Comparative risk assessment of COVID‐19 associated mucormycosis and aspergillosis: A systematic review
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COVID-19 is not only limited to a defined array but also has expanded with several secondary infections. Two uncommon opportunistic fungal infections, COVID-19 associated mucormycosis (CAM) and aspergillosis (CAA), have recently been highly acquainted by many worldwide cases. Two immune response deteriorating factors are considered to be responsible for immunosuppression: comorbidities and medication. Due to unlike infection sites and patterns, CAM and CAA-associated factors deflect a few degrees of proximity, and the present study is for its assessment. The study evaluated 351 CAM cases and 191 CAA cases retrieved from 65 and 53 articles based on inclusion criteria, respectively. Most of the CAM reported from India and CAA were from four South-European and West-European neighbor countries. The mean ages of CAM and CAA were 52.72 ± 13.74 and 64.81 ± 11.14, correspondingly. Mortality of CAA (56.28%) was two times greater than CAM (26.02%). Nevertheless, the count of diabetes cases was very high in CAM compared to CAA. The main comorbidities of CAM were diabetes (nearly 80%) and hypertension (more than 38%). All noticeable complications were higher in CAA except diabetes, and these were diabetes (34.55%), hypertension (45.03%), and obesity (18.32%). Moreover, pre-existing respiratory complications like asthma and chronic obstructive pulmonary disease are visible in CAA. The uses of steroids in CAM and CAA were nearly 70% and 66%, respectively. Almost one-fourth of CAA cases were reported using immunosuppressant monoclonal antibodies, whereas only 7.69% were for CAM. The overall finding highlights diabetes, hypertension, and steroids as the risk factors for CAM, whereas obesity, chronic pulmonary disease, and immunosuppressants for CAA.Keywords:
Immunosuppression
Abstract Background. Data on the accuracy of conventional histomorphologic diagnosis are limited, especially in mucormycosis. We therefore investigated the accuracy of histomorphologic diagnosis of mucormycosis and aspergillosis, using immunohistochemistry (IHC) tests for mucormycosis and aspergillosis. Methods. Patients enrolled met the modified criteria for proven and probable mucormycosis (during a 22-year period) or invasive aspergillosis (during a 6-year period) and had formalin-fixed, paraffin-embedded tissues available. We first tested the diagnostic performance of IHC for mucormycosis and aspergillosis in proven cases. Then we determined the accuracy of histomorphologic diagnosis of probable cases, using the IHC tests. Results. In 7 proven cases of mucormycosis, the sensitivity and specificity of mucormycosis IHC were 100% (95% confidence interval, 65%–100%) and 100% (68%–100%), respectively. In 8 proven cases of aspergillosis, and the sensitivity and specificity of aspergillosis IHC staining were 87% (53%–98%) and 100% (65%–100%), respectively. Of 23 probable mucormycosis cases, 20 (87%) were positive with mucormycosis IHC, 2 (9%) were positive with aspergillosis IHC (including 1 positive for both), and 2 were negative with both. Of 16 probable aspergillosis cases, 10 (63%) were positive with aspergillosis IHC, 4 (25%) were positive with mucormycosis IHC, and 2 (13%) were negative with both tests. Conclusions. Aspergillosis and mucormycosis seem not to be correctly diagnosed morphologically, because some of the probable cases showed either test with both antibodies or failure to stain with the homologous antibody. In the absence of fungal culture results, the IHC tests seem helpful in differentiating between aspergillosis and mucormycosis.
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Mucormycosis is caused by fungi of the order Mucorales and is one of the most rapidly fatal fungal infections known to man. Rhinocerebral mucormycosis is the most common type and its extension to the orbit and brain is quite usual. Location of mucormycosis on the palate is a rare and late occurrence. A case of deep hard palate ulcer due to sinonasal mucormycosis in a 79-year-old man is reported. He was successfully treated with a combination of surgical debridement and systemic liposomal amphotericin B administration for six weeks. By presenting this case report we would like to point out that mucormycosis should be included in the differential diagnosis of hard palate ulcers.
Hard palate
Mucorales
Zygomycosis
Surgical debridement
Debridement (dental)
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Mucormycosis is an angioinvasive infection caused by Zygomycosis in the order of Mucorales. It is mainly affected in immunocompromised individuals followed by risk factors such as diabetes mellitus, stem cell transplantation, organ transplantation, hematological malignancy, and more intake of steroids. Rhino-orbito-cerebral mucormycosis, pulmonary mucormycosis, cutaneous mucormycosis, gastrointestinal mucormycosis, and disseminated mucormycosis are the most common types. Moreover, it can be diagnosed to overcome this infection using the following methods such as histopathology cultures, computed axial tomography, and resonance imaging. Moreover, it can be treated with amphotericin B, the first-line drug, and posaconazole and isavuconazole are also used. The in vitro studies reveal the antifungal drugs which show the best activity against mucormycosis. The main aim of this review shows the detailed study of mucormycosis and the outcome of this infection.
