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Wang S, Liu Y, Hu L, Qian G, Mo Y. Case Report: Pulmonary mucormycosis caused by Rhizopus microsporus in a patient with chronic obstructive pulmonary disease. Front Med (Lausanne) 2025; 12:1544621. [PMID: 40270499 PMCID: PMC12014429 DOI: 10.3389/fmed.2025.1544621] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2024] [Accepted: 03/20/2025] [Indexed: 04/25/2025] Open
Abstract
Background We report a rare case of pulmonary mucormycosis caused by Rhizopus microsporus, which is rare in patients with chronic obstructive pulmonary disease. Rhizopus microsporus had been reported as the most common etiological agent associated with human infections, except Rhizopus oryzae in some studies. Case presentation We described a case of 81-year-old man with pulmonary mucormycosis caused by Rhizopus microsporus but no other apparent risk factors including diabetes. The diagnosis mainly relied on sputum cultures and clinical manifestations. Despite antifungal therapy, his condition worsened, resulting in mortality. Conclusion In this case, the patient had no underlying diseases such as diabetes or solid tumors. Clinicians should be aware of routine pathogenic microbiological tests of pulmonary mucormycosis in patients with chronic obstructive pulmonary disease. Early and aggressive treatment can lead to improved prognosis.
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Affiliation(s)
- Shanshan Wang
- Department of Laboratory Medicine, The First Affiliated Hospital of Ningbo University, Ningbo, China
| | - Yanqing Liu
- Department of Laboratory Medicine, The First Affiliated Hospital of Ningbo University, Ningbo, China
| | - Liqing Hu
- Department of Laboratory Medicine, The First Affiliated Hospital of Ningbo University, Ningbo, China
| | - Guoqing Qian
- Department of Infectious Diseases, The First Affiliated Hospital of Ningbo University, Ningbo, China
| | - Yijun Mo
- Department of Laboratory Medicine, The First Affiliated Hospital of Ningbo University, Ningbo, China
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2
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Evans TJ, Lawal A, Kosmidis C, Denning DW. Chronic Pulmonary Aspergillosis: Clinical Presentation and Management. Semin Respir Crit Care Med 2024; 45:88-101. [PMID: 38154471 DOI: 10.1055/s-0043-1776914] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2023]
Abstract
Chronic pulmonary aspergillosis (CPA) refers to a number of clinical syndromes resulting from the presence and local proliferation of Aspergillus organisms in the lungs of patients with chronic lung disease. CPA is more common than was realized two decades ago. Recognition remains poor, despite recent studies from many countries highlighting the high prevalence in at-risk populations. In low- and middle-income countries, CPA may be misdiagnosed and treated as tuberculosis (TB). In addition, CPA may develop following successful TB treatment. The coronavirus disease pandemic has resulted in significant disruption to provision of TB care, likely leading to more extensive lung damage, which could increase the risk for CPA.Although CPA refers to various syndromes, the classic presentation is that of chronic cavitary pulmonary aspergillosis, which manifests as one or more progressive cavities with or without a fungal ball, accompanied by systemic and respiratory symptoms for at least 3 months. Diagnosis relies on Aspergillus immunoglobulin G in serum, as sputum culture lacks sensitivity. Differential diagnosis includes mycobacterial infection, bacterial lung abscess or necrotizing pneumonia, lung cancer, and endemic fungi.The aim of antifungal treatment in CPA is to improve symptoms and quality of life, and to halt progression, and possibly reverse radiological changes. Current recommendations suggest treatment for 6 months, although in practice many patients remain on long-term treatment. Improvement may manifest as weight gain and improvement of symptoms such as productive cough, hemoptysis, and fatigue. Surgical management should be considered in cases of diagnostic uncertainty, in significant hemoptysis, and when there is concern for lack of response to therapy. Itraconazole and voriconazole are the first-line azoles, with more experience now accumulating with posaconazole and isavuconazole. Side effects are frequent and careful monitoring including therapeutic drug monitoring is essential. Intravenous antifungals such as echinocandins and amphotericin B are used in cases of azole intolerance or resistance, which often develop on treatment. Relapse is seen after completion of antifungal therapy in around 20% of cases, mostly in bilateral, high-burden disease.Several research priorities have been identified, including characterization of immune defects and genetic variants linked to CPA, pathogenetic mechanisms of Aspergillus adaptation in the lung environment, the contribution of non-fumigatus Aspergillus species, and the role of new antifungal agents, immunotherapy, and combination therapy.
