Pulmonary dimorphic fungal infections among HIV/AIDS non-TB patients with chronic cough in Kampala, Uganda.

INTRODUCTION: Dimorphic fungi cause infection following the inhalation of spores into the pulmonary system. In the lower respiratory tract, the conidia transform into yeasts, which are engulfed by alveolar macrophages and may be destroyed without disease manifestation. However, in some immunocompromised individuals, they may persist and cause active fungal disease characterized by formation of granulomas in the infected tissues, which may mimic Mycobacterium tuberculosis (MTB). OBJECTIVE: To determine the prevalence of pulmonary dimorphic fungal infections among HIV/AIDS patients with non-TB chronic cough at Mulago National Referral and Teaching Hospital in Kampala, Uganda. METHODS: Sputum samples were collected from 175 consented HIV/AIDS patients attending the immuno-suppression syndrome (ISS) clinic at the hospital. Upon Xpert MTB/RIF sputum testing, 21 patients tested positive for MTB, and these were excluded from further analysis. The other 154 sputum negative samples were then subjected to PCR for dimorphic fungi at MBN Clinical Laboratories. Singleplex PCR was used to detect the target sequences in selected respective genes of each dimorphic fungal species of interest. DNA amplicons were detected based on gel electrophoresis. RESULTS: Dimorphic fungi were detected in 16.2% (25/154) of the studied population. Of these 9.1% (14/154) had Blastomyces dermatitidis and 7.1% (11/154) had Talaromyces marneffei. The remaining 84% of the studied participants had no dimorphic fungi. Histoplasma capsulatum, Coccidioides immitis and Paracoccidioides brasiliensis were not detected in any of the participants. CONCLUSION: Dimorphic fungi (B. dermatitidis and T. marneffei) were found in 16.2% of the HIV/AIDS patients with non-TB chronic cough in Kampala, Uganda. We recommend routine testing for these pathogens among HIV/AIDS patients with chronic cough.

Hormographiella aspergillata pulmonary infections: Detection and identification of the fungus using pan-fungal PCR assays and DNA sequencing.

Hormographiella aspergillata is a basidiomycete exceptionally involved in invasive fungal infections (IFI). We report a case of H. aspergillata pulmonary infection in a 30-year-old female in a context of pancytopenia and relapsed of acute myeloid leukemia (AML). She presented with fever, thoracic pain, left pleural effusion and pneumonia, diagnosed on chest X-ray and CT-scan. Direct examination of a bronchoalveolar lavage (BAL) specimen performed on day (d) 10 was negative, while the culture was positive on d30. H. aspergillata was suspected, considering macroscopic and microscopic examination. Its identification was confirmed using Microflex® Bruker mass spectrometry and pan-fungal (PF)-PCR assay followed by DNA sequencing. After this initial diagnosis, the patient was monitored for 2.8 years. She was treated with liposomal amphotericin B and/or voriconazole until switching to isavuconazole on d298 due to side-effects. This antifungal treatment was maintained until d717 and then discontinued, the patient being considered as cured. Over this follow-up period, the patient was submitted to recurrent pulmonary sampling. Each time, cultures were negative, while PF - PCR assays and DNA sequencing confirmed the presence of H. aspergillata. The present case-report is the 32nd observation of H. aspergillata invasive infection showing that this IFI is still infrequent. Fifteen have occurred in patients with AML, which appears as the most frequent underlying disease favoring this IFI. Six recent case-reports in addition to ours highlight PF-PCR assays and DNA sequencing as relevant diagnostic tools that must be included in routine diagnosis and monitoring of IFI, specifically those due to rare basidiomycetes.

Improving Diagnosis of Pulmonary Mucormycosis: Leads From a Contemporary National Study of 114 Cases.

