Long term management of people with post-tuberculosis lung disease.

Post-tuberculosis lung disease (PTLD) is emerging as a significant area of global interest. As the number of patients surviving tuberculosis (TB) increases, the subsequent long-term repercussions have drawn increased attention due to their profound clinical and socioeconomic impacts. A primary obstacle to its comprehensive study has been its marked heterogeneity. The disease presents a spectrum of clinical manifestations which encompass tracheobronchial stenosis, bronchiectasis, granulomas with fibrosis, cavitation with associated aspergillosis, chronic pleural diseases, and small airway diseases-all persistent consequences of PTLD. The spectrum of symptoms a patient may experience varies based on the severity of the initial infection and the efficacy of the treatment received. As a result, the long-term management of PTLD necessitates a detailed and specific approach, addressing each manifestation individually-a tailored strategy. In the immediate aftermath (0-12 months after anti-TB chemotherapy), there should be an emphasis on monitoring for relapse, tracheobronchial stenosis, and smoking cessation. Subsequent management should focus on addressing hemoptysis, managing infection including aspergillosis, and TB-associated chronic obstructive pulmonary disease or restrictive lung function. There remains a vast expanse of knowledge to be discovered in PTLD. This review emphasizes the pressing need for comprehensive, consolidated guidelines for management of patients with PTLD.

Incidence of invasive fungal diseases in inflammatory bowel disease patients: A nationwide study in South Korea.

BACKGROUND: Limited reports exist regarding invasive fungal diseases (IFDs) in inflammatory bowel disease (IBD) patients. OBJECTIVES: This study aims to investigate the incidence and risk factors of IFDs, specifically invasive candidiasis, aspergillosis and pneumocystosis, in IBD patients in South Korea using nationwide data. PATIENTS/METHODS: A population-based retrospective cohort of 42,913 IBD patients between January 2010 and December 2018 was evaluated using the Health Insurance Review and Assessment database. The primary outcome was the incidence of IFDs, including invasive candidiasis, aspergillosis and pneumocystosis, while the secondary outcome involved analysing the risk factors associated with each specific infection. RESULTS: The study included a total of 42,913 IBD patients, with 29,909 (69.7%) diagnosed with ulcerative colitis (UC) and 13,004 (30.3%) diagnosed with Crohn's disease (CD). IFDs occurred in 166 IBD patients (0.4%), with 93 cases in UC patients and 73 cases in CD patients. The incidence rates of invasive candidiasis, aspergillosis and pneumocystosis in IBD patients were 0.71 per 1000 person-years (PYs), 0.15 per 1000 PYs and 0.12 per 1000 PYs, respectively. The cumulative incidence of invasive candidiasis (adjusted p-value <.001) and Pneumocystosis (adjusted p-value = .012) was found to be higher in CD patients than in UC patients. Each IFD had different risk factors, including IBD subtypes, age at diagnosis, anti-tumour necrotic factor agents or the Charlson comorbidity index. CONCLUSION: Based on nationwide data in South Korea, this study shows that IFDs occur consistently in patients with IBD, albeit with a low frequency.

Invasive fungal infection in ANCA-associated vasculitis: Between the Devil and Deep blue sea. Case series and review of the literature.

INTRODUCTION: Patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV) are susceptible to opportunistic infections, including invasive fungal infections (IFI). This is due to many factors, including prolonged immunosuppressive therapy. The treatment of AAV with such IFIs is challenging. METHODS: A descriptive analysis of 5 patients with AAV complicated by concomitant invasive fungal infections was performed. We also have done a comprehensive literature review of IFIs in AAV using PubMed and Google Scholar databases. RESULTS: All 5 patients initially received immunosuppressive medication but subsequently acquired IFI. One patient had sphenoid sinus involvement, and four had lung parenchymal involvement. Aspergillus infection was diagnosed in three patients, Cryptococcus infection in one patient and mixed infection with Aspergillus and Mucor infection in one patient. All our patients were on low doses of corticosteroids for several months to years or had received high-dose pulse steroids with cyclophosphamide in the last few weeks before being diagnosed with IFI. It was difficult to distinguish disease activity from IFI in all the cases. Two of the five patients died despite antifungal therapy. The literature review revealed a prevalence of IFIs ranging from 1 to 9.6% (excluding pneumocystis pneumonia). Aspergillosis was the predominant type of IFI, affecting 46 of 86 patients. Most of these patients (40/46) had pulmonary involvement. The prognosis for patients with IFI was consistently poor, as evidenced by 19 deaths out of 29 reported outcomes. CONCLUSION: Overall, IFIs have a poor prognosis in patients with AAV. Differentiating disease activity from IFI is difficult because of similar organ distribution, imaging lesions, and histopathological characteristics. A high suspicion index and good-quality microbiology are needed for early treatment and prevention of mortality.