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Affiliation(s)
- Terry J Evans
- Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit, Mahosot Hospital, Vientiane, Lao PDR
| | - AbdulAzeez Lawal
- National Aspergillosis Centre, Wythenshawe Hospital, Manchester University Foundation Trust, Manchester, United Kingdom
| | - Chris Kosmidis
- National Aspergillosis Centre, Wythenshawe Hospital, Manchester University Foundation Trust, Manchester, United Kingdom
- Manchester Fungal Infection Group, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Manchester, United Kingdom
| | - David W Denning
- Manchester Fungal Infection Group, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Manchester, United Kingdom
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3
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Hamdar H, Nahle AA, Jaber R, Salame H, Sikaria A, Souleiman Y. Pulmonary pseudoaneurysm in the setting of concurrent COVID-19 and pulmonary mucormycosis: A rare case report. Clin Case Rep 2023; 11:e7947. [PMID: 37744631 PMCID: PMC10517220 DOI: 10.1002/ccr3.7947] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2023] [Revised: 07/26/2023] [Accepted: 09/12/2023] [Indexed: 09/26/2023] Open
Abstract
Key Clinical Message This case illustrates the possible danger of PAP emergence in individuals with a confluence of conditions capable of inducing vascular impairment, like COVID-19, pulmonary mucormycosis (PM), and diabetes. Abstract Pulmonary mucormycosis (PM) is a highly lethal invasive infection. It is a rare complication of COVID-19 and is associated with a high mortality rate. Pulmonary pseudoaneurysm (PAP) is a severe manifestation of this condition, often resulting in death. Management involves endovascular therapy followed by surgery and appropriate antifungal treatment.
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Affiliation(s)
| | | | - Rida Jaber
- Faculty of MedicineDamascus UniversityDamascusSyria
| | - Hadi Salame
- Faculty of MedicineDamascus UniversityDamascusSyria
| | | | - Younes Souleiman
- Department of Thoracic SurgeryAlassad University HospitalDamascusSyria
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Guo XZ, Gong LH, Wang WX, Yang DS, Zhang BH, Zhou ZT, Yu XH. Chronic pulmonary mucormycosis caused by rhizopus microsporus mimics lung carcinoma in an immunocompetent adult: A case report. World J Clin Cases 2023; 11:3295-3303. [PMID: 37274035 PMCID: PMC10237139 DOI: 10.12998/wjcc.v11.i14.3295] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2023] [Revised: 04/02/2023] [Accepted: 04/12/2023] [Indexed: 05/16/2023] Open
Abstract
BACKGROUND Pulmonary mucormycosis is a rare but life-threatening invasive fungal infection that mostly affects immunocompromised patients. This disease usually develops acutely and progresses rapidly, often leading to a poor clinical prognosis. Chronic pulmonary mucormycosis is highly unusual in immunocompetent patients.
CASE SUMMARY A 43-year-old man, who was a house improvement worker with a long history of occupational dust exposure, presented with an irritating cough that had lasted for two months. The patient was previously in good health, without dysglycemia or any known immunodeficiencies. Chest computed tomography revealed a mass in the left lower lobe, measuring approximately 6 cm in diameter, which was suspected to be primary lung carcinoma complicated with obstructive pneumonia. Thoracoscopic-assisted left lower lobectomy was performed, and metagenomic next-generation sequencing detection, along with special pathological staining of surgical specimens, suggested Rhizopus microsporus infection. Postoperatively, the patient's respiratory symptoms were relieved, and no signs of recurrence were found during the six-month follow-up.
CONCLUSION This article reports a rare case of chronic pulmonary mucormycosis caused by Rhizopus microsporus in a middle-aged male without dysglycemia or immunodeficiency. The patient's surgical outcome was excellent, reaffirming that surgery remains the cornerstone of pulmonary mucormycosis treatment.
