Mycology The ECMM/CEMM Mycology Newsletter is mailed ... · of medical mycology in Portugal. During...

Message from the President

The ECMM President is happy to take the opportunity of thisfirst issue of the ECMM Newsletter to greet all ECMM

members and their Mycological Societies and extend a cordialwelcome to the Russian Society of Mycology which has recentlyjoined our Confederation.

We had an excellent Congress inLisboa and we do hope that such ameeting will boost the developmentof medical mycology in Portugal.During this meeting Dr. MariaAnna Viviani was elected by theCouncil to the position of GeneralSecretary. I would like to expressmy warmest thanks to Dr. DavidWarnock, who had the difficult taskof being the first General Secretary,for his considerable effort in settingup the Confederation from nothing.

We realized during the lastCouncil meeting in Lisboa thatcommunication was sometimes dif-ficult or slow between delegatesand their Societies and between the19 Mycological Societies or Groups. For this reason we decided topublish a Newsletter with two issues per year mailed to all indi-vidual ECMM members. The General Secretary is in charge ofediting the Newsletter. This method of communication is very im-portant and I encourage everyone to participate in the venture bysending their comments or suggestions to Dr. Viviani. One of thepurposes of the Newsletter is to activate the Working Groupswhich are a major goal of our Confederation. If you are interestedin participating in these Working Groups please contact your na-tional delegate.

We would like to have the first reports of these groups duringa special Session at the next ECMM Congress which will be heldin Glasgow on 11-13 May 1998 with Gillian Shankland as organiz-er. I thank warmly all delegates, Maria Anna Viviani and LarsEdebo, our Treasurer, for their efforts and their commitment toECMM.

Bertrand Dupont

Contents

1 Message from the President

2 ECMM Council

3 Affiliated Societies

3 The Third Meeting of the ECMM

3 A joint ISHAM-ECMM session at the 13th Congress of the ISHAM

Epidemiological Working Groups of ECMM

4 Introduction

5 Rules for EpidemiologicalWorking Groups

6 Survey of cryptococcosis in Europe

8 Survey of histoplasmosis in Europe

10 Survey of nocardiosis in Europe

12 Survey of candidemia in Europe

15 Survey of tinea capitis in Europe

Special report on 3rd International Conference On Cryptococcus and Cryptococcosis

16 Introduction

17 Molecular biology and biochemistry

18 Taxonomy, epidemiology, and ecology

19 Immune responses in cryptococcosis

20 Pathogenesis and host responses

21 Drugs and therapy for cryptococcosis

22 Clinical manifestations and diagnosis

23 Cryptococcal polysaccharide

24 Mycology Courses in Europe (1997)

Mycologynewsletter 0/97

E C M MEuropean Confederation of Medical Mycology

C E M MConfédération Européenne de Mycology Médicale

The ECMM/CEMM Mycology Newsletter is mailedto the members of the national societies affiliatedto the European Confederation of MedicalMycology (about 3000 in 19 different countries)

ECMM CouncilProf. Bertrand Dupont (President)Unité de Mycologie, Institut Pasteur25 rue du Docteur RouxF-75724 Paris, Cedex 15, FranceTel: +33 1 4568 8354 Fax: +33 1 4568 8420

Prof. Maria Anna Viviani (General Secretary)Ist. di Igiene e Medicina PreventivaUniversità degli Studi di Milanovia Francesco Sforza 35I-20122 Milano, ItalyTel: +39 2 5518 8373 / 55033487Fax: +39 2 5519 1561E-mail: [email protected]

Prof. Lars Edebo (Treasurer)Dept of Clinical BacteriologyUniversity of GöteborgGuldhedsgatan 10S-41346 Göteborg, SwedenTel: +46 31 604914 - Fax: +46 31 604975

Prof. Eugeniusz Baranul Chalubinskiego 1PL-50-368 Wroclaw, PolandTel: +48 71 209864 - Fax: +48 71 215729

Dr. Israela BerdicevskyDept. of MicrobiologyTechnion, Faculty of MedicineP.O. Box 9649Haifa 31096, IsraelTel: +972 4 829 5293Fax: +972 4 829 5225

Prof. Hannelore BernhardtUniversität Greifswald Klinik für Innere MedizinAbt. für Klin. MikrobiologieFriedrich-Loeffler-Straße 23aD-17489 Greifswald, GermanyTel: +49 3834 866630Fax: +49 3834 866602

Dr. Sofia A. BurovaMoscow Center of Deep Mycoses10, Lobnenskaya Str.Moscow 127644RussiaTel: +7 95 483 5683 Fax: +7 95 483 0247/5066

Prof. E. Glyn V. EvansPHLS Mycology Ref. Lab.Dept. of MicrobiologyUniversity of LeedsUK-Leeds LS2 9JT, United KingdomTel: +44 113 233 5600 Fax: +44 113 233 5587E-mail: [email protected]

Dr. G. Sybren de HoogCentraalbureau voor SchimmelculturesP.O. Box 273NL-3740 AG Baarn, The NetherlandsTel: +31 3554 81253Fax: +31 3554 16142E-mail: [email protected].

Prof. Todor KantardjievNational Center for Infectious DiseasesLaboratory of MycologyBvld. Yanko Sakazov 2BG-1504 Sofia, BulgariaTel: +359 2 465520 - Fax/Tel: +359 2 655878

Prof. O. Marcelou-KintiDept. of ParasitologyAthens School of Public Health196 Alexandras Avenue11521 Athens, GreeceTel: +30 1 6462045 - Fax: +30 1 6444260

Dr. Michel MonodDépartement de DermatologieHôpital UniversitaireCH-1011 Lausanne, SwitzerlandTel: +41 21 3142823 - Fax: +41 21 3142825

Prof. Jose PontonDepartamento de MicrobiologiaFacultad de Medicina y OdontologíaApartado 699E-48080 Bilbao, Vizcaya, SpainTel: +34 4 4647700 Ext 2745Fax: +34 4 4648152E-mail: [email protected]

Dr. Laura RosadoInstitute of HealthAv. Padre CruzP-1699 Lisboa Codex, PortugalTel: +351 1 7577070 -Fax: +351 1 7590441

Dr. Jørgen StenderupLaboratory for MycologyDept. of BacteriologyStatens SeruminstitutArtillerivej 5DK-2300 Copenhagen S, DenmarkTel: +45 3268 3531 - Fax: +45 3268 3868

Prof. Danielle SwinneLaboratory for MycologyInst. of Tropical MedicineNationalestraat 155B-2000 Antwerp 1, BelgiumTel: +32 3 2476666 - Fax: +32 3 2161431

Prof. Alena TomsíkováInst. of Microbiology LFDr E. Benes Street 13305 99 Plzen, Czech RepublicTel: +42 19 221200 Fax: +42 19 221460

Prof. Ibolya TörökSemmelweis University of MedicineDept. of Dermato-VenereologyMária u. 41, BudapestH-1085 HungaryTel: +36 1 210 0310 - Fax: +36 1 210 4874

Prof. Emel TumbayDept. of MicrobiologyEge University School of MedicineBornova, Izmir, TurkeyFax: +90 51 882 852

Mycology newsletter - March19972

ECMM/CEMMMycology newsletter

Editorial Advisory BoardFrançoise DromerE. Glyn V. EvansMaria Anna Viviani (Editor)

Direttore responsabileIvan Dragoni

Art Director Luigi Naro

Contributions from:Patrick Boiron, Françoise Dromer,Bertrand Dupont, David H. Ellis,E. Glyn V. Evans, John R. Graybill,Renée Grillot, Roderick J. Hay,Thomas R. Kozel, K. June Kwon-Chung,Juneann W. Murphy, Gillian S.Shankland, Maria Anna Viviani

Printed by:Lasergrafica Polvervia Kramer, 17/19Milano, Italy

© Copyright 1997 by EuropeanConfederation of Medical MycologyOfficial Office: c/o Institut Pasteur,28 rue du Dr. Roux, 75015 Paris, France

Published with a grant fromThe Liposome Company Ltd.Tel: +44 181 3240058Fax: +44 181 5631653

Mycology newsletter - March1997 3

Affiliated SocietiesAssociação Portuguesa de MicologiaMédica (ASPOMM)President: M. RochaVicepresident: R.M. VelhoSecretary: M.L. Rosado (ECMM delegate)Treasurer: M. GardeteMembership 1996: 47National meeting: May 1997, LisboaNewsletter

Asociacion Española de MicologiaSeccion de Micologia MedicaPresident: J.M. Torres RodriguezVicepresident: M.L. Abarca SalatSecretary: S. Santamaria del CampoTreasurer: A.J. Carrillo MuñozPresident Mycology Section: J. Ponton(ECMM delegate)Membership 1996: 65National meeting: 1998, CadizJournal: Revista Iberoamericana deMicologia

British Society for Medical Mycology(BSMM)President: E.G.V. Evans (ECMM delegate)Secretary: D.W. WarnockTreasurer: G.S. ShanklandMembership 1996: 260 National meeting: 11-13 May, 1998,Glasgow (joint with ECMM Congress)Newsletter

Bulgarian Mycological Society (BMS)President: T. Kantardjiev (ECMM delegate)Membership 1996: 27

Czech Mycological GroupECMM delegate: A. Tomsíková

Danish Society for MycopathologiaPresident: E. SvejgaardSecretary: M. KiefferTreasurer: J. Stenderup (ECMM delegate)Membership 1996: 65

Deutschsprachige MykologischeGesellschaft e.V. (DMykG)President: H.Bernhardt (ECMM delegate)Vicepresident: H. Chr. KortingSecretary: C. SeebacherTreasurer: W. FegelerMembership 1996: 1100National meeting: September 18-21, 1997,Aachen