Fatal pulmonary hemorrhage, pneumothorax and skin necrosis caused by IRIS to an Aspergillus flavus infection in a young patient with metamizole associated agranulocytosis.

We report the case of a young female with steroid-dependent ulcerative colitis (UC) who developed a complex systemic infection with Aspergillus flavus. This occurred following a UC relapse while vacationing in the Middle East, leading to extended use of metamizole and subsequent agranulocytosis. On her return to Germany, she was hospitalized for neutropenic sepsis and later transferred to our hospital due to persistent cytopenia and suspected Hemophagocytic Lymphohistiocytosis (HLH). Despite initial stabilization with targeted treatment for pulmonary Aspergillus flavus infection, her condition rapidly deteriorated following the onset of an Immune Reconstitution Inflammatory Syndrome (IRIS), which manifested as skin necrosis and pneumothorax after the replenishment of neutrophil granulocytes. The patient eventually died from an unmanageable pulmonary hemorrhage. Microscopy of skin necroses showed a massive presence of Aspergillus flavus, but tissue culture remained negative, suggesting effective antifungal treatment yet delayed phagocytosis due to agranulocytosis. This case underscores the need to consider IRIS in immunosuppressed patients who worsen despite aggressive and appropriately targeted treatment, highlighting its potential beyond the commonly recognized context in HIV-positive patients.

Endocarditis caused by Aspergillus fumigatus in a patient 9 months after COVID-19 infection recovery: a case report and review of the literature.

BACKGROUND: Aspergillus spp. are among the fungal pathogens that can cause life-threatening infections in patients with a history of COVID-19. CASE PRESENTATION: We present the case of a 58-year-old Iranian woman with post-COVID-19 Aspergillus fumigatus endocarditis complicated by numerous thromboembolisms. She underwent mitral valve replacement surgery and multiple lower extremity embolectomies and was treated with voriconazole, which led to her final recovery. CONCLUSIONS: Aspergillus endocarditis should be considered in any patient with suspected endocarditis who has a history of COVID-19 infection and does not respond to routine antibiotic and antifungal therapy, as COVID-19 interferes with proper immune function, and lack of underlying cardiac conditions and immunodeficiencies does not preclude the diagnosis. Culture and histopathological evaluation of vegetations and emboli, as well as PCR, can confirm the diagnosis. Early initiation of antifungal therapy and surgical removal of infected valves and emboli can improve prognosis in patients with Aspergillus endocarditis.

Evolution of neuroimaging findings in angioinvasive cerebral aspergillosis in a pediatric patient with leukemia during long-term observation.

The central nervous system is one of the most common sites of aspergillosis involvement in immunocompromised people, just after sinopulmonary infections. Neuroimaging modalities are crucial for the diagnosis of cerebral aspergillosis (CA). Here, we describe a rare case of concurrent mixed aspergillosis infection with Aspergillus fumigatus and Aspergillus niger in a 2-year-old leukemic boy. The first neuroimaging finding, which was followed by focal seizures, was recognized as extensive cerebral hemorrhage in the absence of thrombocytopenia and coagulopathy. As the patient survived for more than 4 months after diagnosis, we were able to perform a neuroimaging evaluation during long-term observation. In serial neuroimaging studies, a secondary fungal abscess was observed at the site of hemorrhagic infarctions. Finally, the patient died from bacterial sepsis. In this case study, we try to categorize the neuroimaging findings of CA into distinct phases to better understand how CA changes over time.

Systemic aspergillosis associated with acute enterocolitis in foals.

Aspergillosis is an uncommon disease in horses, but it can be fatal. We report two cases of systemic aspergillosis in foals that occurred in a short period in the same region of southern Brazil. In addition, a literature review of similar cases was also performed. Risk factors were attributed to an immunodepression by primary enterocolitis and corticosteroid treatment, the damage in the epithelium, and multiple antibacterial treatments, which allowed local fungal proliferation, tissue invasion and spread of infection, leading to death. Since the antemortem diagnosis of aspergillosis in foals is difficult, our report alerts equine veterinarians regarding the importance of suspecting and investigating fungal co-infections in complicated cases of enterocolitis.

[An unusual brain lesion]. / Un lésion cérébrale déroutante.