Zygomycosis
Mucorales
Posaconazole
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Mucormycosis is a life-threatening fungal infection caused by mucormycetes, fungi of the Mucorales order.1 Rhino-orbital-cerebral involvement is the most common form of invasive mucormycosis. However, gastrointestinal (GI) mucormycosis cases have increased in the last two to three decades.2 Involvement of the GI tract in invasive mucormycosis is seen in 7–13% of cases.3 Out of which, involvement of the stomach is seen in 58% of the cases, and the remaining 42% involve small and large intestines. GI mucormycosis has been mostly associated with immunocompromised patients or premature infants.2 It has also been reported in immunocompetent patients.1 Many cases of GI mucormycosis are first recognized on autopsy, owing to its acute course and rapidly fatal nature.2 According to the literature, only about 25% of cases of GI mucormycosis are clinically diagnosed.4 The endoscopic appearance of gastric mucormycosis is usually a large ulcer with necrosis, eventually presenting an adherent, thick, green exudate.3 Figures 1A typically show green exudates surrounding the lesions. Autopsy diagnosis of GI mucormycosis is mostly based on gross and histopathological examination. Grossly, numerous well-circumscribed, dark red, targetoid mucosal lesions have been described in the post-mortem diagnosis of GI mucormycosis.4 Figures 1A show the so-called 'targetoid lesion' in the stomach mucosa. Figure 1 A - Macroscopic view of the stomach with multiple targetoid lesions of varying size, round to oval in shape with elevated margins and necrotic base (scale bar= 5 cm); B - Section from stomach depicting the transition zone between viable and necrotic tissue, left side of the image shows viable gastric tissue with patent submucosal blood vessels, while the right side shows bland necrosis with obliterated blood vessels (H&E, 20x); C and D - Gomori methenamine silver (GMS) and Periodic acid Schiff (PAS) stains highlight the angioinvasive fungal profiles within the submucosal blood vessels (400x). These hyphae are broad, aseptate foldable with right angle branching conforming to the morphology of mucormycosis.: Clinical diagnosis of GI mucormycosis is challenging. It can present an array of nonspecific symptoms, including discomfort, diarrhea, fever, gastrointestinal bleeding, necrosis, perforation, and as a necrotizing enterocolitis in premature neonates.5 The mechanism of GI tract involvement in mucormycosis is unclear. Pre-existing peptic ulcer disease, consumption of food and water contaminated with Mucorales, and use of contaminated nasogastric tubes, tongue depressors, and wooden spatula are a few factors responsible for the involvement of the GI system in mucormycosis.5,6 Mortality rate of GI mucormycosis is reported as 40 to 78%.4,5 Perforation of necrotic ulcers and peritonitis are the leading causes of death in such cases. The reported images belong to a 48-year-old man who died from septicemia seven days after a road traffic accident. At autopsy, apart from findings of traumatic injuries, the stomach showed multiple rounds to oval lesions with sizes ranging from 0.5cm X 0.5 cm to 3cm X 2 cm, over the pylorus with elevated margins and necrotic base (Figure 1A). On the formalin-fixed specimen, they were noted as ulcers with a greenish-black base and flattened edges. The periphery of the ulcer was congested. The microscopic examination showed that the ulcers were extending to the muscularis propria. They were invading underlying arteries and veins in the submucosa, indicating angioinvasion (Figure 1B). Gomori methenamine silver (GMS) and Periodic acid Schiff (PAS) stains highlighted fungal hyphae, which were broad aseptate and foldable, confirming the morphology of mucormycosis (Figure 11D, respectively). In conclusion, gastric mucormycosis cases usually go unnoticed clinically unless it becomes symptomatic or diagnosed incidentally on endoscopy. Thus, such cases are being diagnosed at autopsy.
Mucorales
Zygomycosis
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In the past decade, mucormycosis has emerged as an important lethal infection in diabetics and other immunocompromised hosts. Rhinosinusitis, pansinusitis, rhino-orbital and rhinocerebral are the common classical manifestations of mucormycosis. However, primary gastrointestinal (GI) mucormycosis is an uncommon disease associated with a high mortality rate. Stomach is the most common site involved in GI mucormycosis. Reported cases of GI mucormycosis in an immunocompetent host are very few in the literature. Here we present a case of a young male with fungal sepsis secondary to GI mucormycosis in an immunocompetent person.