BACKGROUND: Pulmonary mucormycosis (PM) is a life-threatening invasive mold infection. Diagnosis of mucormycosis is challenging and often delayed, resulting in higher mortality. RESEARCH QUESTION: Are the disease presentation of PM and contribution of diagnosis tools influenced by the patient's underlying condition? STUDY DESIGN AND METHODS: All PM cases from six French teaching hospitals between 2008 and 2019 were retrospectively reviewed. Cases were defined according to updated European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria with the addition of diabetes and trauma as host factors and positive serum or tissue PCR as mycologic evidence. Thoracic CT scans were reviewed centrally. RESULTS: A total of 114 cases of PM were recorded, including 40% with disseminated forms. Main underlying conditions were hematologic malignancy (49%), allogeneic hematopoietic stem cell transplantation (21%), and solid organ transplantation (17%). When disseminated, main dissemination sites were the liver (48%), spleen (48%), brain (44%), and kidneys (37%). Radiologic presentation included consolidation (58%), pleural effusion (52%), reversed halo sign (26%), halo sign (24%), vascular abnormalities (26%), and cavity (23%). Serum quantitative polymerase chain reaction (qPCR) was positive in 42 (79%) of 53 patients and BAL in 46 (50%) of 96 patients. Results of transthoracic lung biopsy were diagnostic in 8 (73%) of 11 patients with noncontributive BAL. Overall 90-day mortality was 59%. Patients with neutropenia more frequently displayed an angioinvasive presentation, including reversed halo sign and disseminated disease (P < .05). Serum qPCR was more contributive in patients with neutropenia (91% vs 62%; P = .02), and BAL was more contributive in patients without neutropenia (69% vs 41%; P = .02). Serum qPCR was more frequently positive in patients with a > 3 cm main lesion (91% vs 62%; P = .02). Overall, positive qPCR was associated with an early diagnosis (P = .03) and treatment onset (P = .01). INTERPRETATION: Neutropenia and radiologic findings influence disease presentation and contribution of diagnostic tools during PM. Serum qPCR is more contributive in patients with neutropenia and BAL examination in patients without neutropenia. Results of lung biopsies are highly contributive in cases of noncontributive BAL.

Pulmonary infection of Schizophyllum commune diagnosed by metagenomic next- generation sequencing: A case report.

RATIONALE: Fungal infection is common and difficult to be diagnosed timely in clinical, for its various kinds and similar manifestations. The rare pulmonary fungal infection such as Schizophyllum commune was one of the harder ones and misdiagnosed in usual. PATIENT CONCERNS: We report a 32-year-old female which was diagnosed with Metagenomic Next-Generation Sequencing (mNGS). She was hospitalized with the complaint of 4 months and more of repeated cough and expectorating. The chest computer tomography revealed left lower lobe pathological changes, but antibiotics were ineffective. No positive results were found in laboratory tests, including sputum culture and the pathology of lung puncture biopsy. DIAGNOSES: mNGS of lung biopsy was performed and detected the sequence number of Schizophyllum for 11. INTERVENTIONS: The patient was treated with voriconazole and itraconazole successively. OUTCOMES: She recovered to health. There was no recurrence during follow-up. LESSONS: mNGS as a diagnostic method could quickly detect pathogens through the processing of fragment, synthesis, comparison, and analysis of sample genes. It is suitable for detecting especially rare and polymicrobial infections. To our best knowledge, infection of Schizophyllum commune have not been reported in English literature with diagnostic method of mNGS.

Application of metagenomic next-generation sequencing in the diagnosis of pulmonary invasive fungal disease.