A 31-year-old man, with no past medical history, presented with headaches, sudden loss of vision, right exophtalmia, bilateral papilledema, and fever. Brain imaging noted a right basi-temporal lesion. Excision of the lesion was performed. The histological examination noted a glial tissue with acute inflammatory changes and multinucleated giant cells. Within this infiltrate there were septate and branched hyphae consistent with aspergillosis. These filaments were stained with PAS. The patient died post-operatively.

Endogenous Aspergillus thermomutatus Endophthalmitis in a Patient With Myelodysplastic Syndrome.

This case report describes a diagnosis of Aspergillus thermomutatus endophthalmitis in a patient with a recent history of allogeneic stem cell transplant.

Systemic lupus erythematosus associated with development of macrophage activation syndrome and disseminated aspergillosis.

PURPOSE: Macrophage activation syndrome (MAS) is a rare illness, especially in critically ill adults. The diagnosis of MAS is challenging, requiring the expertise of multiple specialists, and treatments for MAS can be associated with catastrophic complications. CLINICAL FEATURES: We describe the case of a 31-yr-old Vietnamese student who was diagnosed with cutaneous systemic lupus erythematosus (SLE) in November 2020 and was initiated on treatment with low-dose corticosteroids and hydroxychloroquine as an outpatient. Ten days later, she presented to hospital with decreased consciousness, fever, periorbital swelling, and hypotension necessitating intubation. Computed tomography angiography (CTA) and lumbar puncture did not show a stroke or central nervous system infection. Serology and clinical presentation were consistent with MAS. She was initially treated with 4.5 g pulse methylprednisolone and subsequently with the interleukin-1 receptor antagonist, anakinra, and maintenance corticosteroids because of persistently elevated inflammatory markers. Her intensive care unit stay was complicated by aspiration, airway obstruction due to fungal tracheobronchitis necessitating extracorporeal membrane oxygenation (ECMO), and ring-enhancing cerebral lesions, and, ultimately, massive hemoptysis resulting in death. CONCLUSIONS: Four features of this case merit discussion, including the: 1) infrequent association of SLE with MAS; 2) short interval between SLE diagnosis and critical illness; 3) manifestation of fungal tracheobronchitis with airway obstruction; and 4) lack of response to antifungal treatment while receiving ECMO.

RéSUMé: OBJECTIF: Le syndrome d'activation macrophagique (SAM) est une maladie rare, en particulier chez les adultes gravement malades. Le diagnostic d'un SAM est difficile à poser, nécessitant l'expertise de plusieurs spécialistes, et les traitements de ce syndrome peuvent être associés à des complications catastrophiques. CARACTéRISTIQUES CLINIQUES: Nous décrivons le cas d'une étudiante vietnamienne de 31 ans ayant reçu un diagnostic de lupus érythémateux disséminé (LED) cutané en novembre 2020; un traitement par corticostéroïdes à faible dose et hydroxychloroquine a été amorcé en ambulatoire. Dix jours plus tard, elle s'est présentée à l'hôpital avec une diminution de la conscience, de la fièvre, un gonflement périorbitaire et une hypotension nécessitant une intubation. L'angiographie par tomodensitométrie et la ponction lombaire n'ont pas révélé d'accident vasculaire cérébral ou d'infection du système nerveux central. La sérologie et la présentation clinique correspondaient à celles d'un SAM. Elle a d'abord été traitée avec 4,5 g de méthylprednisolone en injection ponctuelle, puis avec un antagoniste du récepteur à l'interleukine-1, l'anakinra et des corticostéroïdes d'entretien en raison de marqueurs inflammatoires élevés persistants. Son séjour en soins intensifs a été compliqué par une aspiration, une obstruction des voies aériennes due à une trachéobronchite fongique nécessitant une oxygénation par membrane extracorporelle (ECMO) et des lésions cérébrales avec rehaussement en anneau, et finalement une hémoptysie massive entraînant la mort. CONCLUSION: Quatre caractéristiques de ce cas méritent d'être discutées, soit: 1) l'association peu fréquente du lupus érythémateux disséminé avec un syndrome d'activation macrophagique; 2) le court intervalle entre le diagnostic de LED et la maladie grave; 3) l'apparition d'une trachéobronchite fongique avec obstruction des voies aériennes; et 4) l'absence de réponse au traitement antifongique pendant le traitement par ECMO.

Appropriate Total Rehabilitation in the Bilateral Maxillectomy Defected Diabetic Patient Secondary to Aggressive Aspergillosis.