Federazione Italiana di MicopatologiaUmana e Animale (FIMUA)President: M.A. Viviani (ECMM delegate)Vicepresident: S. OliveriSecretary: I.G. DragoniTreasurer: G. MoraceMembership 1996: 150National meeting: Autumn 1998, MilanoNewsletter

Greek Mycological GroupECMM delegate: O. Marcelou-Kinti

Hungarian Dermatological SocietyMycology SectionPresident: I. Török (ECMM delegate)Secretary: G. FeketeMembership 1996: 25 National meeting: March 21, 1997,Budapest

Israel Society for Medical MycologyPresident: E. SegalSecretary: I. Berdicevsky (ECMM delegate)Treasurer: D. EladMembership 1996: 80

Polish Dermatologic SocietyMycology SectionPresident: E. Baran (ECMM delegate)Vicepresident: P. RatkaSecretary-Treasurer: M. ZiarkiewiczMembership 1996: 98National meeting: September 25-27, 1997,Zakopane-KoscieliskoJournal: Mykologia Lekarska (MedicalMycology)

Netherland Society for Human andVeterinary Mycology (NVMy)President: R.G.F. WintermansScientific Secretary: G.S. de Hoog (ECMMdelegate)Secretary: E.P.F. YzermanTreasurer: R.W. BrimicombeMembership 1996: 110 National meeting: April 2, 1997, Lunteren

Russian Society of MycologyPresident: S.A. Burova (ECMM delegate)Vicepresident: V.B. AntonovSecretary: N.M. VasilyevaTreasurer: I.V. KurbatovaMembership 1996: 25

Société Belge de Mycologie Humaine etAnimale / Belgische Vereniging VoorMenselijke en Dierlijke MycologiePresident: N. NolardVicepresident: H. Vanden Bossche, M. SongSecretary: D. Robbrecht, J. BoelaertTreasurer: M.C. LestienneECMM Delegate: D. SwinneMembership 1996: 210National meeting: April 19, 1997, Antwerp

Société Française de Mycologie MédicalePresident: J.P. SeguelaVicepresident: R. Grillot, C. de BievreSecretary: B. Dupont (ECMM delegate) Treasurer: P. BoironMembership 1996: 360National meeting: March 20-21, 1997,Arcachon - November 27-28, 1997, ParisJournal: Journal de Mycologie Médicale

Swedish Society for Clinical MycologyPresident: J. FaergemannVicepresident: T. KaamanSecretary: G. PålssonTreasurer: L. Edebo (ECMM delegate) Membership 1996: 97National meeting: Autumn 1997, GöteborgNewsletter

Swiss Mycological GroupECMM delegate: M. Monod

Turkish Microbiological SocietyMycology SectionPresident: Ö. AngECMM delegate: E. TümbayMembership 1996: 21

The Third Meeting of theECMM 9-11th May 1996

The 1996 meeting of the Confedera-tion was hosted by the PortugueseSociety in the interesting city of Lisboa.The 260 delegates converged on the AlfaHotel near the center of the city to hearthe verbal communications and read the100 plus posters scientific sessions startedwith the History of Medical Mycology inBrazil. There were round table sessionson systemic mycoses in immunocompro-mised host, public health mycology anddermatological mycology, these werethought provoking and excited some de-bate. Other invited speakers fromEurope, USA and Brazil covered a widerange of topics including taxonomy,pathogenesis, clinical mycology, epidemi-ology and molecular mycology. New ther-apies for mycoses were presented and thesusceptibility testing for antifungal drugswas discussed.There was also a session onveterinary aspects of mycology.

There was a programme ofPortuguese entertainment most eveningsand tours of the city were available. Aboat trip on the river Tagus at sunsetrounded off the social events.

The Lisboa meeting will long be re-membered for its organisation and theexcellent chance it afforded the partici-pants to reacquaint themselves with oldfriends, make new friends and exchangeideas.

The fourth meeting of the EuropeanConfederation of Medical Mycology willtake place in Glasgow, 11th-13th May1998. I look forward to welcoming TheECMM to Scotland.

Gillian S. Shankland

A joint ISHAM-ECMM session At the 13th Congress of the

International Society for Human andAnimal Mycology (ISHAM), which willbe held in Parma, Italy, 8-13 June, 1997, asession organized jointly by ISHAM andECMM will be dedicated to “Importedmycoses in Europe”.

The symposium, chaired by Prof.Bertrand Dupont and Dr. DavidWarnock, will include reports by:• B. Dupont (France): Histoplasmosis inFrance 1970-1995• T. Sirisanthana (Thailand): Diagnosisand management of Penicillium marnef-fei infection• C. Kauffman (USA): New develop-ments in the diagnosis of endemic my-coses• D. Warnock (UK): Imported mycoses:risks for European laboratory workers.

There is much work to be done in thisarea as epidemiological knowledge

is still too scanty, being limited to somecountries with national societies inter-ested in the topic. In fact, a map of thefrequency and distribution of fungal in-fections in Europe is still lacking, and itis necessary to clarify their aetiology,pathogenesis, clinical aspects, diagnosisand therapeutic approach. The construc-tion of such a map is one of the majoraims of our Confederation.

The ECMM Executive Committee, inclose contact with the Council, has ap-proved the proposals for the constitu-tion of the first five Working Groups. Ithas appointed a convenor for each studyand has approved the regulations, whichestablish the organizational structure ofthe epidemiological working groups andensure that collaborators will be able towork in harmony while at the same timeeach one’s rights are respected. The reg-ulations are published on the next page.The Working Groups approved to dateare:

Survey of cryptococcosis in EuropeConvenor: Dr. Françoise Dromer

Survey of histoplasmosis in EuropeConvenor: Prof. E. Glyn V. Evans

Survey of nocardiosis and other aerobicactinomycetes infections in Europe

Convenor: Dr. Patrick BoironSurvey of candidemia in Europe

Convenor: Prof. Renée GrillotSurvey of tinea capitis in Europe

Convenor: Prof. Roderick J. Hay

In each Working Group the Convenorwill collaborate with a National Coord-inator in each country. The latter will beresponsible for stimulating the participa-tion of various researchers in that coun-

try in order to collect a sufficient num-ber of cases and collate, check and trans-mit the data to the Convenor. TheNational Coordinators are chosen by theConvenor, and candidates for this role inany of the above studies should prompt-ly inform the Convenor of his/her avail-ability.

A presentation of each study and theConvenor’s address are published in thefollowing pages. The name of theNational Coordinator can be obtainedfrom the Convenor or from the localECMM delegate (for the list of dele-gates, see page 2).

The respective case record forms forthe studies are also included. They havebeen designed based on previous experi-ences, and the aim was to make them asclear and simple as possible to facilitateparticipation. We suggest keeping thecopy of the printed forms as mastercopies that can be photocopied eachtime that a case is to be reported.

The form, with all sections complet-ed, should be sent to the local NationalCoordinator, together with the strainisolated in the studies only when diagno-sis is based on culture. “Ownership”ofthe strains will be protected according toparagraphs “Isolates” and “Authorship”of the «Rules for EpidemiologicalECMM Working Groups».

The planned duration of each study is2 years. However, at the ECMMCongress to be held in Glasgow in 1998,a special session will be reserved for thepresentation and discussion of the pre-liminary results of each study.

Maria Anna Viviani


The first number of the Newsletter coincides with the setting up of the first ECMM Working Groups,which are concerned with epidemiologicalmonitoring of fungal infections diagnosed in Europe.

EpidemiologicalWorking Groups of ECMM

Working Groups


AWorking Group is composed of aConvenor (appointed by the

Council), of several national coordinators(one in each country which wants to par-ticipate) and of local investigators.Convenor and coordinators have to bemembers of their national Society.

A study has to be approved by theCouncil on the basis of submission of ashort project outline making clear thebackground and the goals of the study.

The collection of data requires a formthat will be prepared by the Convenorwith the help of some experts in the field(including a statistician).When the form isready, an announcement will be made inthe ECMM Newsletter. This announce-ment will include a summary of the study,the form, and an application form allow-ing people who are interested in partici-pating to send their name, address, affilia-tion and country to the Convenor. Thosewho wish to be the coordinator of thestudy for their country will be able to ap-ply at the same time.

This will allow the Convenor to selectnational coordinators (no more than1/country) on the basis of their willingnessto participate and their expertise in thefield. Participants can also provide help inselecting the appropriate coordinator.

National coordinators will be respon-sible for collecting the forms, checkingthey are properly filled, helping local in-vestigators if necessary and forwardingthe forms to the Convenor. If a coordina-tor has to resign, the Convenor of thestudy will select another coordinator (andnot the other way around).

Convenor and coordinators can onlybe involved in one epidemiological studyfor the ECMM.

When the Group is formed (Convenor+coordinators), the Convenor has to informthe General Secretary of their names. He isalso expected to submit a progress report tothe General Secretary each year. TheGeneral Secretary is responsible for co-or-dinating the work of the different WorkingGroups.

The Convenor of a study has to check

with the local delegate or the administra-tion of his country if there are any regula-tions on data collection, especially when us-ing personal information on the patients.

IsolatesFor all the epidemiological studies, itwould be important to list centres (one orseveral) that will be able to collect thefungal isolates. This will allow a check onthe identification and storage of isolatesfor future studies.At the request of the depositor, the iso-lates will be maintained in a restricted col-lection, i.e. will not be sold or given outwithout authorization.If a subsequent study is designed that re-quires the use of isolates stored from aprevious study, all the mycologists whoparticipated initially will be invited to jointhe new group.