Background: Metagenomic next-generation sequencing (mNGS) is increasingly being used to detect pathogens directly from clinical specimens. However, the optimal application of mNGS and subsequent result interpretation can be challenging. In addition, studies reporting the use of mNGS for the diagnosis of invasive fungal infections (IFIs) are rare. Objective: We critically evaluated the performance of mNGS in the diagnosis of pulmonary IFIs, by conducting a multicenter retrospective analysis. The methodological strengths of mNGS were recognized, and diagnostic cutoffs were determined. Methods: A total of 310 patients with suspected pulmonary IFIs were included in this study. Conventional microbiological tests (CMTs) and mNGS were performed in parallel on the same set of samples. Receiver operating characteristic (ROC) curves were used to evaluate the performance of the logarithm of reads per kilobase per million mapped reads [lg(RPKM)], and read counts were used to predict true-positive pathogens. Result: The majority of the selected patients (86.5%) were immunocompromised. Twenty species of fungi were detected by mNGS, which was more than was achieved with standard culture methods. Peripheral blood lymphocyte and monocyte counts, as well as serum albumin levels, were significantly negatively correlated with fungal infection. In contrast, C-reactive protein and procalcitonin levels showed a significant positive correlation with fungal infection. ROC curves showed that mNGS [and especially lg(RPKM)] was superior to CMTs in its diagnostic performance. The area under the ROC curve value obtained for lg(RPKM) in the bronchoalveolar lavage fluid of patients with suspected pulmonary IFIs, used to predict true-positive pathogens, was 0.967, and the cutoff value calculated from the Youden index was -5.44. Conclusions: In this study, we have evaluated the performance of mNGS-specific indicators that can identify pathogens in patients with IFIs more accurately and rapidly than CMTs, which will have important clinical implications.

Progress and challenges in fungal lung disease in cystic fibrosis.

PURPOSE OF REVIEW: This review is an overview of the recent progress made for the diagnosis and understanding of fungal lung disease in people with cystic fibrosis (CF), with a focus on Aspergillus fumigatus , the most common filamentous fungus in the CF airway. Currently, the longstanding question of the clinical significance of Aspergillus fumigatus and other fungi in CF respiratory cultures, in the absence of allergy, remains. Clinical criteria and biomarkers are needed to classify fungal lung disease and determine who may warrant therapy. RECENT FINDINGS: Several retrospective and prospective studies have described the prevalence of A. fumigatus and other fungi in the CF lung and factors contributing to the changes in fungal epidemiology. Selective fungus culture testing for the detection of fungi in CF sputa has been well studied, yet a standardized fungus culture protocol has yet to be defined. Culture-independent molecular studies and other fungal diagnostic testing have been conducted in the CF population, leading to efforts to better understand the clinical role of these tests. Recent works have aimed to determine whether chronic A. fumigatus colonization is associated with lung disease progression measured by FEV 1 percentage predicted, structural lung disease, lung clearance index and respiratory quality-of-life. However, the existing knowledge gaps remain: definition of a fungal respiratory infection, the association between fungal infection and clinical outcomes, and indications for antifungal therapy. SUMMARY: Significant progress has been made for the detection and diagnosis of fungal lung disease. Yet, the role and impact of A. fumigatus and other fungal infections on respiratory health in people with CF remains to be determined.

Clinical Analysis of Non-AIDS Patients with Pulmonary Cryptococcosis and the Change in Their Clinical Features over 30 Years in a Tertiary Hospital in Beijing, China.

Over the past few decades, the clinical features of pulmonary cryptococcosis (PC) have progressed; however, there is a lack of data on the manifestations of PC over time. To investigate the differences in the clinical characteristics of PC across different time periods, we retrospectively reviewed 130 non-acquired immunodeficiency syndrome (AIDS) patients diagnosed with pathologically or microbiologically confirmed PC from 1990-2020. Among the 130 patients with PC, 24 (18.5%) exhibited immunosuppression, and 44 (33.8%) had underlying diseases. In radiology, 118 (90.8%) presented with subpleural lesions, and 68 (53.1%) presented with nodules with diameters ranging from 1-5 cm. Seventy-five (57.7%) patients underwent surgery alone. The clinical features of PC at different time periods showed that hospitalization days decreased (P = 0.009), and the number of patients with symptoms decreased over time. The number of patients exhibiting isolated lesions decreased (P = 0.022), and the number of patients exhibiting subpleural lesions increased (P = 0.020). In addition, the number of patients with lesions presenting 3-10 mm nodules increased (P = 0.028). In conclusion, an increasing number of patients have been diagnosed with PC over the last 30 years. The timing of PC diagnosis has shifted to the early stages of disease progression. Pulmonary lesions caused by cryptococcosis are easily misdiagnosed and may require unnecessary surgical treatment. Further research is needed to identify the lung lesions caused by cryptococcosis.

