Hellenic Center for Disease Control and PreventionAgrafon 3- 5, Maroussi, 15123, Tel: +30 210 5212000,info@keelpno.gr, http://www.keelpno.gr

February 2013 ISSN 1792-9016Vol. 24/ Year 2nd

MINISTRY OF HEALTH

HCDCP

HELLENIC CENTER FORDISEASE CONTROL & PREVENTION

MINISTRY OF HEALTH

Highlights

Read about the international distinc-tions of Mrs Konstantina Politis, a scientific consultant for HCDCP and head of the Hellenic Center for Co-or-dinating Hemovigilance (SKAE). She has been honored for her outstand-ing and sustained commitment in the area of hemovigilance, the safety and quality of blood.

More on page 33

Main article: HCDCP’s

proposal for infection

surveillance systems among

transplant patients 2

Surveillance data 7

Invited articles 10

HCDCP’ s departments activities 23

Recent publications 24

Future conferences 32

Outbreaks around the world 28

Interview 34

Myths and truths 31

News from the HCDCP’s administration 33

Quiz of the month 34

Contents:

The Hellenic Center for Disease Control and Prevention (HCDCP)’s proposal for the creation of an in-fection surveillance network in the context of transplantation is presented as the main article of this issue.

More on page 2

Information about measures for the prevention and treatment of fungal infections can be found in this issue.

More on page 8

Fungal infectionsDuring the past 2 decades, there have been significant changes in the frequency, causes and pathogenicity of fungal infections. Although it is thought that there are almost 1.5 million known and unknown fungal species on earth, only 300,000 have been described, of which only 600 have been identified as opportunistic pathogens, and less than 100 as common pathogens (causing infections of mucous, soft tissues, skin, nails and hair, and other diseases such as allergies and lethal invasive infections).

Until 1960, severe, systematic mycoses were sporadic or rarely identified as a post-mortem finding. But there has been a dramatic increase in fungal cases (500%) during the last 20-30 years. The (annual) incidence of all fungal infections is estimated to be near 178/1,000,000 head of population, and, according to a large American study, the rates of systemic mycosis in hospital patients has risen from 2/1,000 in 1980 to 3.8/1,000 in 1990.

Fungi are the fifth most common cause of nosocomial infection in intensive care units (ICUs), according to the results of a pan-European study (an EPIC study in 1995). Moreover, they are the seventh most common cause of infection-related deaths. Seventy per cent of these cases were caused by Candida spp., Aspergillus spp. and Cryptococcus neoformans. Candida spp. were the sixth most common cause of nosocomial infection and the fourth most commonly isolated from blood pathogens, according to another large study (CDC in 1992).

Mycoses have been at the center of medical interest lately, because of their increased frequency among oncology, transplantation and AIDS patients, and among immune-compromised patients in general. This increased frequency has been attributed mainly to the increased number of hospital patients with predisposing factors for the development of systematic mycoses. Although the actual mortality rates are unknown because of the lack of any epidemiological data, the incidence of systematic mycoses is increasing because of current, modern medical practices.

Invasive fungal infections still remain under-studied and under-diagnosed compared with other infectious diseases, despite their high mortality rates. Even some international, highly influential, health organizations, such as the World Health Organization (WHO) and the Bill & Melinda Gates Foundation, seem to under-estimate the world’s burden of disease caused by fungal infections.

What can be done to ‘correct’ this situation and solve the problem?

The most significant, positive, intervention that can be made is to increase awareness of this issue. That is the target of this e-bulletin of the Hellenic Center for Disease Control and Prevention (HCDCP).

Professor George Petrikkos

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Main article Main article

HCDCP’s proposal for infection surveillance systems among transplant patients

Transplantations are one of the biggest medical achievements of the 20th century and nowadays constitute an established therapeutic practice that can prolong and improve the quality of life for many people. One of the essential conditions for the application of transplantations is public awareness and acceptance of the idea of organ donation. In our country, according to the latest records of the National Organization for Transplantations, in the past 11 years (2001–2011) 2,511 transplantations of solid organs from cadavers and compact living donors and at least 440 bone marrow transplantations from non-relative volunteer donors have been conducted. Unfortunately, according to the latest data from the European Transplant Co-ordinating Body, Greece holds one of the lowest places in terms of numbers of transplantations, especially of cadaver donors, with organ donations for 2011 just 6.9 per million population.

Infections are one of the main causes of morbidity and mortality among transplant recipients. The diagnosis, treatment and control of infectious diseases during the pre- and post-transplantation period represent parameters that are directly linked to the success of the transplantation and the survival rate of recipients. More than 50% of transplant recipients develop an active infection after transplantation, with direct and indirect effects arising from the infection, such as immunosuppression, opportunistic infections, the risk of graft rejection and their contribution to the emergence of malignancies. Factors that determine the risk of infection during transplantation include the level of exposure to infectious agents and the immunosuppression of transplanted individuals. Infections among transplanted patients constitute a challenge for clinicians because they refer to a great variety of micro-organisms, the route of these infections is fast with a heavy burden, and they are often characterized by serious and non-specific signs.

Surveillance of infections in the context of transplantation is necessary given that clinicians often encounter complications during the treatment of related infections. This is because of the expanded spectrum of pathogenic agents, the often atypical clinical and radiologic presentations, the fact that therapeutic interactions can be observed, and the fact that the situation can be confounded by graft rejection or graft versus host disease (GVHD); and all of the above are further exacerbated by the existence of new pathogens, increasing antimicrobial resistance and limited therapeutic options for viral infections.

Many countries, including Spain, Germany and the USA, currently operate organized infection surveillance systems among transplant patients.

The Hellenic Center for Disease Control and Prevention (HCDCP) has proposed the development and operation of an infection surveillance network for solid organ and bone marrow transplantation, in collaboration with the National Organization for Transplantations and major transplantation centers in Greece for bone marrow, heart, kidneys and liver.

The network’s objectives for tackling infections in transplanted patients are as follows.

• Systematic surveillance and acknowledgement of the extent of the problem, with the compulsory declaration of all infections in transplanted patients, with the long-term objective of establishing strong foundations for the development of a national network.

• Determining the epidemiology of infections of transplanted patients (frequency, type of infection and pathogen, be it bacteria, fungi, viruses or protozoa, resistance, treatment and outcome).

• Monitoring temporal trends by calculating the incidence per transplantation center.• Monitoring the impact of antimicrobial resistance.• Identifying risk factors for the occurrence of infections after transplantation.• Developing strategies based on the results of surveillance, which will contribute to reducing

infections in transplanted patients.• Promoting the implementation of measures to control infections in transplantation units,

with the implementation of guidelines and mechanisms for geographic isolation through

education of the HCWs, implementation of infection control programs for achieving zero tolerance, and finally monitoring compliance of the above infection-control programs.

The methodology by which it might be possible to create the above network is the creation of a system of active surveillance of infections in patients who undergo a transplantation in which infections from germs, viruses, fungi and protozoa will be recorded, definitions for each category of infection will be developed according to international guidelines, a ‘registration card’ will be formulated and an ‘electronic database’ created for the safe-keeping of data, statistical analyses and monitoring the evaluation of the data.

These actions will involve all stakeholders, such as the National Organization for Transplantations, the health districts across the country and the transplantation centers. They also concern the HCDCP, which will be responsible for issuing guidelines in collaboration with the transplantation centers and the relevant scientific societies, for the surveillance of infections in transplanted patients, monitoring the implementation of the infection control measures, and follow-up of interventions in the case of outbreaks of newly arising pathogenic micro-organisms or resistance mechanisms, as well as for organizing educational meetings with the transplantation centers responsible and the National Organization for Transplantations, and writing and sending out reports on a biannual basis.

The co-ordination and scientific support of this network will include the establishment of a working group for the co-ordination of the network operation and application of the results of the surveillance, as well as for the proper implementation of the control measures and the prevention of infections. The scientific team will be composed of members of the network of transplantation centers and representatives from relevant scientific societies.

