2250 R/R AML patients, a total of 74 cases of IA (5.1%) were recorded as follows: 10 (0.7%) proven and 64 (4.3%) probable. Information about AP were available in 73/74 (99%) patients. Fifty-eight (79%) breakthrough infections occurred, mainly during AP with posaconazole [25 (43%)]. The patients who received AP during salvage chemotherapy showed a benefit from antifungal therapy (AT) than patients who did not received AP [43 (86%) vs 7 (14%); p<.033]. In a multivariate analysis, AP and absence of severe mucositis had a significant favourable effect on overall response rate. Our data demonstrated that the incidence of IA during the salvage chemotherapy is similar to the past. Nevertheless, the attributable mortality rate (AMR) appears to be lower than that previously reported in R/R AML. Further prospective studies should be performed to confirm our preliminary observation and understand and the why a decreased AMR is reported in this setting of high-risk patients.

Novel treatment possibilities of invasive aspergillosis

Invasive aspergillosis is the leading fungal infection in patients with hematological malignancies. The review represents the incidence of invasive aspergillosis in different groups of patients, risk factors for its development, treatment options, including the new drug isavuconazole.

Invasive Aspergillosis in Allogeneic Hematopoietic Stem Cell Transplantation Recipients: A Large Cohort Single-Center Study

Background. Invasive aspergillosis (IA) is dominant among invasive fungal infections after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The emergence of new immunosuppressive drugs, the expanding use of antifungal agents with activity against Aspergillus spp. on the one hand, and the improvement of the diagnostics and therapy on the other hand affect epidemiology of IA.Methods. We analyzed 663 patients who underwent allo-HSCT from 2016 to 2020 years in CIC 725. During the observation period, 43 patients with proven and probable IA were included into analysis. According to EORTC/MSG 2019 criteria, 2 proven and 41 probable cases were diagnosed in adults with hematological malignances and non-malignant hematological diseases during 1 year after allo-HSCT. We characterized the IA after allo-HSCT and conducted the comparative analysis of patients and transplant characteristics who developed IA after allo-HSCT and did not. The median follow up time was 13,9 months.Results. Cumulative incidence of IA during 1-year period after allo-HSCT was 8%. Among all cases of IA most common underlying diagnoses were acute leukemia - 32% and lymphomas - 30%. The main sites of infection were lungs 93%, sinuses - 2%, disseminated lesions - 5%. The IA was diagnosed by bronchoalveolar (BAL) or sinuses liquid culture in 54% cases, and the etiology were Aspergillus fumigatus - 8 (42%), Aspergillus niger - 5 (26%), Aspergillus flavus - 2 (11%), Aspergillus terreus - 1 (5%), Aspergillus spp. - 3 (16%). The median day of IA onset was day +59 (range, 2 to 282) after allo-HSCT. First line therapy of IA was predominantly with voriconazole (vori) monotherapy - 35 (81%), combination based on vori - 5 (12%). Salvage combination therapy were prescribed in two patients: vori + echinocandins (echino) and L amph B + echino. Overall survival at 12 weeks in patients with IA was 76%. Comparative analysis showed that in patients with IA statistically significant more frequent were patients with AML, HL, NHL, Ph(-) MPNs, second or more allo-HSCT, CMV-reactivation, aGVHD, aGVHD grade 3-4, severe chGVHD (Table 1). To identify the risk factors including primary antifungal prophylaxis planning to conduct the multivariate subgroup analysis. Patients with IA had lower level of lymphocytes on day +60 (p=0.006) and 100 (p=0.009) compared to patients without IA (pic.1).Conclusions. Incidence of IA after allo-HSCT was 8% with the median day +59. The main site of infection was lungs, etiology - Aspergillus fumigatus. Overall survival at 12 weeks in patients with IA was 76%. In the era of primary and secondary prophylaxis we identified risk groups for developing IA after allo-HSCT among the previously undescribed, worthy of further study: subsequent allo-HSCT, underlying disease: HL, NHL, Ph (-) MPNs. [Display omitted] DisclosuresKlimko: Gilead Sciences, MSD, Pfizer Pharmaceuticals, and Astellas Pharma: Speakers Bureau; Gilead Science, MSD, Pfizer: Membership on an entity's Board of Directors or advisory committees. Kulagin: Pfizer: Speakers Bureau; Johnson & Johnson: Speakers Bureau; Roche: Speakers Bureau; Sanofi: Speakers Bureau; Generium: Speakers Bureau; Biocad: Research Funding; Apellis: Research Funding; Alexion: Research Funding; X4 Pharmaceuticals: Research Funding; Novartis: Speakers Bureau.