AuthorshipIt must be clear that all participants willco-author the paper published by theGroup. However, rules for authorshipshould be as follow• The Convenor will be the first author.• The coordinators will follow in a listranked by the number of forms collectedand, in case of equal contribution, in al-phabetical order.• The Study Group will sign last on behalfof the ECMM and the participants will belisted in alphabetical order of the countryand then in alphabetical order of the lastname for each country. Each coordinatorwill be responsible for the accuracy of thelist.• In case of a study involving isolates col-lected previously, the Study Group will in-clude the members whose isolates areused even if they do not participate in thesecond study.• Before submission to a Journal, the pa-per should be reviewed by all the coordi-nators and an agreement reached.Participants from each country will be in-formed by the coordinator. A copy of thefinal paper should be sent to the GeneralSecretary.

Rules for EpidemiologicalWorking Groups

Name first and family name

Title:

Address:

Country:

Phone:

Fax:

E-mail:

Working Groups


Epidemiological Survey ofCryptococcosis in Europe

Aim of the studyCryptococcosis, a life-threatening op-portunistic fungal infection, is notamong the diseases with mandatory no-tification around the world. This ex-plains why there is very little informa-tion concerning the incidence amonggroups at risk such as AIDS patients,cancer patients or organ transplant re-cipients. The natural history of crypto-coccosis is still not well known. Recentstudies have suggested that there are dif-ferences among the serotypes ofCryptococcus neoformans regarding thetype of host infected and the lesionscaused by the fungus.The main purpose of this ECMM studyis to collect information on the patientsinfected by C. neoformans and on the in-fecting serotypes. A simple form will al-low us to identify the risk factor(s), theextent of the dissemination at diagnosisand the initial treatment. Isolates willthen be serotyped and the data ana-lyzed.

Study designCases of cryptococcosis, for which the in-fecting isolate is available, will berecorded on a questionnaire (one-pagelong) and the corresponding isolate willbe serotyped in one of the reference lab-oratories.“Ownership” of the strains will be pro-tected accordingly to paragraphs“Isolates” and “Authorship” of the«Rules for Epidemiological WorkingGroups».Investigators interested in participatingto this study as “national coordinator”are requested to fill the following form.

ConvenorFrançoise Dromer, MD, PhDUnité de MycologieInstitut Pasteur25, rue du Dr. RouxF-75784 Paris Cedex 15, FranceTel/Fax: +33 1 4061 3389E-mail: [email protected]

Working Groups


© 1997 ECMM

EPIDEMIOLOGICAL SURVEY OF CRYPTOCOCCOSIS IN EUROPE

PATIENT DETAILS report first 3 and 2 letters of the names

Family name |__|__|__| First name |__|__| Year of birth |__|__|__|__| Sex: � M � F

Continent of birth: Country of residence:

(for America specify South, Central or North)

RISK FACTORS check all boxes needed

� HIV infection CD4/mm3 � Cryptococcosis = AIDS-defining disease

� Corticosteroid therapy (≥ 0.5 mg/kg/d) reason

� Autoimmune disease specify

� Organ transplantation specify organ

� Solid tumor/hematologic malignancy specify

� Bone marrow transplantation � Fludarabine treatment

� Diabetes mellitus � Cirrhosis

� Chronic renal failure � Local injury

� Contact with pigeons or other birds Other specify

� Unknown risk factor

DIAGNOSIS OF CRYPTOCOCCOSIS check all boxes needed

Date d/m/y � New case � Relapse

Suspected on the basis of: � clinical symptoms specify

� X rays, CT scan, NMR specify

� screening for antigen

Antigen detected � in serum titer / � in CSF titer � CSF pos.ve india ink

Cryptococcus neoformans cultured from:

� CSF � blood � BAL � urine � skin � not done � not done � not done � not done � not done

other specify

INITIAL TREATMENT check all boxes needed

� amphotericin B � 5-fluorocytosine � fluconazole � itraconazole

Other: Daily dose

CORRESPONDING CLINICIAN/MYCOLOGIST indicate name, address, phone and fax no., e-mail address

SIGNATURE DATE

Please, return the form together with the strain (specify from which sample it has been isolated), to your country’s coordinator.

Working Groups



Title:

Address:

Country:

Phone: Fax: E-mail:

Epidemiological Survey ofHistoplasmosis in Europe

BackgroundHistoplasmosis is a fungal infectioncaused by two dimorphic fungi,Histoplasma capsulatum var. capsulatumand H. capsulatum var. duboisii. The dis-ease caused by H. capsulatum var. capsu-latum (from now on referred to simplyas H. capsulatum) is a relatively commoninfection, endemic primarily in centraland eastern parts of North America andparts of Central and South America, butoccurring sporadically in many othertropical and subtropical countries worldwide. Exposure to H. capsulatum by in-halation of conidia causes a mild pul-monary disease or is asymptomatic. Inindividuals with pre-existing lung dis-ease or immunosuppression, this prima-ry infection may lead to a secondarychronic or disseminated infection, whichmay be fatal. The prevalence of the dis-seminated disease has increased with thespread of AIDS and the increase in thenumber of immunosuppressed patients(e.g. transplant) in recent years. H. cap-sulatum var. duboisii infection, calledAfrican histoplasmosis or histoplasmosisduboisii is endemic only in Central andSouthern Africa. It is a rarer disease thattends to cause subcutaneous and bonelesions and dissemination is rare.

Histoplasmosis in EuropeWhile not endemic in Europe, cases ofhistoplasmosis occur in individuals whohave lived or travelled in endemic areas.There is often a history of exposure, for

example, exploration of bat-infestedcaves. Reactivation of infections fromseveral years previous may result from afailing immune system, as for exampleoccurs in some AIDS patients. Chronicpulmonary histoplasmosis has also beenseen in the last two decades in individu-als who had not visited the endemic ar-eas since the time of the second worldwar (e.g. Burma, 1944-45). In a recentstudy in France, 81 cases of histoplasmo-sis were recorded between 1970-94 andH. capsulatum was the causal agent inthe majority of cases; in all cases, infec-tions were believed to have been ac-quired outside Europe. Accurate infor-mation of the general prevalence ofhistoplasmosis in Europe is not avail-able.

Objective of surveyThe objective of this survey is to discov-er the prevalence of histoplasmosis inEurope, where and how the infectionwas acquired, the groups at risk, the or-ganism responsible and the methods bywhich the infection was diagnosed. Thiswill lead to a better understanding ofthis imported mycosis and will enable aco-ordinated effort to target at risk pop-ulations and to standardize methods forthe diagnosis and treatment of the dis-ease.Investigators interested in participatingto this study as “national coordinator”for their country are requested to fill thefollowing form.

ConvenorE. Glyn V. Evans, PhD, FRCPathProfessor of Medical MycologyPHLS Mycology Ref. LaboratoryDepartment of MicrobiologyUniversity of LeedsUK-Leeds LS2 9JT United KingdomTel: +44 113 233 5600Fax: +44 113 233 5587E-mail:[email protected]

© 1997 ECMM

EPIDEMIOLOGICAL SURVEY OF HISTOPLASMOSIS IN EUROPE


Family name |—|—|—| First name |—|—| Year of birth |—|—|—|—| Sex: � M � F

Country of birth: Country of residence:


� HIV infection (CD4 /mm3...................) � Transplantation specify organ

� Corticosteroid therapy reason

� Hematologic malignancy/solid tumor specify

� Occupational (within last year)

Exposure to birds/bird droppings details

Exposure to bats/bat droppings details

� Travel or residence outside Europe (within last 5 years)

USA/Canada list states/provinces Dates

Other list countries Dates

� Other specify � No predisposing factors

DIAGNOSIS OF HISTOPLASMOSIS � New case � Relapse

Date of diagnosis d/m/y Date symptoms started d/m/y

Clinical symptoms specify

X rays, CT scan, NMR specify

Skin test � positive � negative � not done

Antibodies detected by � CF titre / � ID band H,M � not done

Antigen detected in � serum titre / � urine titre � not done

Histoplasma capsulatum var. � capsulatum / � duboisii cultured from:

� BAL/sputum � blood � CSF � urine � skin lesion� not done � not done � not done � not done � not done

other specify

Yeast cells seen in

� BAL/sputum � blood � CSF � urine � skin lesion� not done � not done � not done � not done � not done

other specify

TREATMENT

Antifungal(s) given daily dose duration (to date)


SIGNATURE DATE

Please, return the form together with the strain, if available (specify from which sample it has been isolated), to your country’s coordinator.

Working Groups


Aim of the studyThere are few studies that address ade-quately either the epidemiology or theincidence of nocardial infections in hu-man and animal populations. Since noagency or organization monitors dis-eases caused by Nocardia spp., the inci-dence of infections by these filamentousbacteria remains unknown. However, byanalyzing the literature, some idea of theimpact of nocardial infections on hu-mans and animals is emerging. In addi-tion, outbreaks of nocardiosis are de-scribed in several countries. Moreover,over the past 20 years, more reliablemethods for classifying bacteria have re-fined the taxonomy of the actino-mycetes. Consequently, many taxa for-merly included in the genus Nocardiahave been reclassified, while new specieswere discovered.The other aerobic actinomycetes(Rhodococcus, Gordona, Tsukamurella,etc.) are also important potential causesof serious human and animal infections.However, because they are infrequentlyencountered in clinical practice, very lit-tle is known about these infections. Thedifficulties of diagnosis can lead to anunderestimation of their real prevalenceand incidence.An improved understand-ing of the epidemiology and pathogene-sis of these infections will emerge whenlaboratories from different countriescollaborate in an international epidemi-ological survey.Because most members of the genusStreptomyces are saprophytes, their sig-nificance in clinical microbiology is gen-

erally overlooked. However, Streptomycesspp. are commonly isolated from humansamples and several species are consid-ered to be of potential medical impor-tance. Several reports of Streptomycesinfections have included septicemia andprimary lung involvement, panniculitis,brain abscess, and cervical lymphadeni-tis. Evidence is growing thatStreptomyces spp. should be added to thelist of opportunistic organisms.The main purpose of this ECMM studyis to collect information on the patientsinfected by Nocardia spp. and other aer-obic actinomycetes, and on the infectingisolates. A simple form will allow theidentification of risk factors, the extentof the dissemination at the moment ofdiagnosis, the initial treatment, etc.Isolates will be (re)identified using clas-sical and new molecular methods(PCR), and extensively characterized bymeans of various analyses includingmolecular typing (RAPD), plasmidanalysis, in vitro antibiotic susceptibilitytesting, enzymatic characterization, po-tential pathogenic factors, etc.