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Promoting the necessity and importance of organ donation and the development of transplantations in Greece makes the obligation of public health bodies to organize a network for surveillance and infection control obvious, because the latter are such an important factor in the morbidity and mortality of transplanted patients and jeopardize the outcome of the transplantations.

L. Ftika, Office of Nosocomial Infections, Antimicrobial Resistance and Rational Use of Antibiotics

H. C. Maltezou, Department of Interventions in Health-Care Facilities

Main article Surveillance data

Table 1: Number of notified cases in January 2013, and median, maximum and minimum numbers of notified cases in January for the years 2004−201e, Mandatory Notification System, Greec

Disease Number of notified casesJanuary 2013

Median number January

2004−2012

Minimum number January

2004-2012

Maximum number January

2004-2012Botulism 0 0 0 0

Chickenpox with complications 0 1 0 7

Anthrax 0 0 0 0

Brucellosis 8 6 1 30

Diphtheria 0 0 0 0

Arbo-viral infections 0 0 0 0

Malaria 3 2 0 10

Rubella 0 0 0 0

Smallpox 0 0 0 0

Echinococcosis 0 1 0 4

Hepatitis Α 20 10 1 25

Hepatitis B, acute and HBsAg(+) in infants

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Surveillance data Surveillance data

Table 2: Number of notified cases by place of residence (region), January 2013, Mandatory Notification System, Greece (place of residence is defined according to the home address of the patient)

Disease Number of notified cases

Region

Eas

tern

Mac

edonia

an

d T

hra

ce

Cen

tral

Mac

edonia

Wes

tern

Mac

edonia

Epirus

Thes

salia

Ionia

n isl

ands

Wes

tern

Gre

ece

Ste

rea

Gre

ece

Att

ica

Pelo

ponnes

e

Nort

her

n A

gea

n

South

ern A

egea

n

Cre

te

Unkn

ow

n

Brucellosis 0 0 0 0 3 0 2 0 1 1 0 0 0 1

Malaria 0 0 0 0 0 0 0 0 2 1 0 0 0 0

Hepatitis A 0 4 0 2 4 0 0 0 1 9 0 0 0 0

Hepatitis B, acute and HBsAg(+) in infants

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Invited articles Invited articles

Measures for preventing and confronting fungal infections

We need to focus our attention on four important issues.

First: good, effective, fast, simple and cheap diagnostic access is absolutely necessary, in order to apply timely antifungal treatment.

Most of the diagnostic techniques have a delay before the results are available, and are characterized by low specificity or/and sensitivity. The problems of the diagnostic methods combined with the often latent and insidious clinical situation results in diagnostic failure or a late diagnosis of fungal infection and therefore subsequent insufficient clinical treatment. Applying the right diagnostic techniques would have an important impact on mortality and would decrease the morbidity caused by fungal infections.

Second: safer and more effective antifungal drugs are absolutely necessary.

Despite the fact that there are several categories of antifungals on the market, their use has not been successful in all cases. In fact there has only been moderate success in confronting the high mortality rates caused by invasive mycoses such as candidiasis, aspergillosis and cryptococcosis. However, it should be noted that this partial failure is also because of the delays in diagnosis and identification of the fungi. In addition, antifungal drugs are restricted regarding the route of administration, their toxicity, their narrow spectrum of action, the adverse events they cause, the development of resistance against them and, finally, their bioavailability in the targeted tissues. The afore-mentioned factors plus the high cost of many antifungal therapies aggravate the problem, especially in environments with poor resources, where consequently mortality is much higher.

Although modern therapeutic schemes may prove to be more efficient than the older drugs, it is necessary that new, cheaper drugs, with, most importantly, faster antifungal action should be marketed in order to overcome the previously described problems. But at the moment only a few antifungals are currently under development and it could be many years before they are available for clinical practice (if at all). Thus we must highlight the need for a better understanding of which patients are in the greatest danger of suffering fungal infections, in order to use targeted preventive measures for their protection.

Third: vaccines should be developed for clinical use.

Currently there are no approved human vaccines against any pathogenic fungus, despite progress in understanding the specific antifungal immune response. Effective vaccines have been tested on experimental animals, but very few have reached later clinical trial phases. Additionally, for the prevention of an invasive infection, we should note that an effective vaccine could benefit patients suffering from fungal allergies and patients with mucosal and skin infections such as vulvovaginal candidiasis.

Finally: it is necessary to have accurate data on the burden of fungal diseases and on the economic cost that these mycoses cause, in order to raise scientific interest and investments on this medical field, at a global level.

The major funding organizations of the USA and the United Kingdom are currently investing only 2% of their infectious disease-specific budget on research of fungal infections. Private funding could be raised through the development of collaboration between academic institutions and public health bodies. The population that is in danger of life-threatening fungal infections is growing globally and tackling the challenges of these pathogens should now be of high priority.

George Petrikkos, Professor of Internal Medicine-Infectious Diseases,Philip Koukouritakis, Head of the HCDCP’s E-health Information Office

Emerging mycoses

Introduction

Invasive fungal infections (IFIs) are life-threatening opportunistic infections. They occur primarily in immunocompromised hosts, such as patients with hematological malignancies, patients with solid organ or stem cell transplants, patients with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) and patients with diabetes, as well as in critically ill patients. The newer drugs and more aggressive therapies that have been introduced in recent years have led to a higher survival rate for these patients, which has also led to a prolonged immune suppression. As a consequence, the probability of acquiring IFIs has increased. Also, selective pressure as a result of antifungal prophylactic strategies have led to epidemiological changes, with the emergence of more resistant strains and new opportunists (Table 1).

The fungi concerned exist in the environment and rarely affect immunocompetent individuals. In the immunocompromised individual, however, they can grow rapidly and cause considerable morbidity and mortality. Their geographic distribution varies and their clinical spectrum is vast, depending on the immunological situation and the underlying disease. A prompt and accurate diagnosis is crucial for a better outcome; therefore a high degree of suspicion is needed, based on the knowledge of risk factors, disease manifestations and local epidemiology.

Infections as a result of resistant Candida and Aspergillus species

Candida spp. and Aspergillus spp. remain the most common fungal pathogens, but species resistant to antifungals used for empirical treatment are on the rise. Candida glabrata and C. parapsilosis usually yield high MIC values for azoles or echinocandins, respectively. Their distribution displays notable geographical differences, with C. glabrata being the second most frequent in Switzerland, the United Kingdom and the USA, and C. parapsilosis the third most frequent, whereas the opposite is true for south-European countries. Candida tropicalis and other rare species are isolated more frequently from patients with hematological malignancies.

Aspergillus fumigatus is the causative agent of >90% of invasive aspergillosis cases, with good sensitivity to the newer azoles, especially to voriconazole, which is the drug of choice. There is some concern, however, that resistance to all azoles is emerging, after the isolation of resistant strains from clinical cases in England and the Netherlands. This could be because of selection pressure after high-dose azole exposure in hospitals, but evidence is accumulating that resistance is mainly the result of the overuse of agricultural azoles. Sporadic cases have been identified in other parts of Europe. Cases with A. terreus, a species resistant to amphotericin B, are also emerging.

Infections as a result of Cryptococcus gattii

Cryptococcus neoformans and C. gattii are the major cryptococcal pathogens. Cryptococcus neoformans affects immunocompromised individuals, mainly HIV patients, but C. gattii also affects immunocompetent patients. Cryptococcus gattii has gained interest recently, because since 1999 there has been an outbreak in eastern Vancouver Island, an area not generally thought to be endemic for this organism. Cases have since been described in the Pacific North-west, in both Canada and the USA. This species was considered to be endemic in tropical and subtropical areas, but environmental strains have also been identified in Europe. Human patient isolates from Mediterranean Europe are clustered into a distinct genotype, with animal and environmental isolates.

