A prospective multicenter study on mucormycosis in India: Epidemiology, diagnosis, and treatment

Prakash, Hariprasath; Ghosh, Anup; Rudramurthy, Shivaprakash M.; Singh, Pankaj; Xess, Immaculata; Savio, Jayanthi; Umabala, P; Jillwin, Joseph; Varma, Subhash; Das, Ashim; Panda, Naresh K.; Singh, Surjit; Bal, Amanjit; Chakrabarti, Arunaloke

doi:10.1093/mmy/myy060

Cited by 276 publications

(306 citation statements)

References 37 publications

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“…Risk factors for mucormycosis vary considerably by geographical area. In studies from Europe [10,14,27] the most common underlying disease was a hematological malignancy, while in India [5,11,20,29], Iran [29,31] and Mexico [12] it was diabetes mellitus. Diabetes was also the leading underlying condition in the study by Stemler et al in countries of the Middle East and North Africa [34].…”

Section: Predisposing Factors/underlying Conditionsmentioning

confidence: 99%

Epidemiology and Diagnosis of Mucormycosis: An Update

Skiada

Pavleas

Drogari‐Apiranthitou

2020

JoF

440

444

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Mucormycosis is an angioinvasive fungal infection, due to fungi of the order Mucorales. Its incidence cannot be measured exactly, since there are few population-based studies, but multiple studies have shown that it is increasing. The prevalence of mucormycosis in India is about 80 times the prevalence in developed countries, being approximately 0.14 cases per 1000 population. Diabetes mellitus is the main underlying disease globally, especially in low and middle-income countries. In developed countries the most common underlying diseases are hematological malignancies and transplantation. Τhe epidemiology of mucormycosis is evolving as new immunomodulating agents are used in the treatment of cancer and autoimmune diseases, and as the modern diagnostic tools lead to the identification of previously uncommon genera/species such as Apophysomyces or Saksenaea complex. In addition, new risk factors are reported from Asia, including post-pulmonary tuberculosis and chronic kidney disease. New emerging species include Rhizopus homothallicus, Thamnostylum lucknowense, Mucor irregularis and Saksenaea erythrospora. Diagnosis of mucormycosis remains challenging. Clinical approach to diagnosis has a low sensitivity and specificity, it helps however in raising suspicion and prompting the initiation of laboratory testing. Histopathology, direct examination and culture remain essential tools, although the molecular methods are improving. The internal transcribed spacer (ITS) region is the most widely sequenced DNA region for fungi and it is recommended as a first-line method for species identification of Mucorales. New molecular platforms are being investigated and new fungal genetic targets are being explored. Molecular-based methods have gained acceptance for confirmation of the infection when applied on tissues. Methods on the detection of Mucorales DNA in blood have shown promising results for earlier and rapid diagnosis and could be used as screening tests in high-risk patients, but have to be validated in clinical studies. More, much needed, rapid methods that do not require invasive procedures, such as serology-based point-of-care, or metabolomics-based breath tests, are being developed and hopefully will be evaluated in the near future.

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Section: Predisposing Factors/underlying Conditionsmentioning

confidence: 99%

Epidemiology and Diagnosis of Mucormycosis: An Update

Skiada

Pavleas

Drogari‐Apiranthitou

2020

JoF

440

444

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“…Several conditions have been associated with the development of mucormycosis (►Table 1), including: poorly controlled DM 1,15,20,[62][63][64][65][66][67] ; HemeM with neutropenia 61,65,[68][69][70][71][72] ; HSCT 48,[73][74][75][76][77] ; SOTRs 19,52,63,75,[78][79][80][81][82] ; immunosuppression or chemotherapy 23,59,83 ; autoimmune or rheumatic disorders 59,84 ; human immunodeficiency virus infection 14,[85][86][87][88] ; peritoneal dialysis [89][90][91][92] ; iron overload states 37,38,93 ; malnutrition 23 ; trauma 67 ; burns…”

Section: Risk Factors For Mucormycosismentioning

confidence: 99%

“…7,[95][96][97][98] A recent meta-analysis of 600 publications from 2000 to 2017 comprising 851 cases of mucormycosis worldwide cited the following risk factors: DM (40%); trauma (33%); HemeM (32%); diabetic ketoacidosis (20%); neutropenia (20%); no underlying disease (18%); SOTR (14%); burns (11%); and natural disasters (5%). 20 In Asia, DM is the most common risk factor for mucormycosis, 20,67,99 whereas organ transplants and HemeM are more common in Europe and North America. 20…”