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To summarize the clinical features of patients with mucormycosis.We retrospectively analyzed the clinical data of all 9 cases of mucormycosis in our hospital from 1986 to 2009.The average age was(31 ∓ 19)years. The intervals between the onset of disease to diagnosis ranged from 1 weeks to 31 months. One patient had rhinocerebral mucormycosis, 4 had pulmonary mucormycosis, 2 had disseminated mucormycosis, and 1 had isolated central nervous system mucormycosis. Risk factors included long-term high-dose usage of corticosteroids, diabetes,acidosis, and extensive skin lesions. Laboratory analysis showed elevated erythrocyte sedimentation rate and increased C-reactive protein. Laboratory evidences also suggested 6 patients were obviously immunocompromised. Chest CT scans of all patients with pulmonary mucormycosis revealed bilateral multiple patches. All patients were treated with intravenous amphotericin B, and two patients also underwent surgeries. One of two patients with disseminated mucormycosis died, the patient with rhinocerebral mucormycosis was stabilized,and the other patients were improved.Mucormycosis is a rare disease, and all patients are immunocompromised. Due to the rapid progression and poor prognosis, early diagnosis and correct treatment are necessary and may improve survival.
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Summary Objective To investigate the accuracy of immunohistochemistry (IHC) tests for distinguishing between mucormycosis and aspergillosis and compare the clinical characteristics of mucormycosis patients according to galactomannan (GM) results. Methods We evaluated diagnostic performance of IHC test with tissue sections of patients with culture‐proven invasive fungal infection. In addition, we conducted PCR assay with tissue sections of mucormycosis patients with positive GM results to evaluate the possibility of co‐infection. Results In culture‐proven mucormycosis (n = 13) and aspergillosis (n = 20), the sensitivity and specificity of IHC test were both 100% for mucormycosis and 85% and 100%, respectively, for aspergillosis. Among the 53 patients who met the modified criteria for proven mucormycosis and had GM assay results, 24 (45%) were positive. Compared with those with negative GM results (n = 29), mucormycosis patients with positive GM results had significantly higher incidence of gastrointestinal tract infections (6/24 [25%] vs 0/29 [0%], P = .006) and were more likely to be histomorphologically diagnosed as aspergillosis (7/24 [29%] vs 2/29 [7%], P = .06). PCR assay amplified both Aspergillus ‐ and Mucorales ‐specific DNA in 6 of these 24 cases. Conclusions Immunohistochemistry tests seem useful for compensating for the limitations of histomorphologic diagnosis in distinguishing between mucormycosis and aspergillosis. Some proven mucormycosis patients with positive GM results had histopathology consistent with aspergillosis and gastrointestinal mucormycosis. In addition, about one quarter of these patients revealed the evidence of co‐infection with aspergillosis by PCR assay.
Mucorales
Galactomannan
Histopathology
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Mucormycosis is an opportunistic infection caused by the fungi of the Mucorales order of the class Zygomycetes. Gastrointestinal mucormycosis is an uncommon, fatal condition accounting for only 7% of the cases. We present the case of a gastroduodenal mucormycosis presenting as recurrent massive hematemesis. We report this case to alert clinicians of this rare but fatal condition and to encourage further research into its pathogenesis and management.
Mucorales
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Summary Mucormycosis remains a devastating invasive fungal infection, with high mortality rates even after active management. The disease is being reported at an alarming frequency over the past decades from India. Indian mucormycosis has certain unique features. Rhino‐orbito‐cerebral presentation associated with uncontrolled diabetes is the predominant characteristic. Isolated renal mucormycosis has emerged as a new clinical entity. Apophysomyces elegans and Rhizopus homothallicus are emerging species in this region and uncommon agents such as Mucor irregularis and Thamnostylum lucknowense are also being reported. This review focuses on these distinct features of mucormycosis observed in India.
Presentation (obstetrics)
Zygomycosis
Rhizopus
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Mucormycosis (MCR) is caused by filamentous molds within the Class Zygomycetes and Order Mucorales. Infections can result from inhalation of spores into the nares, oropharynx, or lungs, ingestion of contaminated food or water, or inoculation into disrupted skin or wounds. In developed countries, MCR occurs primarily in severely immunocompromised hosts. In contrast, in developing/low income countries, most cases of MCR occur in persons with poorly controlled diabetes mellitus and some cases in immunocompetent subjects following trauma. Mucormycosis exhibits a propensity to invade blood vessels, leading to thrombosis and infarction of tissue. Mortality rates associated with invasive MCR are high and can exceed 90% with disseminated disease. Mucormycosis can be classified as one of six forms: (1) rhino-orbital-cerebral mucormycosis (ROCM); (2) pulmonary; (3) cutaneous; (4) gastrointestinal or renal (5); disseminated; or (6) uncommon (focal) sites.The authors discuss the prevalence, risk factors, and clinical features of mucormycosis. A literature search of mucormycosis was performed via PubMed (up to November 2022), using the key words: invasivefungal infections; mold; mucormycosis;Mucorales; Zyzomyces; Zygomycosis; Rhizopus, diagnosis.Mucormycosis occurs primarily in severely immunocompromised hosts. Mucormycosis can progress rapidly, and delay in initiating treatment by even a few days worsens outcomes.
Mucorales
Zygomycosis
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