A case of pulmonary histoplasmosis treated with voriconazole.

Histoplasmosis is an infection caused by the dimorphic fungus Histoplasma capsulatum. The lungs are the most common site of infection, especially in patients with immune deficiency. We report a case of 62-year-old male patient presented with cough for 3 months and had been taking immunosuppressive drugs for 10 years after heart transplantation. Chest CT scan showed multiple pulmonary nodules. Lung tissue biopsy specimen culture suggested fungal infection, and Histoplasma capsulatum was confirmed by next-generation sequencing (NGS) detection. The patient was diagnosed with pulmonary histoplasmosis. After administration of voriconazole for 46 days, the symptom of cough was markedly relieved and the lesions were partly absorbed. After 13 months of treatment, the lesions completely disappeared, and no significant side-effect of voriconazole was observed. To our knowledge, report of voriconazole as the treatment of histoplasmosis is rare, especially in non-endemic areas. Moreover, this case enriches our experience in the adjustment between immunosuppressive and antifungal agents in treating histoplasmosis.

Outcomes after lung resection in renal transplant patients with pulmonary mucormycosis.

BACKGROUND: Pulmonary mucormycosis has been associated with high mortality (reported up to 100%) in renal transplant recipients. METHODS: This was a retrospective analysis of renal transplant patients with pulmonary mucormycosis between April 2014 and March 2020, who underwent surgical resection of the affected lung along with liposomal amphotericin therapy. Patients with lower respiratory illness features underwent chest X-ray, high-resolution computed tomography of the chest, and those with suspicious findings underwent analysis of bronchioloalveolar fluid and transbronchial lung biopsy. Patients with histological or microbiological evidence of mucormycosis were started on liposomal Amphotericin B. Tacrolimus and mycophenolate mofetil were stopped at the time of diagnosis. RESULT: Ten patients underwent combined management, while five patients were managed medically. At last follow up, seven out of ten patients (70%) who underwent combined management and two of the five patients (40%) who were managed medically, had a mean survival of 28.86 months (sd = 15.71, median = 25) and 14.17 months (sd = 12.21, median = 18), respectively, post-diagnosis of pulmonary mucormycosis. CONCLUSION: Surgical resection combined with antifungals in the perioperative period and decreased immunosuppression may improve the outcomes in renal transplant patients with pulmonary mucormycosis.

Malignant melanoma mimic fungal infection a case report.

BACKGROUND: Most of malignant melanomas originate from skin and often metastasize to the lungs, rarely metastasizes to the liver and bone. However, imageology characters of lung metastasis tumor are commonly similar to those of fungal infections. CASE PRESENTATION: A patient was admitted with unhealed plantar puncture wound for 3 years, and cough and expectoration for 2 years. The chest computed tomography (CT) revealed multiple nodules with cavities, and the patient was diagnosed of pulmonary fungal infection in another hospital and received antifungal therapy for more than 8 months, but the clinical symptoms and chest imaging findings continue to progress. After admission, the pathological results of both lung biopsy and biopsy of the plantar wound 3 years ago indicated malignant melanoma. CONCLUSIONS: The diagnosis of lung lesions cannot rely solely on imaging diagnosis, lung biopsy should be performed if necessary.

The lung microbiome in end-stage Lymphangioleiomyomatosis.

Lymphangioleiomyomatosis (LAM) is a progressive cystic lung disease with mortality driven primarily by respiratory failure. Patients with LAM frequently have respiratory infections, suggestive of a dysregulated microbiome. Here we demonstrate that end-stage LAM patients have a distinct microbiome signature compared to patients with end-stage chronic obstructive pulmonary disease.