Study designCases of nocardiosis and other aerobicactinomycetes infections, for which theinfecting isolate is available, will berecorded on a one-page questionnaireand the corresponding isolate will be ex-amined and characterized.Investigators interested in participatingto this study as “national coordinator”for their country are requested to fill thefollowing form.

Working Groups


Epidemiological Survey ofNocardiosis and other AerobicActinomycetes Infections in Europe

ConvenorPatrick Boiron, PhcyD, PhDUnité de MycologieInstitut Pasteur25, Rue du Dr. Roux F-75724 Paris Cedex 15, FranceTel.: +33 1 4061 3255 Fax: +33 1 4568 8420 E-mail: [email protected]


Title:

Address:

Country:

Phone: Fax: E-mail:

© 1997 ECMM

EPIDEMIOLOGICAL SURVEY OF NOCARDIOSISAND OTHER AEROBIC ACTINOMYCETES INFECTIONS IN EUROPE(except Mycobacteria)



Continent of birth: for America specify South, Central or North

Country of residence Work


� Organ transplantation specify organ

� Corticosteroid therapy reason

� Chemotherapy specify

� Predisposing pulmonary disease specify

� HIV infection (CD4 /mm3 ) � IV drug abuse

� Other specify � No predisposing factor

DIAGNOSIS OF INFECTION check all boxes needed

Date d/m/y � New case � Relapse

Strain identification

Strain cultured from:

� BAL � sputum � CSF � pus specify

� biopsy specify � other specify

Positive direct microscopy � specify � not done

Positive histology � specify � not done

Main clinical, biological, radiological signs

Site of infection: � lung � brain � skin � other specify

ANTIBIOTIC TREATMENT check all boxes needed

Empiric treatment � specify daily dose

Specific therapy � specify daily dose

Cured � yes � no if not, specify

Life long suppressive therapy � yes � no specify


SIGNATURE DATE

Please, return the form together with the strain, if available (specify from which sample it has been isolated), to your country’s coordinator.

Working Groups


Aim of the studyIn order to better appreciate the currentrole of bloodstream infections due toCandida and Torulopsis spp. in hospital-ized patients (cancer and non-cancerpopulations), ECMM has decided to de-velop a study, collecting information atthe European level.Indeed, there is a great need to increasethe awareness of medical and biologicalpractitioners who are still underestimat-ing morbidity and mortality related tocandidemia. High-quality clinical re-search in the difficult field of these fun-gal infections requires objective analysisof the epidemiological situation from alarge multicenter study.The main purpose of this survey is to in-tegrate at the European level, in a sim-ple form, information on cancer andnon-cancer patients suffering fromproven candidemia and concerning (i)the causative organisms of candidemia,the potential emergence of unusualspecies and the sources of the infection,(ii) the major underlying risk diseases or

factors, (iii) the blood culture methodsmost often used in Europe to detectbloodstream pathogens, (iiii) the initialapproach to management of a docu-mented candidemia and the outcome ofthe disease.Phenotypic (mycological profile and an-tifungal susceptibility testing) and geno-typic studies on the isolates will be per-formed centrally.

Study designCases of documented candidemia will berecorded on a questionnaire (two-pagelong). The form and the correspondingisolates will be centralized in one nation-al laboratory and the strains studied inreference centres.“Ownership” of the strains will be pro-tected accordingly to paragraphs“Isolates” and “Authorship” of the«Rules for Epidemiological WorkingGroups».Investigators interested in participatingto this study as “national coordinator”are requested to fill the following form.

Working Groups


Epidemiological Survey ofCandidemia in Europe

ConvenorRenée Grillot, PhDProf. of Parasitology and MycologyService de Parasitologie-MycologieCHU de GrenobleHôpital Michallon, BP 217F-38 043 Grenoble Cedex 9FranceTel: +33 4 7676 5350Fax: +33 4 7676 5660E-mail:[email protected]


Title:

Address:

Country:

Phone:

Fax:

E-mail:

Working Groups


© 1997 ECMM - EORTC

EPIDEMIOLOGICAL SURVEY OF CANDIDEMIA IN EUROPE(Candida & Torulopsis species and their perfect form)



Country & city of residence Hospitalization date d/m/y

RISK FACTOR/PREDISPOSING DISEASE check all boxes needed

� General surgery site of surgery date d/m/y

� Organ transplant specify organ date d/m/y

� Burn % of burned body surface date d/m/y

� HIV infection (CD4/mm3 )

� Fetal immaturity birth weight weeks of gestation

� Intensive care date of admission in ICU d/m/y � single/� multiple bedroom

� Antibiotics given within 2 weeks prior to blood yeast detection � IV � PO

type(s)/total dose

� Corticosteroids given at any time during the month prior to yeast detection in blood (exclude given with

amphotericin B) specify reason

type(s)/total dose

� Hematological disease/solid tumor specify diagnosed d/m/y

Disease stage at time of candidemia: � onset � complete/ � partial remission

� resistant � relapse � other specify

Last therapy for underlying disease: started d/m/y

� 1st/ � 2nd line chemotherapy � auto/ � allo BMT

� maintenance � other specify

� Radiotherapy/ � surgery within 1 month prior to candidemia (last done d/m/y )

� Other specify

DIAGNOSIS OF CANDIDEMIA check all boxes needed

Date of the first positive blood culture d/m/y � 1st episode � relapse

Blood puncture from � catheter � vein

Blood culture system on which candidemia was diagnosed:

� Lysis centrifugation

� Bactec system medium

� other system medium

� combination specify

Species identified Other fungus/bacteria isolated specify

Date of the last positive blood culture d/m/y

Total number of positive blood cultures/total number of blood cultures /cont’d

Working Groups


Candidemia page 2

OTHER CANDIDEMIA INFORMATION check all boxes needed

IV line

IV line in situ at time of the first positive blood culture � no � yes

� central venous catheter � peripheral date of IV line placement d/m/y

IV line removed after the diagnosis of candidemia � no � yes

Catheter cultured � no � yes negative � yes positive

� same yeast species � other fungus/bacteria

Clinical & biological signs at time of candidemia

� Shock related to candidemia

� Organ involvement specify organ

Documented: � clinically � histologically � by X-ray, CTscan, NMR

White blood cell count/mm3

Candidemia associated with:

� seroconversion increasing of � antibody titre (>2 dilutions)/� bands

� antigenemia specify test and titre

Candida colonization, due to the same species, detected within 2 weeks prior to outcome of candidemia on

� oral mucosa � resp. tract � GI tract � GU tract � vagina � skin� not done � not done � not done � not done � not done � not done

other specify

Antifungal(s) given within 2 weeks prior to candidemia: reason

type of antifungal � PO � IV daily dose

Initial treatment of candidemia

� amphotericin B � 5-fluorocytosine � fluconazole � itraconazole

other: daily dose

Outcome (day 30): � survival � candidemia related complications � death

CORRESPONDING CLINICIAN/MYCOLOGIST indicate name, address, phone and fax no, e-mail address

SIGNATURE DATE

Please, return the form together with the strain (first isolate) to your country’s coordinator.

Working Group


Recent informal discussions amongstEuropean mycologists suggest that insome countries there has been a recentshift in the pattern of tinea capitis infavour of anthropophilic species.The ob-jective of this survey is to identify theprinciple causes of tinea capitis in differ-ent European countries over a one yearperiod - 1997-1998. It would be helpfulto compare data from these years withany historical material and, if possible(ideal but not essential), collaboratingcentres should provide similar data from1987-1988. The accuracy of the surveydepends on the availability of laboratoryconfirmed diagnoses and participationin this survey would therefore be of po-tential interest to microbiologists/mycol-

ogists or dermatologists with access todiagnostic laboratory facilities.As the numbers of patients are likely tobe substantially higher than in the otherECMM surveys we have had to follow adifferent procedure for gathering dataand at this stage we are hoping to identi-fy all those who would be interested inparticipating in such a study.

We would like hear from all interestedindividuals or groups and, based on thisinitial call, would develop the data gath-ering exercise with as many as possibletaking into consideration the need to ob-tain representative information fromdifferent regions in Europe.

ConvenorRoderick J. Hay DM FRCP FRCPath Professor of Cutaneous MedicineSt John’s Institute of DermatologyMedical and Dental SchoolGuy’s HospitalSt. Thomas StrUK-London SE1 9RTTel/fax +44 171 955 4687

Epidemiological Survey ofTinea Capitis in Europe

1. Name of Centre 2. Idnum (Leave blank)

3. Contact person and address:

4. Population served: � Urban � Rural � Mixed

5. Usual source of material received in laboratory/clinic:

� Reference cultures only � Routine diagnostic cultures only � Mixed routine and reference

6. Approximate numbers of patients with confirmed diagnosis of tinea capitis or cultures from tinea capitis

seen/received each year:

Thank you for your interest.Please return to Professor R.J. Hay

Session I


Special report on...