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Invited articles Invited articles

Infections as a result of rare yeasts

Rare yeast genera, such as Trichosporon, Pichia, Rhodotorula and Malassezia, and the species Geotrichum capitatum and Saccharomyces cereviciae, cause Candida-like infections, usually catheter-related in immunocompromised hosts.

Mucormycosis (zygomycosis)

Mucormycosis (zygomycosis, formerly phycomycosis) has emerged as the third most common invasive mycosis after candidiasis and aspergillosis in patients with hematological malignancies and allogeneic stem cell transplantation. Mucormycosis also remains a threat in patients in the western world with diabetes mellitus. In recently developed countries, such as India, it affects mainly patients with uncontrolled diabetes or trauma. Epidemiological data on this type of mycosis are scant. The estimated incidence in the USA is 1.7 cases per million population per year. Based on anatomical localization, mucormycosis can be classified as one of six forms: (1) rhinocerebral, (2) pulmonary, (3) cutaneous, (4) gastrointestinal, (5) disseminated and (6) uncommon. The underlying conditions can influence clinical presentation and outcome, with a mortality rate of 40–80%. Predisposing factors are presented in Table 2. Genera affecting humans are: Rhizopus (the most frequent), Mucor, Lichtheimia (formerly Absidia and Mycocladus), Apohysomyces, Cunninghamella, Saksenaea and Rhizomucor.

Fusariosis

Fusarium is a plant and animal pathogen ubiquitous in nature. More than 50 species have been described, but only a few affect humans: F. solani (50% of cases), F. oxysporum, F. proliferatum and F. verticillioides (F. moniliforme). Patient groups at risk and predisposing factors are presented in Table 3. The incidence is higher in patients with acute myelogenous leukemia (AML). The mortality of invasive fusariosis is very high (36–100%), depending on the site of infection and immune status. In immunocompetent patients, Fusarium causes mainly keratitis and onychomycosis.

Scedosporiosis and other hyalo- and phaeohyphomycoses

Species of Scedosporium and Pseudoallescheria boydii cause a vast spectrum of infections depending on immune status and mode of acquisition (skin trauma or inhalation). In severely immunocompromised patients, they can cause a rapidly progressive sinopulmonary, sino-orbital or disseminated infection. Mortality is high because of the resistance to antifungals. Scedosporium prolificans (S. inflatum) is particularly resistant. Scedosporium apiospermum causes mycetoma in immunocompetent patients, and pneumonia, brain abscesses and disseminated infection in victims of near drowning.

The spectrum of diseases caused by dematiaceous (melanized) fungi (phaeohyphomycoses) includes allergic disease, superficial and deep local infections, pneumonia, brain abscesses and disseminated infection (Table 1).

Concluding remarks

In order to broaden our knowledge of the epidemiology, diagnostic procedures and clinical course of invasive fungal infections caused by unusual invasive fungi, international collaboration is very important. The working group (WG) on zygomycosis, initially formed under the auspices of ECMM, has now expanded and includes participants from all around the world as an ECMM/ISHAM WG. For fusariosis there is an ECMM multicenter survey. A global registry of other rare mold infections is co-ordinated by Fungiscope*.

*International collaborations for registering rare mold infections:

Zygomycosis registry

www.zygomyco.net

WG co-ordinator: G. Petrikkos, MD, PhD, Professor of Medicine and Infectious Diseases, 4th Medical Department, National Kapodistrian University of Athens, ‘ATTIKON’ Hospital

National co-ordinator for Greece: A. Skiada, MD, 1st Department of Propaedeutic Medicine, National Kapodistrian University of Athens, ‘LAIKON’ Hospital

Fusariosis survey

WG co-ordinator: Anna Maria Tortorano, MD, PhD, Professor of Medical Microbiology, Università degli Studi di Milano

National co-ordinator for Greece: M. Drogari-Apiranthitou, MD, PhD, Clinical Microbiologist, Infectious Diseases Research Laboratory, 4th Medical Department, National Kapodistrian University of Athens, ‘ATTIKON’ Hospital

Global registry of other rare mold infections

Fungiscope: www.fungiscope.net

Chair: Oliver A. Cornely, MD, FIDSA, Cologne

Table 1: Emerging fungi and clinical characteristics

Organisms Risk factors Clinical manifestations

Yeasts Candida

C. parapsilosisC. glabrataC. tropicalisC. krusei

CVC, dialysis, neutropenia, steroids, colonization, antimicrobials, surgery

Non-specific, sepsis not responding to antimicrobials, endophthalmitis

CryptococcusC. neoformansC. gattii

AIDS, T-cell immunodeficiencies SteroidsTrauma and unknown risk factors in immunocompetent patients (C. gattii)

Meningoencephalitis, pneumonia, skin infection, fever of unknown origin

Other yeasts

RhodotorulaTrichosporonPichia anomalaMalassezia

Cancer, neutropenia, steroids, CVC, parenteral nutrition

Disseminated infection, as in Candidiasis

Molds Aspergillus

A. flavusA. terreusA. niger

Prolonged neutropenia, lung transplantation, HSCT, HIV, steroids

Initially as pneumonia or sinusitis. Dissemination to CNS. Possibly mild symptoms

MucoralesRhizopus Mucor Lichtheimia (Absidia)

Hematological malignancy, neutropenia, immune deficiency, deferoxamine, diabetes/ketoacidosis

Mucormycosis (zygomycosis): rhino-orbito-cerebral, cutaneous, pulmonary, disseminated, gastrointestinal, other organs

Fusarium

F. solaniF. verticillioides (F. moniliforme)F. oxysporum

Trauma, contact lenses, onychomycosis, neutropenia

Skin, lung, sinuses involvement in disseminated infection

ScedosporiumS. apiospermum/ Pseudallescheria boydii S. prolificans

Prolonged neutropenia, surgery, trauma, near-drowning

Fever not responding to antimicrobials, mycetoma, CNS dissemination

Other molds Hyalohyphomycetes Phaeohyphomycetes

PaecilomycesAcremoniumTrichodermaAlternaria, Curvularia, Bipolaris, Exophiala*Cladophialophora bantiana,*

HSCT, immunodeficiency, neutropenia, CVC, infected medical equipment, peritoneal dialysis

Ocular infections (Paecilomyces, Acremonium), mycetoma (Acremonium), peritonitis in dialysis patients, pneumonia, sepsis, CNS infection

*In the tropics, seldom in Europe.

CVC, central venous catheter; HSCT, hematopoietic stem cell transplantation; CNS, central nervous system.

http://www.zygomyco.nethttp://www.fungiscope.net

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Table 2: Risk groups and clinical forms of mucormycosis

Condition Clinical forms

Hematological malignancy/HSCT Pulmonary, sinusitis, cutaneous, rhino-orbital

Diabetes mellitus/ketoacidosis Rhinocerebral, pulmonary, rhino-orbital cutaneous

Corticosteroids/autoimmune diseases Disseminated, renal, cutaneous, rhino-orbital gastrointestinal

Solid organ transplantation/GVHD Pulmonary, sinusitis, cutaneous, rhino-orbital, disseminated

HIV infection/IV drugs Cerebral, cutaneous, renal, heart, rhinocerebral, disseminated

Iron overload Fe/Al chelators (deferoxamine)

Disseminated pulmonary, rhinocerebral, cerebral, cutaneous, gastrointestinal

Burn/trauma/surgery/insect bite Cutaneous, pulmonary, sino-orbital, rhinocerebral, gastrointestinal.

Antifungal therapy (VOR, ITZ, CAS/echinocandins) Sinopulmonary

Neonatal prematurity/malnutrition Broad-spectrum antimicrobial agents

Cutaneous, gastrointestinal, pulmonary, sino-orbital, rhinocerebral

HSCT, hematopoietic stem cell transplantation; GVHD, graft versus host disease; IV, intravenous; VOR, voriconazole; ITZ, itraconazole; CAS, caspofungin.