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Affiliation(s)
- Xing-Zi Guo
- Department of Gynecologic Oncology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410031, Hunan Province, China
| | - Liang-Hui Gong
- The Second Department of Thoracic Surgery, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410031, Hunan Province, China
| | - Wen-Xiang Wang
- The Second Department of Thoracic Surgery, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410031, Hunan Province, China
| | - De-Song Yang
- The Second Department of Thoracic Surgery, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410031, Hunan Province, China
| | - Bai-Hua Zhang
- The Second Department of Thoracic Surgery, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410031, Hunan Province, China
| | - Ze-Tao Zhou
- GZMU-GIBH School of Life Sciences, Guangzhou Medical University, Guangzhou 511436, Guangdong Province, China
| | - Xiao-Hui Yu
- Department of Pathology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410031, Hunan Province, China
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Muthu V, Agarwal R, Patel A, Kathirvel S, Abraham OC, Aggarwal AN, Bal A, Bhalla AS, Chhajed PN, Chaudhry D, Garg M, Guleria R, Krishnan RG, Kumar A, Maheshwari U, Mehta R, Mohan A, Nath A, Patel D, Rudramurthy SM, Saxena P, Sethuraman N, Singhal T, Soman R, Thangakunam B, Varghese GM, Chakrabarti A. Definition, diagnosis, and management of COVID-19-associated pulmonary mucormycosis: Delphi consensus statement from the Fungal Infection Study Forum and Academy of Pulmonary Sciences, India. THE LANCET. INFECTIOUS DISEASES 2022; 22:e240-e253. [PMID: 35390293 PMCID: PMC8979562 DOI: 10.1016/s1473-3099(22)00124-4] [Citation(s) in RCA: 52] [Impact Index Per Article: 17.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/06/2022] [Revised: 02/03/2022] [Accepted: 02/03/2022] [Indexed: 12/16/2022]
Abstract
COVID-19-associated pulmonary mucormycosis (CAPM) remains an underdiagnosed entity. Using a modified Delphi method, we have formulated a consensus statement for the diagnosis and management of CAPM. We selected 26 experts from various disciplines who are involved in managing CAPM. Three rounds of the Delphi process were held to reach consensus (≥70% agreement or disagreement) or dissensus. A consensus was achieved for 84 of the 89 statements. Pulmonary mucormycosis occurring within 3 months of COVID-19 diagnosis was labelled CAPM and classified further as proven, probable, and possible. We recommend flexible bronchoscopy to enable early diagnosis. The experts proposed definitions to categorise dual infections with aspergillosis and mucormycosis in patients with COVID-19. We recommend liposomal amphotericin B (5 mg/kg per day) and early surgery as central to the management of mucormycosis in patients with COVID-19. We recommend response assessment at 4-6 weeks using clinical and imaging parameters. Posaconazole or isavuconazole was recommended as maintenance therapy following initial response, but no consensus was reached for the duration of treatment. In patients with stable or progressive disease, the experts recommended salvage therapy with posaconazole or isavuconazole. CAPM is a rare but under-reported complication of COVID-19. Although we have proposed recommendations for defining, diagnosing, and managing CAPM, more extensive research is required.
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Affiliation(s)
- Valliappan Muthu
- Department of Pulmonary Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Ritesh Agarwal
- Department of Pulmonary Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Atul Patel
- Department of Infectious Diseases, Sterling Hospital, Ahmedabad, India
| | - Soundappan Kathirvel
- Department of Community Medicine and School of Public Health, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | | | - Ashutosh Nath Aggarwal
- Department of Pulmonary Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Amanjit Bal
- Department of Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Ashu Seith Bhalla
- Department of Radiodiagnosis, All India Institute of Medical Sciences, New Delhi, India
| | - Prashant N Chhajed
- Department of Pulmonary Medicine, Institute of Pulmonology, Medical Research and Development, Mumbai, India
| | - Dhruva Chaudhry
- Department of Pulmonary Medicine, Pandit Bhagwat Dayal Sharma Postgraduate Institute of Medical Sciences, Rohtak, India
| | - Mandeep Garg
- Department of Radiodiagnosis and Imaging, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Randeep Guleria
- Department of Pulmonary Medicine, All India Institute of Medical Sciences, New Delhi, India