3rd International Conference on

Cryptococcus andCryptococcosis

The Cryptococcus and Cryptococcosis Conference is awell recognized scientific appointment which everythree years presents the state of the art of this area ofmedical mycology. We have asked a chairman of each session to report briefly on recent advances presented and discussedduring the meeting. We are pleased to be able to give awell delineated and exciting picture, a realmonography, of all the aspects of this discipline. Weare grateful to our colleagues for their invaluable,generous collaboration.

The opening lecture given by Prof. E. Drouhet and the closingremarks by Prof. F. Staib will bepublished in the forthcoming issueof the Journal de MycologieMédicale.

The third InternationalConference on Cryptococcus

and Cryptococcosis was held at thePasteur Institute in Paris onSeptember 22-26, 1996. The meet-ing was organized by F. Dromerand B. Dupont from the PasteurInstitute, and K.J. Kwon-Chungfrom the National Institutes ofHealth in Bethesda. It took place inthe new complex built recently af-ter the donation of the Duchess ofWindsor. The scientific communityinterested in Cryptococcus andcryptococcosis has increased in sizeover time (100 attendees inJerusalem in 1989, 188 in Milano in1992 and 205 in Paris). More than50 oral communications and 62posters presented by scientistscoming from all over the worldwere presented on topics covering

molecular biology and biochem-istry, taxonomy, epidemiology andecology, immune responses, patho-genesis, drugs and therapy, clinicalmanifestations and diagnosis, andcryptococcal polysaccharide. Themeeting, summarized in the ab-stract book, and below by the per-sons chairing the correspondingsessions, offers a comprehensiveview of the current knowledge onthe disease and the fungus.The result of the ballots collectedduring the meeting was announcedat the end of the gala dinner at theMusée du Louvre. We are all en-thusiastic to know that London willheld the 4th Conference that willthus be organized by R.J. Hay andhis colleagues in 1999.

Françoise Dromer

Scientific program of the thirdInternational Conference onCryptococcus and Cryptococcosisopened with the molecular biologyand biochemistry session. Therewere a total of nine invited talks inthe session; six on molecular biolo-gy and three on biochemistry. Sincethe transformation system was de-veloped for C. neoformans in 1990,work on molecular biology of theyeast has proceeded on dissectingvirulence factors, identification ofdrug targets and other importantbiological aspects of this pathogen.Drs. J.C. Edman and B.L. Wickespresented their works on theMATα locus and the MATα specif-ic dimorphism. It was shown thatthe MATα locus of C. neoformansis significantly larger than any mat-ing type loci known from other fun-gi and the locus is unique in that inaddition to containing the expectedgenes for pheromone and home-odomain boxes, it is closely linkedto at least two genes involved insignal transduction events. Thepheromone gene induces a fila-mentous response when introducedinto MATα strains. MATα strainsalone can produce hyphae and ba-sidiospores when cultured undercertain conditions such as low con-centration of carbon source, devoidof ammonia, dry substance (4%agar) and 25°C incubation temper-ature. Such phenomenon termedhaploid fruiting or monokaryoticfruiting is common in basid-iomycetes but only in C. neofor-mans it appears to be a mating typespecific phenomenon. Since MATαstrains are known to be more viru-lent than MATa strains, theseMATα specific genes may be asso-ciated with regulation of other vir-ulence genes such as CNLAC1 orcapsule genes.

Drs. S.D. Salas and P.R.Williamson both presented molec-ular aspects of the CNLAC1 geneencoding a laccase which is knownto be an important virulence factorof C. neoformans based on previousgenetic studies. Molecular evidencethat the melanin forming ability ofC. neoformans is an important viru-lence factor was presented by Dr.

Salas. He showed that virulence ofa CNLAC1 deleted isolate is signif-icantly reduced compared to a wildtype or a melanin negative mutantcomplemented with the wild typeCNLAC1 gene. The copper bindingsites of the CNLAC1 gene seem tobe critical for laccase function sincea missense mutation in one of thefour putative copper binding sitesof the gene abolished melaninforming ability. Dr.Williamson ana-lyzed the 5’ region of the CNLAC1gene and showed that there is aTATA box at position -539, up-stream from the first translationsite (ATG start codon) which couldprovide the DNA binding site for atranscription factor TFIID, CAATbox at position -503 and Sp1 site atposition -1727. Electrophoretic mo-bility shift assays performed withnuclear extracts obtained from C.neoformans grown under repressed(glucose) as well as a derepressedconditions for laccase activity sug-gested that there are nuclear pro-teins that bind to these sites. Thefunctional role of the Sp1 site in re-lation to CNLAC1 remains to beelucidated. Plasmids containing in-serts of sequentially deleted 5’ re-gions were transformed into a cn-lac1 mutant strain in which the 5’segment of CNLAC1 completelydeleted. It was observed that trans-formants with plasmids containingthe putative TATA box alone pro-duced high levels of pigment whiletransformants with only open read-ing frame of CNLAC1 showed nopigment. Glucose repression wasreduced when the sequence up-stream of -837 was removed. Thesedata indicated the involvement ofdifferent segments of the 5’ primeregion in the regulation of CN-LAC1 expression.

Dr. J.R. Perfect reviewedprogress in molecular biology of C.neoformans briefly and discussed amolecular model for potential anti-fungal target genes such as ADE2(phosphoribosyl aminoimidazolecarboxylase), NMT (N-myristoyltransferase), genes occuring in thesignal transduction pathway, andtopoisomerases I and II. ADE2 is ahighly conserved house-keepinggene essential for growth of the or-ganism but it may be possible to de-sign specific inhibitors of the fungalADE2 protein with no effect on ho-mologous host proteins. This is dueto the fact that the C. neoformansADE2 protein has bifunctional cat-alytic enzyme activity and its inter-mediate structure is absent in thehuman purine pathway. Also dis-cussed was an indirect approach forthe identification of potential viru-lence genes and drug targets bycomparing up-regulated and down-regulated genes in C. neoformansduring infection of the central ner-vous system. At the present time,Dr. Perfect has identified fourgenes that are up-regulated withinthe CSF and the importance ofthese genes to virulence is being in-vestigated.

Dr. J.N. Galgiani has identified aprotein of approximately 20 kDafrom culture filtrates of C.neoformans which stimulates aCryptococcus-specific DTH re-sponse in mice. His laboratory is inthe process of cloning the cDNA ofthis protein for the production ofrecombinant protein which canelicit a cell mediated immune re-sponse in mice immunized withcryptococcal antigens. There is apossibility that this protein may bea protease secreted by the fungus.

Of the three biochemistry pa-

Special report


chaired by K.J. Kwon-Chung and J.R. Perfect

Molecular biologyand biochemistry

Session I

Special report

pers, two were on antioxidativeagents and one was on azole resis-tance. The first was presented byDr. E.S. Jacobson who discussedthe oxidation-reduction bufferingby cryptococcal melanin. Hedemonstrated sequential reductionand oxidation of melanin and itsmodulation by Fe(II) using twotypes of modern electrochemicaltechniques: the potentiometricmethod in estimating the ratio ofoxidized to reduced residues inmelanin and the voltammetricmethod to deduce the oxidationstate of melanin from the quantityof electrons which is able to accepta standard reduction scan. Amelanin film generated fromsaponified 5,6-diacetoxyindole bycyclic voltammetry was used formeasurements of oxidation and re-duction. This study demonstratedthat melanin is a redox buffer orelectron exchanger.

Dr. S. Kelly studied possible bio-chemical causes of azole resistancein C. neoformans strains isolatedfrom AIDS patients by examiningthe biochemical basis of variationin azole susceptibility and testingthe potential for cross-resistancebetween azole and polyene anti-fungals. He found that the patternof sterol accumulation in C. neofor-mans following azole treatmentwas different from that ofSaccharomyces cerevisiae. Unlikethe response in azole treated S.cerevisiae which accumulates lanos-terol, obtusifoliol, 14α-methyl fe-costerol and 14α-methyl-3,6-diol,C. neoformans accumulated eburi-

col and obtusifolione, indicating ablock at the C4 demethylation stepof 14α-methylated sterols. This sug-gests that sterol ∆5(6) desaturationmay be inhibited in C. neoformanswhile this reaction is not inhibitedin S. cerevisiae or Candida albicans.Mutants of C. neoformans withcross-resistance to azole and poly-ene antifungals are readily isolatedat a frequency of 10-8, suggesting asingle mutation responsible forcross-resistance. The mechanism ofcross-resistance does not appear tohave been associated with ergos-terol biosynthesis. Rather, de-creased uptake and increased ef-flux of the drug are the likely mech-anism in these mutants. On the oth-er hand, four mutants isolated fromAIDS patients in whom flucona-zole therapy failed showed cross-resistance to other azoles (itra-conazole and ketoconazole) butwere not resistant to polyenes. Inthese strains, the microsomal sys-tem was typical of fungi. Althoughthey showed slightly elevated P450content and slightly reduced azolelevels in cells, the clear cause of re-sistance in these strains appearedto have been the nature of thesterol 14α-demethylase. The en-zyme isolated from these strainswas more resistant to azoles thanthat from a wild type when testedin cell free systems. These resultsindicated the existence of a widerange of biochemical causes ofazole resistance in C. neoformans.