Table 3: Risk factors for fusariosis

Immunodeficient Immunocompetent

Hematological malignancies

Severe prolonged neutropenia

(>90% of cases)

T-cell immunodeficiencies

HSCT/GVHD

Prolonged steroid therapy

Foreign bodies:

• contact lenses

• portable peritoneal dialysis

• CVC

Trauma, burns

HSCT, hematopoietic stem cell transplantation; GVHD, graft versus host disease; CVC, central venous catheter.

References:

1. Binder U, Lass-Flörl C. Epidemiology of invasive fungal infections in the Mediterranean area. Mediterr J Hematol Infect Dis 2011;3:e20110016.

2. Verweij PE, Kema GH, Zwaan B, Melchers WJ. Triazole fungicides and the selection of resistance to medical triazoles in the opportunistic mould Aspergillus fumigatus. Pest Manag Sci 2013;69:165-170.

3. Skiada A, Pagano L, Groll A, et al., for the European Confederation of Medical Mycology Working Group on Zygomycosis. Zygomycosis in Europe: analysis of 230 cases accrued by the registry of the European Confederation of Medical Mycology (ECMM) Working Group on Zygomycosis between 2005 and 2007. Clin Microbiol Infect 2011;doi 10.1111/j.1469-0691.2010.03456.x

4. Petrikkos G, Drogari-Apiranthitou M. Zygomycosis in Immunocompromised non-haematological patients. Mediterr J Hematol Infect Dis 2011;3:e2011012.

5. Richardson M. The ecology of the Zygomycetes and its impact on environmental exposure. Clin

Microbiol Infect 2009;15(Suppl 5):2-9.

6. Nucci M, Anaissie E. Fusarium infections in immunocompromised patients. Clin Microbiol Rev 2007;20:695-704.

7. Groll AH, Walsh TJ. Uncommon opportunistic fungi: new nosocomial threats. Clin Microbiol Infect 2001;7(Suppl 2):8-24.

8. Malani AN, Kauffman CA. Changing epidemiology of rare mould infections: implications for therapy. Drugs 2007;67:1803-1812.

M. Drogari-Apiranthitou, MD, PhD, Clinical microbiologist, Infectious Diseases Research Laboratory, 4th Medical Department, National Kapodistrian University of Athens,

‘ATTIKON’ Hospital

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Fungal infections in hematological and transplant patients

Invasive fungal infections (IFIs) in hematological and transplant patients have been associated with significant morbidity and mortality [1-4].

Several risk factors predispose to IFIs, such as prior use of corticosteroids, intensive chemotherapy, the presence of indwelling central catheters, tissue damage, and advanced underlying disease, along with a severe [absolute neutrophil count (ANC) ≤500 cells/µL or even ≤100 cells/µL] and protracted (>7-10 days) neutropenia [3,4].

Epidemiology

Over the last decade, changes in the epidemiology of IFIs have been observed. Although Candida, Aspergillus and Cryptococcus spp. are the more frequently isolated pathogens, other rare fungi, such as Mucor, Fusarium and Scedosporium spp., hyalohyphomycetes and

pheohyphomycetes, have emerged [1-4].IFIs are more frequent in patients with hematological malignancies with severe and protracted neutropenia than in those with solid tumors. In an autopsy study, IFIs have been identified in 25% of patients with leukemia, 12% of those with lymphoma and 5% of those with solid tumors. Candidiasis was the most common. Candida was isolated in 58%, and Aspergillus in 30%, of these patients [5]. However, recently an increasing frequency of mold infections has been observed, while cases of candidiasis are decreasing [1-4].

The overall incidence of IFIs in hematopoietic stem cell transplant (HSCT) recipients is about 3.4%, with aspergillosis being the most common (43%), followed by candidiasis (28%), fusariosis (16%), scedosporiosis (16%) and zygomycosis (8%), while pneumocystosis and cryptococcosis are rarely seen [1,6].

Finally, among solid organ transplant (SOT) recipients, candidiasis is more common than aspergillosis, except for lung recipients, in whom aspergillosis is more frequent [1].

Pathogens: clinical features

Aspergillus fumigatus remains the most frequently isolated mold. Other species, such as A. flavus, A. terreus, and A. niger, are less frequently implicated. Aspergillus terreus is associated with amphotericin B resistance and a high mortality. Pulmonary aspergillosis with subsequent dissemination is the most common clinical presentation. Patients present with fever, cough, hemoptysis, dyspnea, pleuritic chest pain, respiratory failure and altered mental status. In the immunocompromised patient, early in the course of infection, symptoms and clinical signs may not be specific, and can be subtle or absent [1,3,4], while the distinction between colonization and infection is difficult. Isolation of the pathogen from the lower respiratory tract in lung transplant recipients is usually by colonization; patients with hematological malignancies or HSCT have a high positive predictive value for invasive disease [1,2,7].

Over the last few years an increasing number of IFIs as a result of hyalohyphomycetes, including, Acremonium, Fusarium, Paecilomyces and Scedosporium spp., has been observed [1,2].

Candida infections are decreasing. Although C. albicans remains the species most frequently isolated, non-albicans spp. are increasingly seen. This shift is partly because of the routine use of azole prophylaxis in high-risk patients [1,2].

Candida causes a wide spectrum of diseases, including candidemia, peritonitis, endopthalmitis, esophagitis and urinary tract infections. Clinical signs may be fever, fatigue and leukocytosis [1,2].

Mucormycosis has been associated with significant mortality (6-80%). In a mucormycosis review, 7% of cases occurred in SOT and 5% in bone marrow transplant recipients. Among the HSCT recipients, 50% had pulmonary disease and 16% sinusitis [1,2].

The risk of Pneumocystis jiroveci infection in HSCT and SOT recipients without prophylaxis is estimated to be 5-15%. However, after routine prophylaxis with trimethoprim-sulfamethoxazole the occurrence is extremely rare [1]. In a review of kidney recipients, the cumulative incidence of P. jiroveci pneumonia was 0.4%. Patients receiving serolimus were at increased risk [1,2].

Finally, the incidence of invasive cryptococcosis in non-human immunodeficiency virus (HIV)-infected patients has been found to be 18% in SOT recipients, 9% in patients with hematological malignancies, 9% in patients with other malignancies and less than 1% in HSCT recipients [1,2]. Cryptococcosis most commonly involves the lungs and central nervous system, but cutaneous infection and disseminated disease may also occur [1].

Timing of IFIs

The time taken for IFIs to develop in patients with hematological malignancies and febrile neutropenia is different for candidasis, which occurs during the second and third weeks of neutropenia, and aspergillosis, which occurs after the third week [3,4].

IFIs following HSCT happen during three time periods: an early period (≤40 days), during which candidiasis is common, a late period (41-180 days post-HSCT) and a very late period (>180 days post-HSCT), during which invasive aspergillosis occurs more frequently. Aspergillosis occurs more frequently later after allogeneic HSCT compared with autologous HSCT. Mucormycosis occurs more than 90 days after transplantation, while scedosporiosis occurs within the first 30 days post-transplant [1,6].

IFIs following SOT also happen during three time periods. Candidiasis occurs in all three periods, aspergillosis within the first year (usually >90 days) and cryptococcosis during the third period, most commonly after the first year post-transplantation [1,2].

Diagnosis

The diagnosis of IFIs is difficult because of the lack of specific signs and symptoms until late in the disease process, and the difficulty in obtaining infected tissue, which is required for specific diagnosis. Imaging may help provide a strong indication. However, new diagnostics tools, such as galactomannan (Αspergillus spp.), β-glucan assays (Αspergillus spp., Candida spp. and P. jiroveci) and polymerase chain reaction (Αspergillus spp.), offer opportunities for early diagnosis and appropriate treatment [3,4].

Treatment

Currently, despite the increased number of new, more effective and safer antifungal drugs, the treatment of IFIs is frequently suboptimal, with very high mortality rates (>50%) depending on the pathogen and the disease [1]. Effective management depends on early detection of the responsible pathogen.

For empirical antifungal treatment, the lipid formulations of amphotericin B, echinocandins (caspofungin, micafungin and anidulafungin) and voriconazole can be considered [1,3,4].