| | | | - Arvind Kumar
- Department of Thoracic Surgery, Medanta Hospital, Gurgaon, India
| | - Uma Maheshwari
- Department of Pulmonary Medicine, St John's Hospital, Bengaluru, India
| | - Ravindra Mehta
- Department of Pulmonary Medicine, Apollo Hospitals, Bengaluru, India
| | - Anant Mohan
- Department of Pulmonary Medicine, All India Institute of Medical Sciences, New Delhi, India
| | - Alok Nath
- Department of Pulmonary Medicine, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India
| | - Dharmesh Patel
- Department of Pulmonary Medicine, City Clinic and Bhailal Amin General Hospital, Vadodara, India
| | | | - Puneet Saxena
- Department of Pulmonary Medicine, Army Hospital Research and Referral, New Delhi, India
| | | | - Tanu Singhal
- Department of Infectious Diseases, Kokilaben Dhirubhai Ambani Hospital and Medical Research Institute, Mumbai, India
| | - Rajeev Soman
- Department of Infectious Diseases, Jupiter Hospital, Pune, India
| | | | - George M Varghese
- Department of Internal Medicine, Christian Medical College, Vellore, India
| | - Arunaloke Chakrabarti
- Department of Medical Microbiology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
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Azhar A, Khan WH, Khan PA, Alhosaini K, Owais M, Ahmad A. Mucormycosis and COVID-19 pandemic: Clinical and diagnostic approach. J Infect Public Health 2022; 15:466-479. [PMID: 35216920 PMCID: PMC8855610 DOI: 10.1016/j.jiph.2022.02.007] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2021] [Revised: 02/08/2022] [Accepted: 02/17/2022] [Indexed: 01/08/2023] Open
Abstract
The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is yet to be controlled worldwide, especially in India. The second wave of coronavirus disease 2019 (COVID-19) led to panic and confusion in India, owing to the overwhelming number of the population that fell prey to this highly infectious virus of recent times. In the second wave of COVID-19, the patients had to fight both the virus and opportunistic infections triggered by fungi and bacteria. Repeated use of steroids, antibiotics, and oxygen masks during the management of severely and critically ill COVID-19 patients nurtured opportunistic infections such as mucormycosis. Despite mucormycosis being a decades-old disease, it has gained notice of its widespread occurrence in COVID-19 patients throughout India. Instances of mucormycosis are usually unearthed in immunocompromised individuals and are caused by the inhalation of filamentous fungi, either from the natural environment or through supportive care units. In the recent outbreak during the second wave of COVID-19 in India, it has been seen to cause secondary infection as it grows along with the treatment of COVID-19. Furthermore, COVID-19 patients with comorbidities such as diabetes were more likely to have the mucormycosis co-infection because of their challenged immune systems' inability to fight it. Despite the hype, mucormycosis still remains neglected and least studied, which is predominantly due to all focus on diagnostics, vaccine, and therapeutic research. In this review, we emphasize mainly on the association of mucormycosis in COVID-19 patients. We also present the molecular mechanism of mucormycosis for a better understanding of the fungal infections in patients who have recently been infected with SARS-CoV-2. Better understanding of fungal pathogens, immediate diagnosis, and management of the infections are crucial in COVID-19 patients, as high mortalities have been recorded in co-infected patients despite recovery from COVID-19.
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Affiliation(s)
- Asim Azhar
- Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, Uttar Pradesh, India.
| | - Wajihul Hasan Khan
- Department of Chemical Engineering, Indian Institute of Technology Delhi, New Delhi, India; Department of Microbiology, All India Institute of Medical Sciences, New Delhi, India
| | - Parvez Anwar Khan
- Department of Microbiology, Jawaharlal Nehru Medical College, Aligarh Muslim University Aligarh, Uttar Pradesh, India
| | - Khaled Alhosaini
- Department of Pharmacology & Toxicology, College of Pharmacy, King Saud University, Post Box 2457, Riyadh 11451, Saudi Arabia
| | - Mohammad Owais
- Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, Uttar Pradesh, India
| | - Aijaz Ahmad
- Clinical Microbiology and Infectious Diseases, School of Pathology, Health Sciences, University of the Witwatersrand, Johannesburg 2193, South Africa; Infection Control, Charlotte Maxeke Johannesburg Academic Hospital, National Health Laboratory Service, Johannesburg 2193, South Africa.