Dr. V. Chaturvedi presented ev-idence that the production and ac-cumulation of mannitol contributes

to the tolerance of fungal cells toheat, osmotic stresses and reactiveoxygen intermediates (ROIs). Hestudied a mutant strain of C. neo-formans isolated by mutagenesiswhich produces and stores signifi-cantly decreased amount of manni-tol than its parental strain. In a pre-vious work, this mutant was shownto be more susceptible to growthinhibition, killing by heat and highsodium chloride concentration, andhave significantly decreased viru-lence in mice than the wild typestrain. Since classical genetic analy-ses of this mutant did not succeedand a mannitol mutant isolated bygene disruption is not available, aglycerol-defective, osmosensitive S. cerevisiae mutant Osg1-1 wasused to show the effect of mannitol.The mutant Osg1-1 was trans-formed with a multi-copy plasmidcarrying Escherichia coli mtlD genewhich encodes mannitol phosphatedehydrogenase. The S. cerevisiaetransformant not only synthesizedmannitol but restored osmotoler-ance in the strain.The transformantwas less susceptible to killing by hy-droxy radical and other ROIs. Thisstudy demonstrates in vivo thatmannitol scavanges ROIs. There isa possibility that mannitol protectsC. neoformans cells from killing byhuman neutrophils and thus con-tributing to virulence.

K. June Kwon-Chung


Session IIchaired byD.H. Ellis and E. Guého

Taxonomy,epidemiology, andecology

Dr. K.J. Kwon-Chung openedthe session with an excellent reviewon the genus Filobasidiella whichcontains two unique species, F. neo-formans (anamorph C. neoformans)and F. depauperata (no ontogenicyeast state known). Although thesetwo species share nearly identicalbasidial morphology they have dis-tinct life cycles, physiology andecology. Of particular interest is thefinding that F. depauperata is thefirst basidiomycetous fungus foundto have its 5S rRNA genes dis-

Special report

persed throughout the genome,whereas in F. neoformans the 5SrRNA gene is located within therDNA repeat unit. Thus the genusFilobasidiella is the first eumycoticgenus found to have two distinctgenomic arrangements of the 5SrRNA gene.

Dr. R. Petter then presented apaper examining the molecular di-vergence of the virulence factors ofF. neoformans found in other heter-obasidiomycetes. The phylogenetictree construct on the basis of 17SrRNA sequences suggests proximalevolution of Filobasidiella andTremella species and can best beclassified in the order Tremellales,members of which produce encap-sulated yeasts during their haploidstate. A number of closely relatedmembers of the Tremellales werethen screened for homologues oftwo virulence genes found in C.neoformans, viz the capsule geneCAP59 and the melanin biosynthe-sis gene CNLAC1. The remainderof the session concentrated on theepidemiology and ecology of C.neoformans especially on the use ofmolecular characterisation of iso-lates which has proved to be a valu-able epidemiological tool.

Dr. S. Kohno utilised bothRFLP and RAPD methods to fin-gerprint clinical and environmentalisolates of C. neoformans var. neo-formans from Japan. He concludedthat both clinical and isolates frompigeon excreta belonged to thesame fingerprint type which pro-vides additional evidence linkingthis environmental reservoir toclinical disease.

Dr. F. Dromer reported on thehigh incidence of C. neoformansvar. neoformans serotype D infec-tion in France (21% of isolates)and Italy (49% of isolates). A de-tailed analysis of 456 cases of cryp-tococcosis taking into account pre-disposing condition, age, sex and in-fection site suggested differences interms of ecologic niche, virulenceor tropism between serotypes Aand D. The risk of being infectedwith a serotype D isolate was sig-nificantly higher in some areas ofFrance and among patients withskin lesions and those receiving


Session IIIchaired by

J. W. Murphy and L. Polonelli

Immune responsesin cryptococcosis

prolonged courses of corticosteroidtherapy. Genetic similarities utilis-ing DNA fingerprinting betweenclinical and environmental isolateswere also demonstrated. Finally,differences in antifungal suscepti-bility were also found betweenserotype A and D isolates with theformer being more resistant totherapy.

Dr. D. Ellis reviewed the world-wide distribution of C. neoformansvar. gattii and reported on two newhost eucalypt trees, Eucalyptus rud-is and E. gomphocephala. The pre-vious known host trees were E.camaldulensis and E. tereticornis.

Dr. M.T. Montagna et al. also re-ported the isolation of C. neofor-mans var. gattii from E. camaldu-lensis growing in Apulia, Italy.Further investigation of the rangeof host eucalypts for this fungus are

warranted and detailed methodsfor the isolation of C. neoformansvar. gattii were also presented.

Dr. D. Swinne highlighted therole of animals in the ecology andepidemiology of C. neoformans es-pecially the association ofserotypes A and D with pigeon andcanary droppings. Other ecologicalniches such as hollows in trees andthe potential for animal vectorswere also discussed for both C. neo-formans var. neoformans and C.neoformans var. gattii.

Finally, Dr. T.C. Sorrell present-ed data from 151 patients reportedto the Australasian cryptococcalstudy group in the year to March,1995.

David H. Ellis

The major focus of this sessionwas on induction, expression, andregulation of cell-mediated im-mune (CMI) mediated resistancemechanisms against C. neoformans.The first two presentations provid-ed information on direct interac-tions of lymphocytes with C. neo-formans. NK cells from cryptococ-cosis patients with and withoutHIV infection were found to havereduced anticryptococcal activity.Treatment in vitro with IL-12 re-stored NK cell anticryptococcal ac-tivity in NK cells from HIV+ pa-tients but did not upregulate anti-cryptococcal activity of NK cellsfrom a limited number of non HIV infected individuals (R.G.Washburn).

Human and mouse T cells di-rectly bind and kill C. neoformans

and such T cell activity can be aug-mented in the mouse by immuniza-tion with heat-killed C. neoformansor by treatment of T cells with im-mobilized anti-CD3. Enhanced Tcells with direct anticryptococcalactivity did not correlate with pro-tection (J.W. Murphy).

Several presentations coveredcytokine and chemokine require-ments for protection in cryptococ-cosis (G. Bancroft; M.F. Lipscomb,and G.B. Toews). Blocking of cy-tokines and chemokines such asIFNγ, TNF, MIP-1α, GM-CSF inthe mouse model influences pro-gression of cryptococcosis (G.Bancroft).

The type of TH cells inducedand the cytokines influencing theinduction and the relationship toseverity of disease were defined in

Special report

endothelial cells than the encapsu-lated forms. Internalisation,though, is needed for intracellulardamage to take place; this effect ismediated through a heat labilemechanism. In contrast IFN-γ pro-tects endothelial cells against cryp-tococcal mediated damage.

Interestingly Dr. A. Verheul andcolleagues have shown that both in-tact C. neoformans and purifiedgalactoxylomannan (GalXM) andmannoprotein (MP) components ofthe cell envelope can induce TNF-αproduction by macrophages. Therole of the purified components de-pends on a heat stable mechanism.The MP, but not GalXM, in addi-tion to both encapsulated and non-encapsulated C. neoformans en-hance HIV replication in peripher-al blood macrophages.

In studying the effects of C. neo-formans on activation of CD4 andCD8 lymphocytes Dr. C.H. Modyshowed that progression of CD8cells beyond late G1 required thepresence of CD4 cells. In additionphagocytosis is required for lym-phocyte proliferation, an event

This section of the meeting wasconcerned with the interaction be-tween cryptococcus and differenthost cells. In the first talk Dr. E.Blasi described the interaction be-tween glial cells and yeasts.Cryptococcus neoformans is phago-cytosed and destroyed by mi-croglial cells in mice through nitricoxide mediated pathways. Certaincytokines such as IL-6 and IL-1βenhance destruction of C. neofor-mans in vivo in a mouse model. Anavirulent Candida albicans straincan be given prior to challenge withvirulent C. albicans to produce pro-tection; however it does not protectagainst C. neoformans even thoughthere are high levels of IL-1β andNO synthase mRNA being ex-pressed. In contrast to the situationwith Candida, after cryptococcalchallenge there is delayed expres-sion of IL-6 which may indicate im-munomodulation by the encapsu-lated cryptococci.

Dr. J.E. Edwards described an-other potential effect of the capsuleas more acapsular isogenic or mu-tant cryptococci are internalised by


Session IVchaired by J.E. Edwards and R.J. Hay

Pathogenesis andhost responses

mouse models (M.F. Lipscomb andG.B. Toews).

Cryptococcal polysaccharide incirculation has been shown previ-ously to down regulate immune re-sponses. Data were presenteddemonstrating reversal of this com-plex cascade of suppressor cellsand factors could be achieved bytreating mice with activated anti-gen presenting cells pulsed withGXM (R. Blackstock).

Enhanced anticryptococcal ac-tivity of macrophages treated withchloroquine was reported. Themechanisms of chloroquine en-

hanced anti-cryptococcal activity ofmacrophages was shown to be dueto the chloroquine increasing thepH in the phagolysosomes of themacrophages (S.M. Levitz).

Finally antibodies to C. neofor-mans cytoplasmic antigens weredescribed in sera from 20 patientswith C. neoformans var. neofor-mans and 15 patients with var. gat-tii infections (A.J. Hamilton).

Juneann W. Murphy

which is inhibited by capsular ma-terial either in situ or presented in apurified form. However prolifera-tion can be reversed by anticrypto-coccal capsular antibody demon-strating a potential mechanism forantibody in host defence againstcryptococci.

In this section of the symposiumnew interactions between crypto-cocci and host cells which are in-volved in the pathogenesis of cryp-tococcosis have been described.The contributors have demonstrat-ed different roles for the capsuleand its components from inhibi-tion, partial or total, of immunepathways and uptake of cryptococ-ci to opsonisation of cells throughanticapsular antibody.