Aggressive aspergillosis is a life-threatening fungal infection with rapid progress, mainly affecting the maxillofacial area, especially the nose and paranasal sinuses, in patients with immunocompromised conditions such as diabetes mellitus. Aggressive aspergillosis infection should be differentiated from other invasive fungal sinusitis for early recognition with correct prompt treatment. The main treatment is aggressive surgical debridement such as maxillectomy. Although aggressive debridement should be performed, preservation of the palatal flap should be considered for better postoperative outcomes. In this manuscript, we report the case of a diabetic patient with aggressive aspergillosis affecting the maxilla and paranasal sinuses and describe the appropriate surgical management and prosthodontic rehabilitation.

Role of COPD in a case of fatal Aspergillus niger tracheobronchitis.

A man with chronic obstructive pulmonary disease (COPD) in his mid-60s was admitted for respiratory failure due to multifocal, necrotising pneumonia. Despite initial improvement with antimicrobial therapy, the patient developed hemoptysis and progressive infiltrates. Subsequent fungal cultures from his bronchoalveolar lavage were positive for Aspergillus niger and treatment with voriconazole was added for suspected invasive pulmonary aspergillosis (IPA). A repeat bronchoscopy revealed cobblestone lesions with mucosal friability throughout the lower trachea and bilateral mainstem bronchi. Endobronchial biopsy showed septated hyphae confirming the diagnosis of IPA. Despite appropriate therapy, the patient declined further and passed away on hospital day 11. Invasive infections with A. niger are infrequent, with a paucity of data on clinical course and outcomes. Our case adds to the current body of literature regarding the potential virulence of this species in patients with COPD.

[Intralobar Sequestration Associated with Aneurysm of the Aberrant Artery and Aspergillus Infection: Report of a Case].

A 32-year-old man was referred to our department for surgery because of recurrent pneumonia. Aspergillus fumigatus was detected in his sputum culture at the first visit. We started antifungal therapy one month before surgery. His chest radiograph showed an infiltrative shadow in the right lower lobe, and chest computed tomography (CT) showed an infiltrative shadow and large and small cystic changes in the right lower lobe. CT angiography (CTA) revealed two anomalous arteries supplied by the aorta that drained into the right lower lobe. An aneurysm with a diameter of 25 mm had formed in one anomalous artery. Based on these findings, intralobar pulmonary sequestration with Aspergillus infection and an anomalous artery forming an aneurysm was diagnosed. In addition, we embolized the aneurysm of the anomalous artery. After embolization, right lower lobectomy was safely performed. The patient was discharged on the 15th post-operative day with no complications.

Clinical characteristics, diagnosis, outcomes and lung microbiome analysis of invasive pulmonary aspergillosis in the community-acquired pneumonia patients.

BACKGROUND: Invasive pulmonary aspergillosis (IPA) remains underestimated in patients with community-acquired pneumonia (CAP). This study aims to describe clinical features and outcomes of IPA in CAP patients, assess diagnostic performance of metagenomic next-generation sequencing (mNGS) for IPA and analyse lung microbiome via mNGS data. METHODS: This retrospective cohort study included CAP patients from 22 April 2019 to 30 September 2021. Clinical and microbiological data were analysed. Diagnostic performance of mNGS was compared with traditional detection methods. The lung microbiome detected by mNGS was characterised and its association with clinical features was evaluated. MAIN RESULTS: IPA was diagnosed in 26 (23.4%) of 111 CAP patients. Patients with IPA displayed depressed immunity, higher hospital mortality (30.8% vs 11.8%) and intensive care unit mortality (42.1% vs 17.5%) compared with patients without IPA. The galactomannan (GM) antigen test had the highest sensitivity (57.7%) in detecting the Aspergillus spp, followed by mNGS (42.3%), culture (30.8%) and smear (7.7%). The mNGS, culture and smear had 100% specificity, while GM test had 92.9% specificity. The microbial structure of IPA significantly differed from non-IPA patients (p<0.001; Wilcoxon test). Nineteen different species were significantly correlated with clinical outcomes and laboratory biomarkers, particularly for Streptococcus salivarius, Prevotella timonensis and Human betaherpesvirus 5. CONCLUSIONS: Our results reveal that patients with Aspergillus infection tend to have a higher early mortality rate. The mNGS may be suggested as a complement to routine microbiological test in diagnosis of patients at risk of Aspergillus infection. The lung microbiota is associated with inflammatory, immune and metabolic conditions of IPA, and thus influences clinical outcomes.