The ECMM/ISHAM Working Group on Zygomycosis
Table of Contents
Although often described as a rare fungal infection, mucormycosis appears to be increasing in frequency . This has been attributed to the growth of the number of severely immunocompromised patients, as well as to the rising prevalence of diabetes mellitus [1-3]. Differences in the epidemiology seem to exist depending on geography. In Europe and USA, the disease remains uncommon and is mostly seen in patients with hematological malignancies. In contrast, in Asia, especially in India, mucormycosis is more common, and cases occur mainly in patients with uncontrolled diabetes mellitus or trauma . It mainly affects immunocompromised patients, such as those with haematological malignancies, recipients of haematopoietic stem cell or solid organ transplants, patients with diabetes mellitus, and infants with prematurity . Mucormycosis may also affect immunocompetent patients with trauma or burns, or patients with elevated serum levels of iron under treatment with deferroxamine. Due to the relative rarity of the disease it is difficult to perform stringent epidemiological studies to estimate its exact incidence. Most of the available data stem from case series and pertain to haematological patients [5,6] or to patients who have undergone transplantation [7,8]. Taking into consideration the challenges related to epidemiology, treatment and outcome of mucormycosis, a Working Group on Zygomycosis was formed by the European Confederation of Medical Mycology (ECMM). The aim of the group was to analyze the clinical characteristics, microbiology, treatment practices and outcome of mucormycosis in Europe through a voluntary case registry. The results of the first 3 years (2005–2007) were published in 2011 . In 2008 the Working Group became global, under the auspices of both ECMM and ISHAM (Ιnternational Society for Human and Animal Mycology).
The aim of this registry is to collect as many cases of mucormycosis as possible from all around the world, in order to better understand the various aspects of this rare disease.
Further aims of the group are:
1. To collect strains of mucormycetes for state-of-the-art molecular identification and long-term maintenance. Strains will thus have official accession-numbers which can be used in future publications.
2. To collect any available histology specimen for PCR. This will aid in the identification of fungi when no cultures are available, as well as for comparison with culture proven strains.
Start of study: February 1, 2004.
First amendment of study: January 1, 2008.
End of study: not defined yet.
The data pertaining to the case can be submitted either on-line or on a CRF form. The address of the on-line registry is www.zygomyco.net . The CRF form will be downloaded from the registry site and sent by e-mail to the study coordinators when completed.
In order to submit a case, a participant must register to the site, giving his name, country of origin and e-mail address.
All the parts of the form should be completed. The requested information includes:
Initials: These are random letters or numbers chosen by the submitting participant.
Country – City: This is the country of residence of the patient, not of the submitting participant.
Patient code: This is an automatic number, provided by the registry
Age: (Years: Months: ) Months are completed if the patient is an infant.
Sex: Female or Male
Name of Physician: This is either the name of the clinician treating the patient or of the mycologist making the laboratory diagnosis.
Date Zero: This is the date when the diagnosis of mucormycosis was made or, alternatively, where the clinical signs and symptoms were attributed to mucormycosis.
Underlying Disease at time of infection: Enter yes or no. If yes, indicate which of the following are positive
Treatment BEFORE diagnosis of zygomycosis:
These are the drugs given before the diagnosis of mucormycosis. If any antifungals were used, please insert the reason for using them. For example, this could be “empirical treatment for presumed aspergillosis” or “prophylaxis in transplantation” etc.
Mode of transmission
If the mode of transmission was not identified, don’t forget to insert “Yes” next to “Unknown”.
Site of infection
An infection is characterized as “localized” if it does not extend to adjacent organs. For example, if the site of infection is pulmonary and the infection extends to the pleura or the pericardium, then it is not localized.
If more than one organ is infected, and the organs are non-contiguous (e.g. lung and kidney) than the infection is “disseminated”. In this case, only the site “disseminated” should be chosen and the involved organs should be mentioned next to it.
Signs and symptoms of fungal infection
Please insert a paragraph describing the clinical presentation of the infection.
The methods of diagnosis MUST be completed, otherwise the case will not be included in the study. The results of the studies must be reported.
Treatment of Zygomycosis
Insert all available information. If the patient has received a polyene (conventional or liposomal amphotericin B) the dose should be written as mg/kg of body weight.
If the participant wishes, he can send the isolated fungus to the laboratory of Dr. Cuenca-Estrella in Spain for molecular identification and susceptibility testing.
If an histology specimen is available, it can be sent to the same lab for PCR testing.
For every case submitted €100 will be given as compensation.
The cost for the tests done by Dr. Cuenca-Estrella and Dr. Ana-Alastruey Izquierdo will be covered by the Working Group budget.
The study is non-interventional and, therefore, no informed consent is required according to the laws of most countries. There are no associated risks or benefits for the patient when participating in the study. The digital documentation of the clinical data will take place in an anonymized fashion. No identifiable data, e.g. name or date of birth will be entered into the database. Clinical data collected refers to common conditions and treatment modalities in medical care, such that no re-identification of the individual case on the basis of these data will be possible. The data submitted to the site are protected from unauthorized access and loss. Contributors can only view the cases submitted by themselves. All study procedures are liable to Good Epidemiological Practice (GEP) requirements according to European legislation. All data and results will be stored for at least 10 years after publication of results.
To ensure anonymity of all patients in the context of microbiological reference analyses, these analyses must have been completed and the results must have been included into the respective patient file, before the entire case is documented into the database. This procedure aims to ensure anonymous documentation of patient data. The microbiological analyses of isolates does not require informed consent of the patient, as there is no patient material involved.
Acting Dean, School of Medicine
Professor of Immunology, Medical Microbiology and Infectious Diseases
Tel: 00357 22559532, mob: +357 99663060
Emeritus Professor of Internal Medicine and Infectious Diseases
National and Kapodistrian University of Athens
1st Dpt. of Medicine, Laikon Hospital
Agiou Thoma 18, Goudi 11527, Athens, Greece
National and Kapodistrian University of Athens
Tel: +30 6944354279
Subdirector General de Servicios Aplicados, Formación e Investigación
Instituto de Salud Carlos III
(Deputy General Director of Institute of Health Carlos III)
Ctra. Majadahonda-Pozuelo Km2
Majadahonda, Madrid 28220
Tfno/phone: +34 91 8223200
Mycology Reference Lab
National Centre for Microbiology
Instituto de Salud Carlos III
Carretera de Majadahonda a Pozuelo Km. 2
28220, Majadahonda, Madrid, Spain
Zygomyco.net Study Protocol, version 3, 20 June, 2017