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7
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Jethani V, Sharma D, Pant S, Joshi S. Pulmonary mucormycosis: a rare case report. THE JOURNAL OF ASSOCIATION OF CHEST PHYSICIANS 2022. [DOI: 10.4103/jacp.jacp_7_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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Rajaa S, Krishnamoorthy Y, Knudsen S, Roy G, Ellner J, Horsburgh CR, Hochberg NS, Salgame P, S G, Prakash Babu S, Sarkar S. Prevalence and factors associated with diabetes mellitus among tuberculosis patients in South India-a cross-sectional analytical study. BMJ Open 2021; 11:e050542. [PMID: 34686553 PMCID: PMC8543642 DOI: 10.1136/bmjopen-2021-050542] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2021] [Accepted: 09/30/2021] [Indexed: 12/13/2022] Open
Abstract
OBJECTIVE To determine the prevalence and determinants of diabetes mellitus (DM) among tuberculosis (TB) patients and to assess the additional yield and number needed to screen (NNS) to obtain a newly diagnosed DM among TB patients. DESIGN We undertook a cross-sectional analysis of the cohort data under Regional Prospective Observational Research for Tuberculosis-India consortium. Newly diagnosed TB patients recruited into the cohort between 2014 and 2018 were included. Pretested standardised questionnaires and tools were used for data collection. Prevalence of DM among TB patients was summarised as proportion with 95% CI. Type II DM was diagnosed if random blood sugar level was >200 mg/dL or if the participant had a documented history of DM. NNS by blood glucose testing to diagnose one new DM case among TB patients was also calculated. SETTING Three districts of South India: Puducherry, Cuddalore and Villupuram SUBJECTS: Newly diagnosed sputum smear positive pulmonary TB patients aged ≥16 years RESULTS: In total, 1188 TB patients were included. Prevalence of DM among TB patients was 39% (95% CI: 36.2% to 41.8%). In unadjusted analysis, elderly TB, marital status, caste, gender, higher education level, household income and obesity had a significant association with DM. However, in adjusted analysis, only marital status (currently married aPR; 3.77 (95 CI: 2.20 to 6.49), widowed/separated/divorced aPR; 3.66 (95 CI: 1.96 to 6.83)) and body mass index category (normal weight aPR; 3.26 (95 CI: 2.55 to 4.16), overweight aPR; 3.86 (95 CI: 2.69 to 5.52), obesity aPR; 4.08 (95 CI: 2.81 to 5.94)) were found to be significant determinants. The number of TB patients needed to be screened to find a new DM case was 12. CONCLUSION We found that one in three TB patients had coexisting DM. The number of TB patients needed to be screened to obtain a newly diagnosed DM patients was also determined. The study supports and highlights the need of RNTCP's effort in bidirectional screening of TB and DM.
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Affiliation(s)
- Sathish Rajaa
- Jawaharlal Institute of Postgraduate Medical Education, Puducherry, India
| | | | - Selby Knudsen
- Department of Infectious Diseases, Boston Medical Center, Boston, Massachusetts, USA
| | - Gautam Roy
- Department of Preventive and Social Medicine, Jawaharlal Institute of Post Graduate Medical Education and Research, Puducherry, Puducherry, India
| | - Jerrold Ellner
- Department of Medicine, Rutgers New Jersey Medical School, Newark, New Jersey, USA
| | | | - Natasha S Hochberg
- Section of Infectious Diseases, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA
- Department of Epidemiology, Boston University School of Public Health, Boston, Massachusetts, USA
| | | | - Govindarajan S
- Directorate of Health Services, State TB cell, Puducherry, India
| | - Senbagavalli Prakash Babu
- Department of Preventive and Social Medicine, Jawaharlal Institute of Post Graduate Medical Education and Research, Puducherry, Puducherry, India
| | - Sonali Sarkar
- Department of Preventive and Social Medicine, Jawaharlal Institute of Post Graduate Medical Education and Research, Puducherry, Puducherry, India
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Sahu RK, Salem-Bekhit MM, Bhattacharjee B, Almoshari Y, Ikbal AMA, Alshamrani M, Bharali A, Salawi A, Widyowati R, Alshammari A, Elbagory I. Mucormycosis in Indian COVID-19 Patients: Insight into Its Patho-Genesis, Clinical Manifestation, and Management Strategies. Antibiotics (Basel) 2021; 10:1079. [PMID: 34572661 PMCID: PMC8468123 DOI: 10.3390/antibiotics10091079] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2021] [Revised: 08/23/2021] [Accepted: 08/24/2021] [Indexed: 12/21/2022] Open
Abstract
Mucormycosis in patients who have COVID-19 or who are otherwise immunocompromised has become a global problem, causing significant morbidity and mortality. Infection is debilitating and fatal, leading to loss of organs and emotional trauma. Radiographic manifestations are not specific, but diagnosis can be made through microscopic examination of materials collected from necrotic lesions. Treatment requires multidisciplinary expertise, as the fungus enters through the eyes and nose and may even reach the brain. Use of the many antifungal drugs available is limited by considerations of resistance and toxicity, but nanoparticles can overcome such limitations by reducing toxicity and increasing bioavailability. The lipid formulation of amphotericin-B (liposomal Am-B) is the first-line treatment for mucormycosis in COVID-19 patients, but its high cost and low availability have prompted a shift toward surgery, so that surgical debridement to remove all necrotic lesions remains the hallmark of effective treatment of mucormycosis in COVID-19. This review highlights the pathogenesis, clinical manifestation, and management of mucormycosis in patients who have COVID-19.