Weekly high-dose liposomal amphotericin B prevents invasive aspergillosis after heart transplantation.

Preventive strategies for invasive aspergillosis (IA) have still not been determined in heart transplant recipients whereas IA leads to a high mortality rate at 12 months posttransplantation. The use of voriconazole or echinocandins was proposed but can favor emergence of Aspergillus or Candida sp. resistant strains or promote neurological and liver disorders in some patients. To assess whether universal prophylaxis with weekly high-dose of liposomal amphotericin-B (L-AmB) can safely prevent IA in heart transplant recipients. Retrospective before/after study that included 142 patients who received heart transplantation between 2010 and 2019 at the University Hospital of Toulouse (France). Weekly high dose of L-AmB (7.5 mg/kg/week) was used as universal prophylaxis from 2016 because of high environmental exposure to Aspergillus sp. and high incidence of IA. Cumulative 1-year incidence of IA decreased from 23% to 5% after introduction of L-Amb prophylaxis. Multivariate analysis (Cox model) identified L-AmB prophylaxis as a protective factor against IA (hazard ratio [HR] 0.21 [95% confidence interval 0; 0.92], p = .04), whereas postoperative renal replacement therapy was associated with IA (HR 3.6 [95% confidence interval 1.38; 9.3], p = .001), after correction for confounding effects (induction regimen, methylprednisolone pulses and history of hematological malignancy). The incidence of acute kidney injury requiring renal replacement therapy was similar in the two groups, suggesting a low risk of kidney toxicity when L-AmB is used weekly. No patient developed severe kidney electrolyte loss nor L-AmB-related anaphylaxis. Once-weekly high-dose L-AmB is safe and may prevent the development of IA after heart transplantation.

Estimated burden of serious fungal infections in Togo.

Over the years, the focus of infectious diseases in many African countries has been mainly on viral, bacterial and parasitic infections. Serious fungal infections (SFIs) with comparable morbidity rate in these countries remain neglected. To estimate the burden of SFI in Togo and to stimulate efforts for improved attention. Literature was thoroughly searched for epidemiological data on SFI in Togo. Incidence and/or prevalence of SFI was estimated using socio-demographics, health system's information, risk-groups data and SFI rates obtained from national and international studies. About 5.29% of the 7,265,286 Togolese population is estimated to suffer from SFI annually. Among HIV patients, 1,342, 1,650 and 330 may develop cryptococcal meningitis, Pneumocystis pneumonia and disseminated histoplasmosis respectively per year. Oral and oesophageal candidiasis may annually affect 19,800 and 7,535 persons, respectively, living with HIV. Estimated incidence of invasive aspergillosis (IA) was 283 cases. Prevalence of chronic pulmonary aspergillosis (CPA) was estimated at 191 cases. The annual incidence of allergic bronchopulmonary aspergillosis (ABPA) and severe asthma with fungal sensitization (SAFS) was 4,577 and 6,042 cases, respectively. Tinea capitis and recurrent Candida vaginitis presumably affect 232,271 children and 108,979 women respectively. Candidaemia incidence is estimated at 5 cases per 100, 000 inhabitants and fungal keratitis may affect 981 persons annually. SFIs in Togo are probably more significant than expected. These findings underscore the need to increase awareness among healthcare professionals, enhance diagnostic and therapeutic capacities and intensify epidemiological studies for effective management of fungal infections in Togo.