Finally, the role of prophylaxis in allogeneic HSCT recipients or those undergoing intensive remission-induction or salvage induction chemotherapy for acute leukemia is well established [1,3,4]. The prophylactic administration of fluconazole, posaconazole and micafungin has reduced the incidence of IFIs and in some cases the attributable mortality [3,4].

References:

1. Person AK, Kontoyiannis DP, Alexander BD. Fungal infections in transplant and oncology patients. Hematol Oncol Clin North Am 2011;25:193-213.

2. Pappas PG, Alexander BD, Andes DR, et al. Invasive fungal infections among organ transplant

http://www.ncbi.nlm.nih.gov/pubmed/21236398http://www.ncbi.nlm.nih.gov/pubmed?term=Pappas PG%5BAuthor%5D&cauthor=true&cauthor_uid=20218876http://www.ncbi.nlm.nih.gov/pubmed?term=Alexander BD%5BAuthor%5D&cauthor=true&cauthor_uid=20218876http://www.ncbi.nlm.nih.gov/pubmed?term=Andes DR%5BAuthor%5D&cauthor=true&cauthor_uid=20218876

16 17

Invited articles Invited articles

recipients: results of the Transplant-Associated Infection Surveillance Network (TRANSNET). Clin Infect Dis 2010;50:1101-1111.

3. Freifeld AG, Bow EJ, Sepkowitz KA, et al. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the Infectious Diseases Society of America. Clin Infect Dis 2011;52:e56-e93.

4. National Comprehensive Cancer Network (NCCN). Prevention and Treatment of Cancer-Related Infections. NCCN Guidelines in Oncology. Available at www.nccn.org [accessed 4 February 2011].

5. Bodey G, Bueltmann B, Duguid W, et al. Fungal infections in cancer patients: an international autopsy survey. Eur J Clin Microbiol Infect Dis 1992;11:99-109.

6. Young J-AH, Weisdorf DJ. Infections in recipients of hematopoietic cell transplantation. In Mandell D, ed. Bennett’s Principles and Practice of Infectious Diseases, 7th edn. Philadelphia: Elsevier Churchill Livingston, 2010; pp. 3821-3837.

7. Grossi P, Farina C, Fiocchi R, Dalla Gasperina D. Prevalence and outcome of invasive fungal infections in 1,963 thoracic organ transplant recipients: a multicenter retrospective study. Italian Study Group of Fungal Infections in Thoracic Organ Transplant Recipients. Transplantation 2000;70:112–116.

Diamantis Kofteridis, George Samonis, Department of Internal Medicine, University Hospital of Heraklion Crete, Greece

An update on the laboratory microbiological diagnosis of invasive fungal infections

The frequency of fungal infections, especially of invasive fungal infections (IFIs), has risen dramatically in recent years. Early and accurate diagnosis of these infections is important for several reasons, including timely implementation of antifungal therapy and decreasing the unnecessary use of toxic antifungal agents. Unfortunately, a major obstacle to the successful treatment of IFIs is the lack of sensitive and specific methods for their early diagnosis. Standard approaches to the laboratory diagnosis of IFIs include: (i) direct microscopic examination in freshly obtained samples, (ii) histopathological demonstration of fungi within tissue sections, (iii) cultivation of the causative fungus and identification, and (iv) radiology. However, these approaches are often not sufficiently sensitive and/or specific to diagnose IFIs, and their usefulness depends on obtaining samples of deep tissues, which, in many cases, is not feasible because of the condition of the patient. These limitations have led to the development of alternative methods based on the detection of fungal components, such as fungal antigens and fungal nucleic acids, which sometimes are the only diagnostic tools for IFIs [1,2].

The galactomannan (GM) antigen is a component of the cell wall of Aspergillus spp. Quantification of this fungal component is considered to be the method for the specific diagnosis of invasive aspergillosis (IA) and, although it has limitations, it has been included as a mycological criterion of probable IA. Its main contribution has been its usefulness when combined with high-resolution computed tomography (CT) in the early diagnosis of IA in high-risk patients with oncohematological diseases. Determinations are made from serum samples or plasma, and it is advisable to carry out serial quantifications to increase specificity and early diagnosis. GM quantification in broncho-alveolar lavage (BAL) may be useful in both critically ill patients and patients with hematological disease. There have been many reports of false-positive GM results associated with the use of β-lactam antibiotics, especially piperacillin/tazobactam, in children colonized with Bifidobacterium spp. and in patients receiving GM-containing solutions. On the other hand, prior administration of antifungals, especially prophylaxis with itraconazole, decreases test sensitivity. In general, serial quantification of serum GM can be used by clinical laboratories to detect IA in patients with hematological malignancy who are at risk of this infection. Quantification of GM in other clinical samples (BAL, CSF) may also be useful in neutropenic and non-neutropenic patients (Table 1) [1,3,4].

1,3-β-D-glucan (BG), a cell-wall component of most fungal species, can be detected in blood during IFIs. The BG test (Fungitell, Associates of Cape Cod Inc., USA), is used as a diagnostic tool for the detection of a broad spectrum of fungal pathogens, with the exception of Mucorales and Cryptococcus neoformans. This test is currently used in combination with classical clinical, radiological and microbiological findings. It is included in the updated definition of probable IFI by the European Organization for the Research and Treatment of Cancer and Mycosis Study Group (EORTC/MSG) consensus. Two consecutive positive BG serum samples from patients with hematological malignancies, including allogeneic HSCT, strongly suggest the diagnosis of probable IFI with a very high specificity and a positive predictive value. However, despite the excellent specificity of the assay, the sensitivity of BG remains low, and a negative result cannot rule out a diagnosis of fungal disease. Moreover, the use of albumin, immunoglobulins and hemodialysis has been associated with false-positive results. BG is a helpful tool for the diagnosis of Pneumocystis jiroveci pneumonia in human immunodeficiency virus (HIV)-positive patients. In general, the BG detection test has been used less widely than the GM test, but its inclusion in the diagnostic criteria by EORTC/MSG may increase its use. The current trend is to recommend a combination of several diagnostic techniques to rule out fungal infections in patients at risk; therefore, the BG and GM combination could become the preferred strategy [1,3,4,5].

Mannan is a major component of the Candida cell wall that induces a strong antibody response. Therefore some authors have suggested that the combined detection of mannan (Platelia Candida Ag, Bio-Rad Laboratories) and anti-mannan antibodies (Platelia Candida Ab,

http://www.ncbi.nlm.nih.gov/pubmed/?term=pappas%2C+alexander%2C+andeshttp://www.ncbi.nlm.nih.gov/pubmed/?term=pappas%2C+alexander%2C+andesfile:///Users/eirenelazana/Documents/newsletter/e_bulletin/february_2013/english/../../AppData/Local/IATRIKI/papers/papers in preparation/IATRIKI/papers/papers in preparation/IATRIKI/Guidelines omada ergasias/UpToDate.19.3.PC/contents/mobipreview.htmfile:///Users/eirenelazana/Documents/newsletter/e_bulletin/february_2013/english/../../AppData/Local/IATRIKI/papers/papers in preparation/IATRIKI/papers/papers in preparation/IATRIKI/Guidelines omada ergasias/UpToDate.19.3.PC/contents/mobipreview.htmfile:///Users/eirenelazana/Documents/newsletter/e_bulletin/february_2013/english/../../AppData/Local/IATRIKI/papers/papers in preparation/IATRIKI/papers/papers in preparation/IATRIKI/Guidelines omada ergasias/UpToDate.19.3.PC/contents/mobipreview.htmhttp://www.ncbi.nlm.nih.gov/pubmed?term=Bodey G%5BAuthor%5D&cauthor=true&cauthor_uid=1396746http://www.ncbi.nlm.nih.gov/pubmed?term=Bueltmann B%5BAuthor%5D&cauthor=true&cauthor_uid=1396746http://www.ncbi.nlm.nih.gov/pubmed?term=Duguid W%5BAuthor%5D&cauthor=true&cauthor_uid=1396746http://www.ncbi.nlm.nih.gov/pubmed/?term=eur+j+clin+microbiol+infect+dis+1992%3B+11%3A+99-109http://www.ncbi.nlm.nih.gov/pubmed?term=Grossi P%5BAuthor%5D&cauthor=true&cauthor_uid=10919584http://www.ncbi.nlm.nih.gov/pubmed?term=Farina C%5BAuthor%5D&cauthor=true&cauthor_uid=10919584http://www.ncbi.nlm.nih.gov/pubmed?term=Fiocchi R%5BAuthor%5D&cauthor=true&cauthor_uid=10919584http://www.ncbi.nlm.nih.gov/pubmed?term=Dalla Gasperina D%5BAuthor%5D&cauthor=true&cauthor_uid=10919584

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Invited articles Invited articles

Bio-Rad Laboratories) considerably improves the diagnosis of candidemia. While individual sensitivities of these tests is low (0.5

1 single sample, positive cut-off index >0.7

A screening test to accompany conventional diagnostic methods in patients at high risk of IA.