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Affiliation(s)
- Ram Kumar Sahu
- Department of Pharmaceutical Science, Faculty of Pharmacy, Universitas Airlangga, Surabaya 60115, Indonesia; (R.K.S.); (R.W.)
- Department of Pharmaceutical Science, Assam University (A Central University), Silchar 788011, India
| | - Mounir M. Salem-Bekhit
- Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
- Department of Microbiology and Immunology, Faculty of Pharmacy, Al-Azhar University, Cairo 11884, Egypt
| | - Bedanta Bhattacharjee
- Department of Pharmaceutical Sciences, Faculty of Science and Engineering, Dibrugarh University, Dibrugarh 786004, India;
| | - Yosif Almoshari
- Department of Pharmaceutics, College of Pharmacy, Jazan University, Jazan 45142, Saudi Arabia; (Y.A.); (M.A.); (A.S.)
| | - Abu Md Ashif Ikbal
- Department of Pharmacy, Tripura University (A Central University), Suryamaninagar 799022, India
| | - Meshal Alshamrani
- Department of Pharmaceutics, College of Pharmacy, Jazan University, Jazan 45142, Saudi Arabia; (Y.A.); (M.A.); (A.S.)
| | - Alakesh Bharali
- Department of Pharmaceutics, Girijananda Chowdhury Institute of Pharmaceutical Sciences, Azara, Hatkhowapara, Guwahati 781017, India;
| | - Ahmad Salawi
- Department of Pharmaceutics, College of Pharmacy, Jazan University, Jazan 45142, Saudi Arabia; (Y.A.); (M.A.); (A.S.)
| | - Retno Widyowati
- Department of Pharmaceutical Science, Faculty of Pharmacy, Universitas Airlangga, Surabaya 60115, Indonesia; (R.K.S.); (R.W.)
| | - Abdulrahman Alshammari
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia;
| | - Ibrahim Elbagory
- College of Pharmacy, Northern Border University, Arar 1321, Saudi Arabia;
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Ukoha CD, Nguyen N. Pulmonary Mucormycosis: An Interesting Case of Rhizopus Mucormycosis. Cureus 2021; 13:e16210. [PMID: 34262833 PMCID: PMC8260200 DOI: 10.7759/cureus.16210] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/06/2021] [Indexed: 11/05/2022] Open
Abstract
We report a case of a 57-year-old Vietnamese gentleman who presented with chest pain and shortness of breath for four weeks. The patient had a history of diabetes mellitus and kidney transplant in the past year and was currently on immunosuppressive agents. The patient's condition worsened despite broad-spectrum antibiotics, so amphotericin was added. Further evaluation with bronchoscopy and transbronchial biopsy was suggestive of Rhizopus mucormycosis. Despite antifungal therapy, his condition worsened, resulting in multi-organ failure and eventual mortality.