Roderick J. Hay

Special report

This session included a review ofcurrent treatment recommenda-tions and also speculations on po-tential future treatment regimensusing combinations of multipledrugs. In his opening presentation,Dr. W. Dismukes noted that at hisuniversity between 1990 and 1996there were 91 cryptococcosis pa-tients with HIV infection, but also asubstantial number (58 patients)without HIV infection. The majori-ty in both groups had meningitis,and in the non-HIV group the ma-jor predisposing factor appeared tobe the use of corticosteroids. Sincethe advent of the amphotericin B-fluconazole sequential therapy forAIDS patients with cryptococcalmeningitis, there has been less uni-formity in approach to patientswithout AIDS. In the Alabama se-ries there were 25 with meningitis,24 with pulmonary disease, 3 withboth, and 6 patients with otherforms of disease. Treatment regi-mens included amphotericin Balone (13), combined with flucyto-sine (13), fluconazole alone (17) orfluconazole combined with flucyto-sine (3). Of those with pulmonarydisease, 12 of 20 given ampho-tericin B ± flucytosine responded,versus 9 of 11 given azoles respond-ed. There was only 1 relapse.

Standard therapy for cryptococ-cal meningitis in patients withoutAIDS has consisted of 4 to 6 weeksof amphotericin B (0.3 mg/kg/day)and flucytosine (>100 mg/kg/day).On the basis of the good results of the California CooperativeTreatment Group with an oral reg-imen of fluconazole and flucytosinein patients with AIDS, the MycosesStudy Group sought to comparesuch an oral regimen with initial


Session Vchaired by

J.R. Graybill and D. Webb

Drugs and therapy for cryptococcosis

treatment with amphotericin B andflucytosine followed by fluconazole800 mg/day for 10 weeks (Pappas etal Abstract 73, Abstracts of the ID-SA 34th Annual Meeting, NewOrleans, 1996). Of 7 patients giventhe amphotericin B regimen, 6were successfully treated, with fol-low up at one year, there was 1 fail-ure and no deaths. However, of 5patients on the oral regimen, therewere 2 successes at end of treat-ment and one at one year. The oth-er 4 patients died, including 2deaths on treatment. Even thoughthe numbers did not permit analy-sis, the study was terminated afterthe second death. Dr. Dismukesconcluded that while a full courseof amphotericin B and flucytosinewas inconvenient and toxic, andthat while part of the course maybe shifted to fluconazole, there waslittle support to commencing withan all oral regimen.

Dr. R.A. Larsen reviewed a re-cently completed study of theCalifornia Cooperative TreatmentGroup, in which patients were esca-lated in cohorts with 400 mg incre-ments from 800 mg through 2000mg/day fluconazole. Within eachcohort patients were randomizedto no additional therapy or flucyto-sine. Responses were as reported inthe table, defining success as con-version of CSF culture.

These data demonstrated both adose response to fluconazole andan increased response when flucy-tosine was added.

Dr. B. Dupont reviewed theavailable data on prevention ofcryptococcosis and maintenancetherapy in AIDS and non-AIDSpatients. A variety of publishedsources concurred that fluconazole,given either for thrush or crypto-coccosis prophylaxis, was highly ef-fective. Despite the wide use of flu-conazole in France, however, thereappeared to be little effect on thenumber of yearly cases reported tothe French National ReferenceCenter for Mycotic Diseases.This issurprising in view of recent datafrom the USA indicating a signifi-cant decline in cryptococcosis cases(1996 ICAAC). Many of us in theUSA have experienced this (in myinstitution in San Antonio we haveseen >50% decline in annual cas-es), and most attribute it to wide-spread use of fluconazole. Dr.Dupont concluded by noting thatcryptococcosis in non-HIV patientsis sufficiently rare to preclude pri-mary prophylaxis. For secondaryprophylaxis in non-AIDS patientsthere are few data, and Dr. Dupontrecommended fluconazole at 200mg per day for as long as any im-mune deficit persisted.

Finally, Dr. G. Just-Nübling pre-

Fluconazole Fluconazole/flucytosine

Fluconazole dose N % Resp N % Resp

800 mg 9 11 8 751200 mg 16 37 8 871600 mg 16 62 16 692000 mg 8 62 8 87

Special report

sented a provocative open trialwith a “triple regimen” of ampho-tericin B, flucytosine, and flucona-zole conducted over 9 years. Themedian dose of amphotericin Bwas 930 mg/patient.Thirty eight pa-tients received flucytosine at a me-dian actual dose of 108 mg/kg/day,and 37 received fluconazole at 400mg/day. Duration varied from 1through 8 weeks. A complete re-sponse (clinical and negative CSFculture) was seen in 36/40 evalu-

able patients, and there were 3 par-tial responses and 1 failure.Two pa-tients stopped because of toxicity.This trial impressed me for the highdesired dose (150 mg/kg/day offlucytosine) and the general goodtolerance of treatment. Also, theoverall response of 90% is impres-sive, even higher than that claimedby the Mycoses Study Group in itsrecent trial of initial therapy withamphotericin B ± flucytosine.

Direct comparison is not possi-

ble because the conditions of thetreatment (drug doses/duration,etc) were rather different.However, unpublished murine databy Larsen, Graybill, et al, suggestthat triple drug therapy is superiorto 2 drug treatment. Thus, Dr. Just-Nübling’s approach may be reason-able.

John R. Graybill


Session VI

ineffective. Dr. Bennett thus em-phasized the importance of cere-bral imaging, when dementia isseen at any time during the courseof cryptococcosis, and the impor-tance of shunting, whatever the du-ration of the hydrocephalus hasbeen, since there was no correla-tion between duration of symptomsand neurologic recovery.

Dr. R.J. Hay then spoke aboutextrameningeal cryptococcosis. Hefocused his talk on cutaneous cryp-tococcosis, describing and showingthe various clinical and histologicallesions encountered. Skin infectionoften reflects dissemination (in50% of the cases for non-AIDS pa-tients and almost all AIDS pa-tients). Lesions can be solitary ormultiple, following direct inocula-tion or fungemia, but a solitary le-sion can be seen during disseminat-ed cryptococcosis. Of note and stillunexplained is the frequent associ-ation between C. neoformansserotype D and cutaneous lesions.

Dr. B.R. Speed reported theAustralian data on cryptococcosisdue to variety neoformans and va-riety gattii. Several parameters dif-

fer between the two varieties. Thehost preference is the most obviousdifference since var. neoformans in-fects immunosuppressed patientswhether infected or not by theHIV, whereas var. gattii is the mainagent of cryptococcosis in immuno-competent hosts (74-80%).

Meningitis is more frequent inpatients infected with var. gattii.Moreover, cerebral and pulmonaryinvolvement associated with nodu-lar lesions are more frequent.However, CT scan or MRI abnor-malities can be seen during infec-tions with both varieties. Infectionswith var. gattii are often difficult tocure by medical therapy alone andtherefore often require surgery.The mortality rate is somewhatlower than with var. neoformanswhich can be related to the immunestatus of the host but sequelae aremore frequent. Interestingly, pa-tients infected with var. gattii had agreater antibody response thanthose infected with var. neofor-mans, further supporting the ideaof differences in host response tothe two varieties.

Detection of cryptococcal anti-gen was discussed by Drs. W.G.Powderly and E.G.V. Evans. Mostof the commercialized tests havegood sensitivity and specificity(≥95%), except when they do notrecommend pretreatment of serumwith pronase which decreases theirperformance. Their view was thattiters <1:8 should be interpretedcautiously, especially in patientswithout risk factors. Positive anti-gen detection during routinescreening of asymptomatic patientsat risk for cryptococcosis, such as

Clinicalmanifestations anddiagnosisThree talks were focused on clin-ical manifestations and two on di-agnosis.

Dr. J.E. Bennett first presentedhis experience on hydrocephalusand its management during crypto-coccal meningitis in non-AIDS pa-tients. Although rare (10/153 casesrecorded at the NIH clinical cen-ter), hydrocephalus needs to berecognized in order to prevent de-terioration of mental status. In thecases reported, hydrocephalus wasdiscovered at various times follow-ing the diagnosis of cryptococcosis(simultaneously, to as long as 7years). The major clinical sign pre-sent in all patients was dementia,usually associated with gait ataxia,but other signs such as pa-pilledemia (1/10 patient) and cra-nial nerve palsies (2/10 patients)can be suggestive of hydrocephalus.In all cases, cerebral imaging washelpful and showed bilaterally di-lated cerebral ventricles. Shuntingprovided neurologic recovery in 6,partial improvement in 3 and hadno effect in one patient who hadsuffered several strokes before be-ing shunted. Medical therapy was

chaired by B. Dupont and M.A. Viviani

patients with AIDS, raises the ques-tion whether the patient should beconsidered as being infected or not.Since the natural history of thiscondition has never been studied,the answer cannot be unequivocal.The prognostic value of antigentiter evolution over time has beendiscussed. Several studies have sug-gested that a higher CSF antigentiter at baseline was predictive of apoorer prognosis in patients withAIDS, whereas serum antigen lev-els had no value. In a recent studyby the Mycoses Study Group, aserum antigen titer <1:2048 and aCSF antigen titer <1:512 were pre-

dictive of culture negativity after 2weeks of treatment. CSF monitor-ing of antigen titers seems overallthe best means of checking the effi-cacy of acute therapy or the risk ofrelapse. An important issue in theinterpretation of the results is thehigh variability in titers found for agiven sample when commercialantigen kits and even laboratoriesare changed.