In neutropenic adults

In neutropenic children

Serum value >1: sign of therapeutic failure in adults and children

Helps rule out IA because of the high % of negative predictive value (NPV) Quantification in BAL (cut-off >1) and CSF (cut-off >0.5) (useful in neutropenic and non-neutropenic patients)

In non-neutropenic patients: not the same diagnostic and prognostic value

Mold-active antifungal drug therapy is one of the factors that may have an impact on sensitivity

b-D-glucan

(BG)

Diagnosis of IFI

2 samples/week (minimum)

Pan-fungal marker in critically ill patients and in cases of P. jiroveci pneumonia

A frequency of 2 tests per week seems an appropriate screening strategy

increases the specificity but decreases the sensitivity

False-(+) results, methodological concerns

Limited experience (less widely used than GM)

The threshold for positive results depends on the test that is used:

• Fingitell >80 pg/mL

• Wako >7 pg/mL

Less accurate in hematological patients (significant limitation to use as a screening test)

Mannan plus anti-mannan

Candidemia Good sensitivity and specificity when combined Early diagnosis prior to blood culture results

Limited experience

Non-mycological criterion

Molecular methods (polymerase chain reaction; PCR)

DNA detection mainly of Aspergillus

Early diagnosis (rapid techniques)

High NPV

Additional techniques

Non-mycological criterion (they are still in development)

Limited to reference laboratories (low availability)

High cost

References:

1. Cuenca-Estrella M, Matteo B, Lass-Florl C, et al. Detection and investigation of invasive mould disease. J Antimicrob Chemother 2011;66(Suppl 1):i15-24.

2. Yeo SF, Wong B. Current status of nonculture methods for diagnosis of invasive fungal infections. Clin Microbiol Rev 2002;15:465-484.

3. De Pauw Β, Walsh TJ, Donnelly JP, et al. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis 2008;46:1813-1821.

4. Lamoth F, Cruciani M, Mengoli C, et al. β-Glucan antigenemia assay for the diagnosis of invasive fungal infections in patients with hematological malignancies: a systematic review and metaanalysis of cohort studies from the Third European Conference on Infections in Leukemia (ECIL-3). Clin Infect Dis 2012;54:633–643.

5. Cuenca-Estrella M, Verweij PE, Arendrup MC, et al. ESCMID guideline for the diagnosis and management of Candida diseases 2012: diagnostic procedures. Clin Microbiol Infect 2012;18(Suppl 7):9–18.

6. McLintock LA, Jones BL. Advances in the molecular and serological diagnosis of invasive fungal infection in haemato-oncology patients. Br J Haem Review 2004;126:289-297.

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Invited articles

7. Tomer A, Leonard L, Mical P. PCR diagnosis of invasive candidiasis: systematic review and meta-analysis. J Clin Microbiol 2011;49:665-670.

8. Carlo M, Mario C, Rosemary AB, et al. Use of PCR for diagnosis of invasive aspergillosis: systematic review and meta-analysis. Lancet Infect Dis 2009;9:89-96.

G. Vrioni, MD, PhD, Assistant Professor, Department of Microbiology, Medical School, University of Athens

HCDCP’s departments activities

Experiential educational programs held by HCDCP of Thessaloniki

Two experiential teacher-training programs for secondary education, entitled Transgender Relations-Sexual Education-HIV Infection, were completed in the states of Ioannina and Magnisia.

Similar programs have been taking place since 2002; in the Prefectures of Central Macedonia, Eastern Macedonia-Thrace and Thessaly, between 2002 and 2008, 455 primary and secondary education teachers were trained, and between 2008 and 2012, 409 secondary education teachers were trained. The total number of teachers trained so far is thus 864.

The goal of the 40-hour long experiential program was to increase knowledge and develop the skills, positive attitudes and positive motivation of the educators, in order to co-ordinate similar programs and health education interventions in the classroom.

The programs were based on experiential participation methods such as:

• experiential exercises for active participation of all members of the group• discussion in small groups (usually preceded with a story or an incident as a trigger)• question processes (open and clear questions) • brainstorming (elaboration, evaluation and reclassification of ideas in order of priority) • special experiential activities for understanding high-risk behaviors• case studies• group work. The number of educators that took part in the two programs was 44.

Ioannina, 13–18 November 2012

Volos, 29 January–3 February 2013

Fani Goma, Head of the HCDCP Office in Thessaloniki

22 23

Recent publications Recent publications

1. «Fungal Infections Associated with Contaminated Methylprednisolone Injections». Smith R.M. , Schaefer M. K., Kainer Μ. A, et all N Engl J Med 2012. DOI: 10.1056/NEJMoa1213978 Copyright© 2012 Massachusetts Medical Society

In this article it is presented an investigation into fungal infections associated with injections of preservative-free methylprednisolone acetate, which is administered for treatment of chronic pain, in the USA. The investigation begun in October 2012 and most of the 13,534 potentially exposed persons had been contacted. As of December 10, there were 590 reported cases of infection in 19 states, with 37 deaths (6%). As of November 26, laboratory evidence of Exserohilum rostratum was present in specimens from 100 case patients (17%). Additional data were available for 386 case patients (65%); 300 of these patients (78%) had meningitis. Analysis of preliminary data from this large multistate outbreak of fungal infections showed substantial morbidity and mortality, although the particular pathogen-fungus was not considered to infect humans, before.

Rapid public health actions included prompt recall of the implicated product, notification of exposed persons, and early outreach to clinicians. In addition, the (American) CDC promptly edited guidelines for tackling this newly emerged mycosis.

(www.cdc.gov/hai/outbreaks/clinitians/guidance.cns.html)

2. «ESCMID Guideline for the Diagnosis and Management of Candida Diseases». A. J. Ullmann, O. A. Cornely, J. P. Donnelly, M. Akova, M. C. Arendrup, S. Arikan-Akdagli, M. Bassetti, J. Bille,T. Calandra, E. Castagnola, J. Garbino, A. H. Groll, R. Herbrecht, W. W. Hope, H. E. Jensen, B. J. Kullberg,C. Lass-Flo¨ rl, O. Lortholary, W. Meersseman, G. Petrikkos, M. D. Richardson, E. Roilides, P. E. Verweij, C. Viscoli and M. Cuenca-Estrella_ for the ESCMID Fungal Infection Study Group (EFISG) Clin Microbiol Infect. 2012 Dec;18 Suppl 7.

An ESCMID task force (basically composed of members of the Society’s Fungal Infection Study Group, EFISG) finalized the ESCMID diagnostic and management/ therapeutic guideline for Candida diseases. These ESCMID guidelines provide guidance for clinicians in their daily decision-making process (see the Table below –grading of the recommendations strength).