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Affiliation(s)
| | - Nicholas Nguyen
- Internal Medicine, Methodist Dallas Medical Center, Dallas, USA
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11
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Nguyen NTB, Le Ngoc H, Nguyen NV, Dinh LV, Nguyen HV, Nguyen HT, Denning DW. Chronic Pulmonary Aspergillosis Situation among Post Tuberculosis Patients in Vietnam: An Observational Study. J Fungi (Basel) 2021; 7:532. [PMID: 34209322 PMCID: PMC8307285 DOI: 10.3390/jof7070532] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2021] [Revised: 06/25/2021] [Accepted: 06/28/2021] [Indexed: 12/28/2022] Open
Abstract
This study provides a brief view of chronic pulmonary aspergillosis (CPA) in the post-tuberculosis treatment community in Vietnam, a high burden tuberculosis (TB) country. In three months in late 2019, 70 post-TB patients managed at Vietnam National Lung Hospital were enrolled. Of these, 38 (54.3%) had CPA. The male/female ratio was 3/1 (28 males and ten females). CPA patients had a mean age of 59 ± 2.3 years (95%CI 54.4-63.6). The mean Body mass index (BMI) was 19.0 ± 0.5 (18.0-20.0) and 16 of 38 (42.1%) patients had concurrent diseases, the most common of which were chronic obstructive pulmonary disease (COPD) and diabetes. Twenty-six patients (68.4%) developed hemoptysis, 21 (55.3%) breathlessness, and weight loss was seen in 30 (78.9%). Anaemia was seen in 15 (39.5%) and 27 of 38 (71.1%) patients had an elevated C-reactive protein (CRP). The most common radiological findings were multiple cavities (52.6%) and pleural thickening (42.7%), followed by aspergilloma (29.0%) and non-specific infiltrates. There were five of 38 patients (13.2%) with a cavity containing a fungal ball on the chest X-ray, but when the high resolution computed tomography (HRCT) was examined, the number of patients with fungal balls rose to 11 (28.9%). Overall, 34 of 38 (89.5%) cases had an elevated Aspergillus IgG with an optical density ≥ 1, and in 2 cases, it was 0.9-1.0 (5%), borderline positive. In nine patients (23.7%) Aspergillus fumigatus was cultured from sputum. CPA is an under-recognised problem in Vietnam and other high burden TB countries, requiring a different diagnostic approach and treatment and careful management. HRCT and Aspergillus IgG serum test are recommended as initial diagnostic tools for CPA diagnosis.
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Affiliation(s)
- Ngoc Thi Bich Nguyen
- Vietnam National Lung Hospital, Hanoi 10000, Vietnam; (N.V.N.); (L.V.D.); (H.V.N.); (H.T.N.)
| | - Huy Le Ngoc
- Vietnam National Lung Hospital, Hanoi 10000, Vietnam; (N.V.N.); (L.V.D.); (H.V.N.); (H.T.N.)
| | - Nhung Viet Nguyen
- Vietnam National Lung Hospital, Hanoi 10000, Vietnam; (N.V.N.); (L.V.D.); (H.V.N.); (H.T.N.)
| | - Luong Van Dinh
- Vietnam National Lung Hospital, Hanoi 10000, Vietnam; (N.V.N.); (L.V.D.); (H.V.N.); (H.T.N.)
| | - Hung Van Nguyen
- Vietnam National Lung Hospital, Hanoi 10000, Vietnam; (N.V.N.); (L.V.D.); (H.V.N.); (H.T.N.)
| | - Huyen Thi Nguyen
- Vietnam National Lung Hospital, Hanoi 10000, Vietnam; (N.V.N.); (L.V.D.); (H.V.N.); (H.T.N.)
| | - David W. Denning
- Manchester Academic Health Science Centre, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M23 9LT, UK
- Global Action Fund for Fungal Infections, 1208 Geneva, Switzerland
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Zhou Y, Cheng L, Liao B, Shi Y, Niu Y, Zhu C, Ye X, Zhou X, Ren B. Candida albicans CHK1 gene from two-component system is essential for its pathogenicity in oral candidiasis. Appl Microbiol Biotechnol 2021; 105:2485-2496. [PMID: 33635358 DOI: 10.1007/s00253-021-11187-0] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2021] [Revised: 02/08/2021] [Accepted: 02/17/2021] [Indexed: 02/05/2023]
Abstract
The roles of Candida albicans CHK1, a key gene from two-component system, in oral mucosal infection are not clear. This study evaluated the key roles of CHK1 gene in vitro and in vivo. The expression of CHK1 and its regulated virulence factors were tested during the oral epithelial cell infection. The production of lactate dehydrogenase, ROS, and IL-1α combined with the confocal and scanning electron microscope observation was employed to identify the capability of CHK1 in damaging the epithelial cells. Both immunocompetent and immunodeficient mice oropharyngeal infection models were involved to confirm the roles of CHK1 gene in vivo. The expression of CHK1 gene was significantly increased during the oral epithelial cell infection. The chk1Δ/Δ mutant failed to damage the epithelial cells or induce IL-α and ROS production. Interestingly, chk1Δ/Δ can also form the similar hyphae with WT and complementary strains. Accordingly, chk1Δ/Δ did not affect the adhesion and invasion rates of C. albicans to oral epithelial cells. However, chk1Δ/Δ significantly decreased the expression levels of the virulence factors, including ALS2, SAP6, and YWP1. The chk1Δ/Δ also failed to cause oral candidiasis in both immunocompetent and immunodeficient mice indicating that CHK1 gene from the two-component system is essential for the pathogenicity of C. albicans. KEY POINTS: • CHK1gene is essential for C. albicans in oral candidiasis • C. albicans without CHK1 gene can form "non-pathogenic" hyphae. • CHK1 gene regulates the virulence of C. albicans.