A 34-Year-Old Man With HIV/AIDS and a Cavitary Pulmonary Lesion.

A 34-year-old man presented to a community hospital with fever and fatigue for 3 days and was found to be febrile and tachycardic with a cavitary pulmonary lesion and paratracheal adenopathy on CT imaging. One month before, he had presented to his primary care provider with a palmar rash; he had been diagnosed and treated for syphilis and was also diagnosed with HIV. He had a CD4 count of 106 cells/µL and an HIV viral load of 1,290,000 copies/mL. Pneumocystis prophylaxis with trimethoprim-sulfamethoxazole and antiretroviral treatment with only tenofovir and emtricitabine therapy were started 2 weeks before presentation.

Pulmonary nodule in pediatrics: Beyond the infection. / Nódulo pulmonar en pediatría: Más allá de la infección.

INTRODUCTION: The study of a pulmonary nodule in pediatrics is a diagnostic challenge where multiple pathologies must be taken into account, especially infections. In developing countries, where tuberculosis infec tion is endemic, it is one of the most likely diagnoses; however, the diagnostic possibility of malig nancy should never be overlooked. OBJECTIVE: To describe a case report of a patient with a pulmonary nodule, that after ruling out the most frequent causes, a primary malignant tumor was diagnosed. CLINICAL CASE: 17-year-old female patient with a one-month history of cough, dyspnea, and hemop tysis, without other symptoms. Since she did not respond to conventional antibiotic management, a chest CT scan with contrast was performed which showed a pulmonary nodule with irregular con tours, and with the bronchoalveolar lavage pulmonary infections were ruled out (pulmonary tuber culosis, fungal infection, and others bacteria). Biopsy of the lesion was performed to complete the study which histopathology was compatible with a mucoepidermoid carcinoma (MEC). The patient underwent right low lobectomy and lymph node resection with good clinical response during three years of follow-up. CONCLUSION: Pulmonary nodule in pediatrics is a finding usually associated with infection, nevertheless, neoplastic conditions have to be considered, not only metastasis but also pri mary pulmonary malignant lesions due to prognosis implications.

Case Report: A Great Mimicker of Neoplasm: Pulmonary Cryptococcosis in an Immunocompetent Host After High-Altitude Descent.

Cryptococcus exposure in certain global regions is common and yet virulence in the immunocompetent host remains rare. Radiological findings of pulmonary cryptococcosis may include nonspecific lung nodules or masses indistinguishable from lung cancer or pulmonary tuberculosis. We present a case of an immunocompetent diabetic female who presented with progressively worsening pleuritic chest pain and cough with travel between Tibet and New York 2 months earlier. Chest imaging demonstrated a large lobulated mass, acid-fast bacillus smears were negative, and our patient underwent pulmonary biopsy, which grew rare budding yeast later confirmed by mucicarmine staining as Cryptococcus. Our patient was successfully treated with fluconazole therapy. We hypothesize that the high altitude of Tibet may allow for clinical latency followed by symptomatic reactivation on descent. A raised index of suspicion for pulmonary cryptococcosis with careful attention to travel history is expected to facilitate timely diagnosis.

Pneumonia and Poorly Controlled Diabetes.

CASE PRESENTATION: A 47-year-old man with poorly controlled diabetes mellitus (glycosylated hemoglobin 12%) presented to the ED with a 1-week history of fevers, productive cough, and dyspnea. The patient was febrile and hypoxemic on presentation; laboratory testing was remarkable for hyperglycemia and ketoacidosis. The initial chest CT scan showed right lower lobe consolidation and ground-glass opacities (Fig 1A). He was admitted to the ICU and administered IV antibiotics (cefepime and vancomycin) for the treatment of community-acquired bacterial pneumonia.

Pulmonary infection with Penicillium citrinum in a patient with multiple myeloma.