The task force was divided into 5 sub-groups and each was responsible for the development of the following guidelines:

• Diagnostic procedures of the Candida diseasesESCMID guideline for the diagnosis and management of Candida diseases 2012: diagnostic procedures M. Cuenca-Estrella, P. E. Verweij, M. C. Arendrup et all

• Diagnosis and management of Candida diseases in non-neutropenic adult patients.

ESCMID guideline for the diagnosis and management of Candida diseases 2012: non-neu-tropenic adult patients O. A. Cornely, M. Bassetti, T. Calandra et all

• Diagnosis and management of Candida diseases in adults with haematological malignancies and after haematopoietic stem cell transplantation

ESCMID guideline for the diagnosis and management of Candida diseases 2012: adults with haematological malignancies and after haematopoietic stem cell transplantation (HSCT). A. J. Ullmann, M. Akova, R. Herbrecht, et all

• Prevention and management of invasive infections in neonates and children caused by Candida spp.

ESCMID guideline for the diagnosis and management of Candida diseases 2012: prevention and management of invasive infections in neonates and children caused by Candida spp. W. W. Hope, E. Castagnola, A. H. Groll, et all

• Diagnosis and management of Candida diseases in patients with HIV infection or AIDS.

ESCMID guideline for the diagnosis and management of Candida diseases 2012: patients with HIV infection or AIDS. O. Lortholary, G. Petrikkos, M. Akova, et all.

24 25

Future conferences and meeting

3. «Diagnosis and treatment of mucormycosis in patients with haematological malignancies: guidelines from the 3rd European Conference on Infections in Leukemia (ECIL 3)». Skiada A, Lanternier F, Groll AH, Pagano L, Zimmerli S, Herbrecht R, Lortholary O, Petrikkos GL. Haematologica. 2012 Sep 14. DOI: 10.3324/haematol.2012.065110

The European Conference on Infections in Leukemia, a panel of delegates of the European Group for Blood and Marrow Transplantation, the European Organization for Treatment and Research of Cancer, the European Leukemia Net and the Immunocompromised Host Society assigned experts in Hematology and Infectious Diseases to develop evidence-based recommendations for the diagnosis and treatment of mucormycosis, since there had not been any guidelines, in the past. Key recommendations are summarized here.

In the absence of validated biomarkers, the diagnosis of mucormycosis relies on histology and /or detection of the organism by culture from involved sites with identification of the isolate at the species level (no grading).

Antifungal chemotherapy, control of the underlying predisposing condition, and surgery are the cornerstones of management (level A II). Options for firstline chemotherapy of mucormycosis include liposomal amphotericin B and amphotericin B lipid complex (level B II). Posaconazole and combination therapy of liposomal amphotericin B or amphotericin B lipid complex with caspofungin are the options for second line treatment (level B II).

Surgery is recommended for rhinocerebral and skin and soft tissue disease (level A II).

Reversal of underlying risk factors (diabetes control; reversal of neutropenia; discontinuation/taper of glucocorticosteroids; reduction of immunosuppressants; discontinuation of deferroxamine) is important in the treatment of mucormycosis (level A II).

The duration of antifungal chemotherapy is not defined but guided by the resolution of all associated symptoms and findings (no grading). Maintenance therapy/secondary prophylaxis has to be considered in persistently immunocompromised patients (no grading).

George Petrikkos, Professor of Internal Medicine – Infectious Diseases, Athens University’s Medical School,

Philip Koukouritakis, Head of the e-health information Office, HCDCP

Recent publications

March 2013

2-3 March, 2013

Title: Donation of Organs: A Gift of Life

Country: GreeceCity: TripoliVenue: Mainalon Hotel Phone: + 30 210 8764725Website: http://www.gkad.gr

17-24 March, 2013

Title: Infectious Disease Review for the Primary Care Physician

Country: USACity: FloridaVenue: Cruise SeminarPhone: + 800 422 0711Website: http://www.continuingeducation.net/coursedescription.php?topic=Infectious_Disease_CME_Cruise_Caribbean_March_2013

21-22 March, 2013

Title: NGS for Drugs, Patients and Clinical Trials Conference

Country: USACity: CaliforniaVenue: Hilton Hotel, San Diego Phone: + 781 972 5400Website: http://www.healthtech.com/ngs-drug-development/

28-30 March, 2013

Title: 5th Congress of Pathology in Central Greece

Country: GreeceCity: LarissaVenue: Larissa ImperialPhone: + 30 26510 68610Website:http://www.conferre.gr/newsletter/pathologia_2013/04122012/index.html

30-31 March, 2013

Title: 9th Annual Seminar on Pediatrics

Country: GreeceCity: AthensVenue: Athens CollegePhone: + 30 210 8836002Website:http://medical.datanalysis.gr/place/greece/in/2013/march/

Office for Public and International relations, HCDCP

http://www.ncbi.nlm.nih.gov/pubmed/22983580http://www.ncbi.nlm.nih.gov/pubmed/22983580http://www.ncbi.nlm.nih.gov/pubmed/22983580http://www.gkad.gr

26 27

Outbreaks around the world Interview

Outbreak news, February 2013

Novel coronavirus infection [1,2]

As of 21 February 2013, the World Health Organization (WHO) has been informed of a total of 13 confirmed cases of human infection with novel coronavirus (NCoV), including seven deaths. One new confirmed case of infection has been diagnosed in Saudi Arabia. The patient was hospitalized on 29 January 2013 and died on 10 February 2013. Three new cases have been diagnosed in the United Kingdom in the last 10 days. The second and third cases were infected by human to human transmission, although the exact route of transmission is still under investigation by the United Kingdom authorities. WHO does not advise special screening at points of entry with regard to this event nor does it recommend that any travel or trade restrictions be applied.

References:

1. World Health Organization (WHO). Available at http://www.who.int/csr/don [accessed 1 March 2013]

2. European Centers for Disease Prevention and Control (ECDC). Severe Respiratory Disease Associated with a Novel Coronavirus: Rapid Risk Assessment. Available at http://www.ecdc. europa.eu/en/press/news/Lists/News/ [accessed 1 March 2013]

Travel Medicine Office, Department for Interventions in Health Care Facilities

Georgios Petrikos Professor in Pathology, Infectious Diseases, University of Athens Medical School

Professor, what encouraged you to become involved with mycoses?

My decision to deal with fungus, especially with systematic (invasive) mycosis, occurred about 20 years ago when the occurrence of these infections started to ‘rise’ and I realized that there was a gap in clinical mycosis study in Greece. At that time the only person who was significant in the field was Professor Urania Marselou-Kidi, who of course was a pioneer in Greece. Thus, in co-operation with other people such as G. Samonis, E. Roilides, E. Fragouli, E. Mitrousia-Ziuva, we established the Hellenic Company of Medical Mycosis Study.

How do mycoses affect public health?

These days, penetrating mycoses are the fourth most common pathogenic factor in hospitals and their epidemiology is constantly changing. Unfortunately, the numbers of those who are likely to get infected, immune-suppressed patients, are constantly increasing, and the mortality rate, for the same reason, remains at high levels. Treatment is not easy and the sparse medication that exists against mycoses is often ineffective.

What are the most important infections that are caused by fungus?

The most important fungous infections are candidiasis, aspergillosis, cryptococcosis, mucormicosis and fousariosis, plus some others that have appeared recently.

Do we face new mycoses in Greece as much as at an international level?

We face new mycoses in Greece as much as internationally. Some are known fungi that in the past were considered responsible only for superficial infections (such as dermatitis), but there are other fungi whose pathogenic factors are not known to us. Today, every fungus is studied in the laboratory, and for immune-suppressed patients every fungus should be treated as a possible pathogenic factor.

What do you foresee regarding a cure for mycoses?

The treatment of mycoses in the future will be based on three main factors:

• prompt and precise diagnosis• restoration and re-enforcement of the host’s defense mechanisms• immediate, targeted treatment with new, less toxic medication, given either orally or parenterally.

28 29

Interview

What do you consider are the challenges facing the diagnosis of mycoses in Greece?