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Affiliation(s)
- Yujie Zhou
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, Sichuan University, Chengdu, 610041, Sichuan, China
- Department of Operative Dentistry and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Lei Cheng
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, Sichuan University, Chengdu, 610041, Sichuan, China
- Department of Operative Dentistry and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Binyou Liao
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Yangyang Shi
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, Sichuan University, Chengdu, 610041, Sichuan, China
- Department of Operative Dentistry and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Yulong Niu
- Key Laboratory of Bio-resources and Eco-environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Chengguang Zhu
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, Sichuan University, Chengdu, 610041, Sichuan, China
- Department of Operative Dentistry and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Xingchen Ye
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, Sichuan University, Chengdu, 610041, Sichuan, China
- Department of Operative Dentistry and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Xuedong Zhou
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, Sichuan University, Chengdu, 610041, Sichuan, China.
- Department of Operative Dentistry and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, Sichuan, China.
| | - Biao Ren
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, Sichuan University, Chengdu, 610041, Sichuan, China.
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Pulmonary Mucormycosis: A Case Report of a Rare Infection with Potential Diagnostic Problems. Case Rep Pathol 2020; 2020:5845394. [PMID: 31970007 PMCID: PMC6973180 DOI: 10.1155/2020/5845394] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2019] [Accepted: 12/30/2019] [Indexed: 12/11/2022] Open
Abstract
Pulmonary mucormycosis is a relatively rare pulmonary fungal disease, which is difficult to diagnose early and lacks effective treatment. It is seen in patients with hematological malignancies, diabetes mellitus, and immunocompromised states. The diagnosis depends primarily on the detection of fungi in lung tissue. Here, we present a case of a 52-year-old male who has type 2 diabetes mellitus and a past history of treated pulmonary tuberculosis. Clinical diagnosis is difficult in pulmonary mucormycosis, and early diagnosis is needed for this life-threatening infection. Histopathological examination of a resected cavity confirmed the diagnosis of pulmonary mucormycosis. This report highlights the difficulty of diagnosis and the importance of histological examination in detecting mucormycosis which will help for early management.
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Thornton CR. Detection of the 'Big Five' mold killers of humans: Aspergillus, Fusarium, Lomentospora, Scedosporium and Mucormycetes. ADVANCES IN APPLIED MICROBIOLOGY 2019; 110:1-61. [PMID: 32386603 DOI: 10.1016/bs.aambs.2019.10.003] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Fungi are an important but frequently overlooked cause of morbidity and mortality in humans. Life-threatening fungal infections mainly occur in immunocompromised patients, and are typically caused by environmental opportunists that take advantage of a weakened immune system. The filamentous fungus Aspergillus fumigatus is the most important and well-documented mold pathogen of humans, causing a number of complex respiratory diseases, including invasive pulmonary aspergillosis, an often fatal disease in patients with acute leukemia or in immunosuppressed bone marrow or solid organ transplant recipients. However, non-Aspergillus molds are increasingly reported as agents of disseminated diseases, with Fusarium, Scedosporium, Lomentospora and mucormycete species now firmly established as pathogens of immunosuppressed and immunocompetent individuals. Despite well-documented risk factors for invasive fungal diseases, and increased awareness of the risk factors for life-threatening infections, the number of deaths attributable to molds is likely to be severely underestimated driven, to a large extent, by the lack of readily accessible, cheap, and accurate tests that allow detection and differentiation of infecting species. Early diagnosis is critical to patient survival but, unlike Aspergillus diseases, where a number of CE-marked or FDA-approved biomarker tests are now available for clinical diagnosis, similar tests for fusariosis, scedosporiosis and mucormycosis remain experimental, with detection reliant on insensitive and slow culture of pathogens from invasive bronchoalveolar lavage fluid, tissue biopsy, or from blood. This review examines the ecology, epidemiology, and contemporary methods of detection of these mold pathogens, and the obstacles to diagnostic test development and translation of novel biomarkers to the clinical setting.
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