A 60-year-old male patient undergoing chemotherapy for multiple myeloma Stage II presented to our hospital with complaints of cough, haemoptysis, fever and loose stools. Sputum sample was sent for fungal culture. Fungal culture on Sabouraud dextrose agar yielded bluish-green velvety growth with orange-to-red diffusible pigment on the reverse. The isolate was identified as Penicillium species, probably Penicillium citrinum or Penicillium pinophilus. As the isolate did not exhibit thermal dimorphism, the possibility of the fungal isolate being Penicillium marneffei was ruled out. The isolate was sent for molecular identification and confirmation, which was identified as P. citrinum. His HIV status was negative. In this case, his immunocompromised state due to multiple myeloma and chemotherapy could have predisposed him to this fungal infection, which is an emerging infection and a rare manifestation seen in high-risk patients receiving targeted therapies.

Exacerbation of pulmonary cryptococcosis associated with enhancement of Th2 response in the postpartum period.

Cryptococcosis is an invasive mycosis that has become increasingly prevalent in immunocompromised patients. Pregnant women are also one of the risk populations for cryptococcosis. Reversal of Th2 to Th1 response following resolution of immunosuppression during the postpartum period can lead to overt clinical manifestations of a previously silent infection, resembling an immune reconstitution inflammatory syndrome. Here, we report a case of a 30-year-old woman who had an exacerbation of pulmonary cryptococcosis in the postpartum period mimicking an immune reconstitution inflammatory syndrome. In the present case, chest computed tomography showed multiple small nodules on the day of the delivery; however, pulmonary cryptococcosis, which was subclinical during pregnancy, rapidly worsened to mass-like consolidation at one month after the delivery. Pathohistological examination of the lung specimen showed lung parenchyma infiltration with histiocytes and numerous lymphocytes without granulomatous formations, and a small number of yeast-like organisms consistent with Cryptococcus without capillary involvement. Immunohistochemical staining showed predominance of CD3+ cells and CD4+ cells over CD8+ cells. In addition, GATA3+ cells dominated over T-bet + cells. These data suggested exacerbation of pulmonary cryptococcosis associated with enhancement of Th2 response in the postpartum period.

An unusual case of reactivated latent pulmonary cryptococcal infection in a patient after short-term steroid and azathioprine therapy: a case report.

BACKGROUND: Cryptococcus is one of the major fungal pathogens infecting the lungs. Pulmonary cryptococcal infection is generally considered a community-acquired condition caused by inhalation of dust contaminated with fungal cells from the environment. Here, we report a case developing pulmonary cryptococcosis 3 months after hospital admission, which has rarely been reported before. CASE PRESENTATION: A 73-year-old female patient who was previously immunocompetent experienced persistent dry cough for 2 weeks, 3 months after admission. Chest computed tomography (CT) showed a new solitary pulmonary nodule developed in the upper lobe of the left lung. Staining and culture of expectorated sputum smears were negative for bacteria, acid-fast bacilli, or fungus. The patient then underwent biopsy of the lesion. Histopathology findings and a positive serum cryptococcal antigen titer (1:8) indicated pulmonary cryptococcosis. Daily intravenous 400 mg fluconazole was administered initially followed by oral fluconazole therapy. Follow-up chest CT after 3 months of antifungal therapy showed complete disappearance of the pulmonary nodule. Respiratory symptoms of the patient also resolved. A complete investigation excluded the possibility of a patient-to-patient transmission or primarily acquiring the infection from the hospital environment. Based on the patient's history of exposure to pigeons before admission and recent steroid and azathioprine use after admission for the treatment of myasthenic crisis, reactivation of a latent pulmonary cryptococcal infection acquired before admission, in this case, is impressed. CONCLUSIONS: Although rarely reported, pulmonary cryptococcal infection should be included in the differential diagnosis of hospitalized patients with respiratory symptoms, especially in those with predisposing risk factors. Chest image studies and further surgical biopsy are needed for confirmation.