Section: Risk Factors For Mucormycosismentioning

confidence: 99%

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Mucormycosis

Reid

Lynch

Fishbein

et al. 2020

Semin Respir Crit Care Med

132

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Mucormycosis is an infection caused by a group of filamentous molds within the order Mucorales. Infections may result from ingestion of contaminated food, inhalation of spores into the nares or lungs, or inoculation into disrupted skin or wounds. In developed countries, mucormycosis occurs primarily in severely immunocompromised hosts (e.g., those with hematological malignancies, organ transplantation, neutropenia, autoimmune disorders, or other impairments in immunity). Only 6 to 10% of cases occur in subjects with no underlying disease. In contrast, in developing countries, most cases of mucormycosis occur in persons with poorly controlled diabetes mellitus or in immunocompetent subjects following trauma. Mucormycosis exhibits a marked propensity to invade blood vessels, leading to thrombosis, necrosis, and infarction of tissue. Mortality associated with invasive mucormycosis is high (> 30–50%), with 90% mortality associated with disseminated disease. Mortality rates are much lower, though still significant (10–30%), among patients with localized cutaneous disease.The diagnosis of mucormycosis relies upon histopathology and culture. Blood tests are of limited diagnostic value. Even with disseminated disease, blood cultures are usually negative. Mucorales have a distinct histological appearance, with irregular, nonseptate hyphae that branch at right angles. Cultures and/or polymerase chain reaction (PCR) are important to identify the genera.Based on anatomic localization, mucormycosis can be classified as one of six forms: (1) rhino-orbital-cerebral mucormycosis (ROCM), (2) pulmonary, (3) cutaneous, (4) gastrointestinal (GI), (5) disseminated, and (6) mucormycosis of uncommon sites. Among diabetics, ROCM is the most common clinical presentation, whereas lung involvement is uncommon. In contrast, among organ transplant recipients or patients with hematological malignancies (HemeM), pulmonary and disseminated diseases are most common. Mucormycosis can progress rapidly, and delay in initiation of treatment by even a few days markedly worsens outcomes.Due to the rarity of mucormycosis, randomized controlled therapeutic trials have not been performed. Lipid formulations of amphotericin B (LFAB) are the mainstay of therapy, but the newer triazoles, posaconazole (POSA) and isavuconazole (ISAV) (the active component of the prodrug isavuconazonium sulfate), may be effective in patients refractory to or intolerant of LFAB. Early surgical debridement or excision plays an important adjunctive role. Additional studies are required to assess the optimal duration of therapy as well as the specific roles of LFAB and the triazoles in the treatment of mucormycosis.

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“…As such, the ECMM has recently begun a “neglected orphan disease guidance initiative” focusing on this disease both within and beyond the European region . Several previous studies have gathered data on mucormycosis in patients in Europe, Asia or other areas, but to date, there has been no comprehensive review of the literature on mucormycosis in South America. Here, we collate and review mucormycosis case studies reported in South American countries, exploring patient characteristics, course of infection, treatment regimens and clinical outcomes.…”

Section: Introductionmentioning

confidence: 99%

Mucormycosis in South America: A review of 143 reported cases

Nucci

Engelhardt

Hamed

2019

Mycoses

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SummaryMucormycosis is a rare but important invasive fungal disease that most often affects immunocompromised hosts. The incidence of mucormycosis appears to be increasing worldwide, as risk factors such as the use of immunosuppressive therapies become more common. We report the results of a literature review of 143 mucormycosis cases reported in South America between 1960 and 2018. The number of reported cases has increased by decade, from 6 in the 1960s to 51 in the 2010s. The most common underlying conditions associated with mucormycosis in South America were diabetes mellitus (42.0%) and penetrating trauma/burns (20.0%). Underlying conditions involving immunosuppression, including treatment of haematologic malignancy, solid organ transplant, and corticosteroid use, also accounted for a large proportion of cases (45.5%). Between 1960 and 2018, cases of mucormycosis associated with conditions involving immunosuppression accounted for the highest mortality rate (58.5%), followed by diabetes mellitus (45.0%), and penetrating trauma/burns (37.9%). Overall mortality decreased from 100% to 39.4% during this period, mainly driven by the increasing availability and use of antifungal therapies and surgical intervention. However, these treatments are not yet universally utilised across the region in the treatment of mucormycosis; efforts to improve availability of effective treatments would be likely to improve outcomes.

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A prospective multicenter study on mucormycosis in India: Epidemiology, diagnosis, and treatment

Cited by 276 publications

References 37 publications

Epidemiology and Diagnosis of Mucormycosis: An Update

Epidemiology and Diagnosis of Mucormycosis: An Update

Mucormycosis

Mucormycosis in South America: A review of 143 reported cases

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