Especially for Greece, the challenges as far as prompt and precise diagnoses are concerned are:

• continuous information for and training of medical students and doctors regarding the peculiarities of these infections

• good clinical doctors who can diagnose in good time the first clinical manifestations of mycoses and exploit the potential offered nowadays by the work of specialized laboratories in order to identify the mycosis promptly and verify the cause of the disease

• the existence and operation of a specialized reporting center, in every developed country, providing immediate support for the clinical diagnosis and treatment of mycoses

• well-organized epidemiological studies and the creation of a network to record all systematic mycoses so that we are aware of the real extent of the problem in our country and are able to develop the right strategies to confront it.

Let us change the style of the interview now for a more personal point of view. Following a long and important road in your field, can you share some significant moments with us? Anything that has remained with you?

What really strikes me as important and, I believe, determined my career, was when my highly respected tutor, Georgios Daikos, chose me as his partner in 1975.

What’s more, I will never forget the important research, carried out under difficult circumstances, with Professor E. Giamarellou and other collaborators at the Research Laboratory for Infectious Diseases and Antimicrobial Chemotherapy, in the basement laboratories of the Medical School.

I have a strong memory of my first encounter with a patient with fatal mucormicosis. I dealt with the disease such that we are now considered to be pioneers in the recording of this disease (zygomyco.net).

Finally, where do you think that infectious disease study will lead, in our country and internationally? What would you advise new scientists who decide to specialize in infectious disease studies or public health in general?

Infectious diseases are considered internationally to be one of the most important specialties, and preoccupy the whole scientific community and governments as well as international organizations for public health.

There is a constant need to further expertise in this specific sector and to maintain a collaboration amongst different doctor specialties, because of epidemics caused by new pathogens, the re-appearance of old, forgotten infections, and problems caused by the resistance of microbes as a result of the use of antibiotics along with the lack in new antimicrobials and the increase in patients who are highly vulnerable to microbes. Infectious disease specialists along with clinical microbiologists will form the foundation for solving the problems in public health caused by infections.

My advice for new scientists who decide to become involved in the field of infectious diseases is to do so out of a love of and deep interest in the patient, bearing in mind that, unlike other diseases, infections can be cured or even eliminated by using the correct treatment and preventative actions.

We thank you a lot.

Edited by Philip Koukouritakis

Myths and truths

Myths and Truths about Fungal Infections

Myths Truths

Observation of the halo-sign and air-crescent sign by com-puted tomography (CT) in im-munocompromised patients is diagnostic of invasive pulmo-nary aspergillosis

Infections resulting from other angio-invasive filamen-tous fungi, such as Zygomycetes, Fusarium species and Scedosporium species, as well as Pseudomonas aerugi-nosa and Nocardia species, may cause a halo sign and other radiological features as described for aspergillosis

The duration of aspergillosis treatment should be deter-mined by normalization of ga-lactomannan antigenemia

The duration of aspergillosis treatment should be deter-mined not solely by normalization of antigenemia but also by resolution of clinical and radiological findings. The use of serial galactomannan for therapeutic monitoring remains investigational

Any of the known antifungal agents may be used for the treatment of invasive aspergil-losis

Voriconazole and liposomal amphotericin B are the main compounds for primary treatment of invasive aspergil-losis

Identification of any species of the genus Candida in one blood culture is enough to establish a diagnosis of candidemia

Candidemia is defined as the presence of any species of the genus Candida in the blood. However, subsequent blood cultures are essential for diagnosing candidemia

Fluconazole is recommended as the initial therapy for all pa-tients with candidemia

In non-neutropenic patients, fluconazole or an echinocandin is recommended as the initial therapy for most adults with candidemia. An echinocandin is favored for patients with moderately severe to severe illness or patients who have had recent azole exposure. Fluconazole is recommended for patients who are less critically ill or who have no recent azole exposure. The same therapeutic approach is advised for children with attention to differences in dosing regimens.

In neutropenic patients an echinocandin is recommended for most patients

The recommended duration of therapy for candidemia is 2 weeks

The recommended duration of therapy of candidemia without obvious metastatic complications is 2 weeks after documented clearance of Candida from the bloodstream (i.e. a negative blood culture) and resolution of symp-toms attributable to candidemia

In patients with candidemia in-travenous catheters should be removed.

In non-neutropenic patients and in neonates with candi-demia, intravenous catheter removal is strongly recom-mended.

In neutropenic patients with candidemia, intravenous catheter removal should be considered

http://zygomyco.net

30 31

References:

1. Walsh TJ, Anaissie EJ, Denning DW, et al. Treatment of aspergillosis: clinical practice guidelines of the Infectious Disease Society of America. Clin Infect Dis 2008;46:327-360.

2. Pappas PG, Kauffman CA, Andes D, et al. Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Disease Society of America. Clin Infect Dis 2009;48:503-535.

3. Cuenca-Estrella M, Verweij PE, Arendrup MC, et al. ESCMID guideline for the diagnosis and management of Candida disease 2012: diagnostic procedures. Clin Microbiol Infect 2012;18(Suppl 7):9-18.

4. Cornely OA, Bassetti M, Calandra T, et al. ESCMID guideline for the diagnosis and management of Candida disease 2012: non-neutropenic patients. Clin Microbiol Infect 2012;18(Suppl 7):19-37.

5. Ullmann AJ, Ankova M, Herbrecht R, et al. ESCMID guideline for the diagnosis and management of Candida disease 2012: adults with haematological malignancies and after haematopoietic stem cell transplantation (HCT). Clin Microbiol Infect 2012;18(Suppl 7):53-67.

Aspasia Katragkou and Emmanuel Roilides, 3rd Department of Pediatrics, Aristotle University School of Medicine

Myths and truths News from the HCDCP’s administration

Distinction award for Professor Constantina Politis by the International Haemovigilance Network (IHN)

The International Haemovigilance Network (IHN) and all the member organizations affiliated with this network have unanimously honored Professor Constantina Politis, Head of the Co-ordinating Hemovigilance Center and Scientific Advisor for the Hellenic Center for Disease Control and Prevention (HCDCP), by distinguishing her for her outstanding and sustained commitment to the field of hemovigilance.

The award presentation took place in Brussels on 22 February 2013 at a special ceremony during the course of the 15th International Hemovigilance Seminar. The IHN award consists of a statue designed and modeled by a Dutch artist and a token monetary prize. IHN recognizes Professor Politis’ work at a national level, where she has been instrumental in building-up a national hemovigilance system within Greece that has, for several years now, generated valuable data and information that have contribute to increased safety along the blood chain. At an international level, Professor Politis has made her voice heard at the European Commission, the Council of Europe and many other organizations, not only on topics related to hemovigilance but also in general on quality and safety issues related to blood transfusion.

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Quiz of the month

?What is the most common fungal infection of immunocompromised patients?

A) Aspergillosis

B) Infection by younger fungi

C)Candidiasis

Send your answer to the following e-mail: info-quiz@keelpno.gr

The answer to January’s quiz was: the original name of norovirus was Norwalk virus. It was named after the first epidemic that was attributed to it in 1968, in a primary school in the city of Norwalk, northern Ohio, USA

Nine people answered correctly.

Chief Editor:Ch. Hadjichristodoulou

Scientific Board:Ν. VakalisΕ. VogiatzakisP. Gargalianos- KakolirisΜ. Daimonakou- VatopoulouΙ. LekakisC. LionisΑ. PantazopoulouV. PapaevagelouG. SaroglouΑ. Tsakris

Editors:Τ. Kourea- KremastinouHCDCP President

T. PapadimitriouHCDCP Director

Editorial Board:

R. VorouE. KaratampaniP. KoukouritakisΚ. MellouD. PapaventsisΤ. PatoucheasV. RoumeliotiV. SmetiCh. TsiaraΜ. FotineaΕ. Hadjipashali

Graphic Design:

Ε. Lazana

Copy Editor:

P. Koukouritakis

Associate Editors:

P. KoukouritakisΜ. Fotinea

mailto:info-quiz@keelpno.gr