In addition to discussing antigendetection, Dr. Evans comparedAIDS and non-AIDS patients forthe positivity of India ink prepara-tion (≤90% vs. ≤60%) and the posi-tivity of CSF culture (>90% vs. 50-

70%). Antibody detection has nev-er been and will probably never bea means of diagnosing or evenmonitoring cryptococcosis, espe-cially as antigen load prevents thedetection of antibody during infec-tion. Since cryptococcosis is the on-ly opportunistic fungal infection forwhich the diagnosis is straightfor-ward providing that the appropri-ate tests are carried out, very littlehas been made to develop DNA-based detection of Cryptococcus inclinical material.

Bertrand Dupont

Session VIIchaired by

J.E. Bennett and T.R. Kozel

Cryptococcalpolysaccharide

Special report


antibodies specific for differentepitopes of GXM were found todown-regulate, up-regulate, or haveno effect on activation of the alter-native pathway. These results sug-gest that GXM contains unique do-mains which regulate initiationand/or amplification of the comple-ment system. Drs. D.L. Granger,D.M. Call and K.J. Kwon-Chung re-ported studies of the influence ofthe capsule on recognition of C.neoformans by interferon-γ-primedmacrophages. Cells of the acapsularstrain 602 induced nitric oxide syn-thase (NOS) expression by inter-feron-γ-stimulated macrophages. Incontrast, there was little NOS activ-ity by macrophages exposed to en-capsulated wild type strains or tocells of strain 602 that were com-plemented to restore the capsuleformation. These results suggestthat the presence of a capsulemasks the fungus from recognitionby primed macrophages. Drs. Z.M.Dong and J.W. Murphy describedthe effects of glucuronoxyloman-nan, galactoxylomannan andmannoprotein on chemotaxis of

leukocytes. The combined datashowed that cryptococcal polysac-charides, especially GXM, act simi-larly to typical chemoattractantssuch as IL-8. GXM is chemotacticfor human and mouse leukocytes; itinduces L-selectin shedding fromPMN and T lymphocyte surfaces;and it displays both pro-inflamma-tory and anti-inflammatory activi-ties, depending on the distributionof GXM between extravascular andintravascular space, respectively.

Dr. A. Casadevall reported thedevelopment and in vivo activitiesof monoclonal antibodies specificfor GXM, in particular, the ability ofmonoclonal antibodies to providepassive protection in a murine mod-el of cryptococcosis. The protectivecapability of a monoclonal antibodydepended on the fine specificity andisotype of the antibody. These re-sults offer promise for the therapeu-tic potential of passive immuniza-tion and provide direction for vac-cine research aimed at induction ofprotective antibodies.

Thomas R. Kozel

The capsular polysaccharide ofCryptococcus neoformans is an es-sential virulence factor of the yeast.A session entitled “CryptococcalPolysaccharide” explored the struc-ture, genetic regulation and biolog-ical activities of the capsule. Dr. R.Cherniak provided a detailed de-scription of the chemical structureof glucuronoxylomannan (GXM),the major polysaccharide con-stituent of the cryptococcal cap-sule. 13C nuclear magnetic reso-nance spectroscopy for fingerprint-ing GXM structures provided evi-dence that the previously describedsimple structural relationship be-tween polysaccharides of the fourmajor serotypes was an oversimpli-fication in many instances. Indeed,there is considerable variation inmolecular structure of GXM withina given serotype. Drs. Y.C. Changand K.J. Kwon-Chung describedstudies aimed at understanding ge-netic control of capsule formation.Three genes, designated CAP59,CAP60 and CAP64 have been iso-lated which are required for cap-sule formation and virulence. DNAsequence analysis has not providedan indication of the biochemicalfunction for these genes.

Three reports described differ-ent biological activities of the cryp-tococcal capsule. Dr.T.R. Kozel dis-cussed the ability of the capsule toserved as a site for activation of thecomplement cascade and for bind-ing of fragments of C3. Monoclonal

Mycology Courses in Europe (1997)


BELGIUMCourse on Medical and Veterinary Mycology (every year)

Organizers: Proff. D. Swinne and Ch. De Vroey(lectures/aerobiology: Drs. N. Nolard, M. Detandt)Address: Institute of Tropical Medicine,Nationalestr. 155,B-2000 Antwerpen, Fax +32 3 2161431Duration-date: 5 months (one full day/week) - February to JuneHours theory/practice: Theory 30h / practice 70hAdmitted participants: 20 Certificate: Diploma

FRANCECours de Mycologie Médicale (every year)

Organizer: Dr. C. de BievreAddress: Institut Pasteur, 28 Rue du Dr. Roux,75015 Paris,Fax +33 1 45688420Duration-date: 8 weeks - 28 April-20 June 1997Hours theory/practice: Theory 100h / practice 100hAdmitted participants: 20Certificate: Diploma

Diplôme universitaire sur les mycoses systémiques(every year)

Organizers: Prof. B. Dupont, Dr. F. DromerAddress: Institut Pasteur or Fac. Médecine Necker - EnfantsMalades, 28 Rue du Dr. Roux, F-75724 Paris, Fax +33 1 45688218Duration - date: 10 week (3h each week)-Mars to MayHours theory/practice: Only theoryAdmitted participants: 20 to 30Certificate: Diploma

GERMANYCourse on Clinical Mycology(every year)

Organizer: Dr. K. Tintelnot, Robert-Koch-Institut,Bundesgesundheitsamt, Nordufer 20, D-13353 BerlinAddress: Working Group “Clinical Mycology” of DMykGDuration - date: 2 days - 21-22 February 1997Admitted participants: 25

Course on Experimental Mycology(every year)Organizer: Dr. H.-J. Tietz, Zahnarzt, Facharzt für Mikrobiologie,Hautklinik der Charité, Schumannstr. 20/21, D-10117 BerlinAddress: Working Group “Mycological Laboratory Diagnostics”of DMykGDuration: 2 daysAdmitted participants: 30

POLANDCourse on Dermatological Mycology

Organizer: Prof. R. Maleszka and othersAddress: Oddzial Dermatologiczny, 60-5 Poznan, ul. Dojazd 37Duration - date: 5 days - September, 1997Hours theory/practice: Theory 12h / practice 36hCertificate: Diploma

Advances in Mycologic DermatologyOrganizer: Prof. Dr. hab. E. Baran and othersAddress: Clinic of dermatology, 50-368 Wroclaw,Chalubinskiego 1Date: 2 April, 1997Admitted participants: 10Certificate: Diploma

PORTUGALCourse on Medical Mycology (every year)

Organizers: Drs. M. Rocha, R. Velho, L. Rosada, J. Brandão,I. CostaAddress: ASPOMM, Centro de Dermatologia, R. José Estêvão135, 1150 Lisboa, Fax +351 1 3522359Duration - date: 3 weeks - 1-18 April, 1997Hours theory/practice: Theory 35h / practice 40hAdmitted participants: 10Certificate: Diploma

SPAINCourse on Medical Mycology (every year)

Organizer: Dr. Josep M. Torres-Rodriguez, Unitat de Microbiologia,Institut Municipal D’Investigació Mèdica, c/ Aiguader 80, E-08003Barcelona, Fax +34 3 221 3237Address: Departamento de Microbiologia, Fac. Medicina“UDIMAS”, Universidad Autonoma de BarcelonaDuration: 3 weeksHours theory/practice: Theory 65% / practice 35%Admitted participants: 15Certificate: Diploma

SWEDENCourse on Medical Mycology

Organizers: Drs. L. Edebo, J. FaergemannAddress: Sahlgrenska University Hospital, Dept. of ClinicalBacteriology, Guldhedsgatan 10, S-413 46 GöteborgFax +46 31 604975Duration: 2 daysAdmitted participants: 12Certificate: Diploma

THE NETHERLANDCourse on Medical Mycology (Dutch language edition)

Organizer: Centraalbureau voor Schimmelcultures, BaarnAddress: CBS, Oosterstr. 1, Baarn, Fax +31 3554 16142Duration - date: 3 weeks - 1-19 April 1997Admitted participants: 25Certificate: DiplomaNB. A German language edition of this course for 60 participants willbe held in Berlin, 3-15 March 1997

Course on Superficial Mycoses,for dermatologists

Organizer: Centraalbureau voor Schimmelcultures, BaarnAddress: CBS, Oosterstr. 1, Baarn, Fax +31 3554 16142Duration: 2 daysHours theory/practice: Theory 35% / practice 65%Admitted participants: 25Certificate: DiplomaNB. Several editions, either in Dutch or in English language, in TheNetherlands and other countries

Course on General Mycology(English language edition)

Organizer: Centraalbureau voor Schimmelcultures, Oosterstr. 1,Baarn, Fax +31 3554 16142Address: CBS, and BioCentrum, Kruislaan 318, AmsterdamDuration - date: 3 weeks - 24 February-13 March 1997Admitted participants: 25Certificate: Diploma

UNITED KINGDOMBSMM Course on Diagnostic Medical Mycology

Organizers: Prof. E.G.V. Evans, Prof. R.J. Hay, and Drs. G. Midgley,L.J.R. Milne, M.D. Richardson, D.T. Roberts, D.W. Warnock andothersAddress: c/o Prof. E.G.V. Evans, Dept. of Microbiology, University ofLeeds, UK-Leeds LS2 9JT, Fax +44 113 2335640Duration - date: 1 week - 7-11 April 1997Hours theory/practice: Theory 15h / practice 18hAdmitted participants: 55

Master of Science in Medical Mycology(every year)

Organizers: Prof. E.G.V. Evans, and Drs. R. Barton, D.J. Adams,H.R. Ashbee and othersAddress: c/o Dr. H.R. Ashbee, Dept. of Microbiology,University of Leeds, UK-Leeds LS2 9JT, Fax +44 113 2335640Duration: 1 yearHours theory/practice: Theory approx. 150h /practice approx. 400hAdmitted participants: 20Certificate: MSc, University of Leeds

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