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DIAGNOSE EN SURVEILLANCE VAN INFECTIEUZE AANDOENINGEN DIAGNOSTIC ET SURVEILLANCE DES MALADIES INFECTIEUSES Cultureel en Congrescentrum van St.-PietersWoluwe Centre Culturel et de Congrès de Woluwé-St-Pierre INFORMATION | INFORMATIE T +32 2 642 57 77 Inscription avant le 10 novembre 2011 Inschrijving vóór 10 november 2011 sur | op www.wiv-isp.be/epidemio/labo PROGRAMME | PROGRAMMA Diagnosis TB Invasive mycoses Surveillance Tools for infectious diseases Infectious diseases in the elderly Cat scratch disease Risk & Prevention Norovirus EUCAST breakpoints DEVANI project Infection control HCAI Waterborne diseases Responsible editor: Dr J . Peeters | General director | Rue J. Wytsmanstraat 14 | 1050 Brussels 27STE SEMINARIE > 24 NOVEMBER 2011 27E SÉMINAIRE > 24 NOVEMBRE 2011 Dit seminarie kwam tot stand dankzij de medewerking en financiële steun van de : Ce séminaire est organisé grâce collaboration et à l’appui financier de : Didactisch materiaal – Matériel didactique Siemens Healthcare Diagnostics Stands Advertenties / Publicités Abbott Molecular AstraZeneca Alere Health Becton Dickinson AstraZeneca Bio-Rad Laboratories Becton Dickinson Cepheid Benelux Biocodex Benelux Meridian Bioscience Europe BioMérieux Benelux Sanofi Pasteur MSD Bio-Rad Laboratories Siemens Medical Solutions Diagnostcis Cepheid Benelux CSS-HGR International Medical Products Lameris Lucron Bioproducts Meridian Bioscience Europe Oxoid Siemens Healthcare Diagnostics Organiserend Comité – Comité Organisateur Voorzitter / Président : Dr S. QUOILIN (WIV-ISP) Dr. J. BOTS (GGC) Dr P. BUTAYE (CODA) Dr. B. CATRY (WIV-ISP) Dr G. DAUBE (ULg) Dr P. MELIN (ULg) Dr. E. PADALKO (UGent) Dr. D. PIERARD (UZ Brussels) Dr C. POTVLIEGE (CH Tivoli) Dr. K. DE SCHRIJVER (Vl. Gem.) Mme G. DUCOFFRE (WIV-ISP) Dr P. GOUBAU (UCL) Dr. G. IEVEN (UZA) Dr. Y. VAN LAETHEM (CHU St-Pierre) Dr. H. VAN OYEN (WIV-ISP) Dr. J. VERHAEGEN (UZ Leuven) Dr. K. VERNELEN (WIV-ISP) Rédacteur en chef – Eindredacteur Mme G. DUCOFFRE Seminarie brochures – Brochures du séminaire Drukkerij WIV-ISP – Imprimerie WIV-ISP à la Table des matières – Inhoud • • • • • • Mandatory Declaration of Infectious Diseases, the Brussels experience Dr J. Bots ................................................................................................................................................. 1 Kick-off of the National Reference Centers Dr G. Muyldermans ……………………………………………………………………………………….......... 3 Monitoring the immunisation coverage in the general population: the contribution of a health interview survey Dr J. Van Der Heyden ............................................................................................................................. 5 Update on the introduction of EUCAST breakpoints in Belgium Dr J. Van Eldere ...................................................................................................................................... 7 Tuberculosis rapid diagnostic tests: what is new? Dr M. Fauville-Dufaux .............................................................................................................................. 9 Clinical outcomes of health-care-associated infections and antimicrobial resistance in patients admitted to European intensive-care units: a cohort study Dr M.-L. Lambert ..................................................................................................................................... 11 • Norovirus outbreaks in hospitals: epidemiology, diagnostic, management and control Dr P. Huynen ........................................................................................................................................... • • • • • 13 Cat Scratch Disease and Bartonellosis : clinical and diagnostic aspects Dr P. Goubau ........................................................................................................................................... 15 Group B streptococci, an European perspective with results of the DEVANI project Dr P. Melin ............................................................................................................................................... 17 Waterborne diseases and outbreaks associated with drinking water Dr K. De Schrijver..................................................................................................................................... 19 Infectious diseases in the elderly Dr J. Flamaing.......................................................................................................................................... 21 Diagnostic criteria for invasive mycoses Dr D. Vogelaers ........................................................................................................................................ 23 Programme 8.00 Registration with walking breakfast / Visit of stands Session 1 Chairpersons: Dr Y. Van Laethem (CHU St-Pierre) and Prof. Dr H. Van Oyen (WIV-ISP) 09.30 Surveillance tools for infectious diseases: Mandatory Declaration of Infectious Diseases, the Brussels experience - Dr J. Bots (GGC) Kick-off of the National Reference Centers - Dr G. Muyldermans (WIV-ISP) Monitoring the immunisation coverage in the general population: the contribution of a health interview survey - Dr J. Van Der Heyden (WIV-ISP) 10.05 Update on the introduction of EUCAST breakpoints in Belgium Dr J. Van Eldere (UZ Leuven) 10.30 Tuberculosis rapid diagnostic tests: what is new? Dr M. Fauville-Dufaux (WIV-ISP) 10.55 Coffee break / Visit of stands Session 2 Chairpersons: Dr C. Potvliege (CH Tivoli) and Dr D. Pierard (UZ Brussel) 11.25 12.00 12.30 Clinical outcomes of health-care-associated infections and antimicrobial resistance in patients admitted to European intensive-care units: a cohort study Dr M.-L. Lambert (WIV-ISP) Norovirus outbreaks in hospitals: epidemiology, diagnostic, management and control Dr P. Huynen (CHU Liège) Lunch Session 3 Chairpersons: Dr O. Denis (Hôp. Erasme) and Dr E. Padalko (UZ Gent) 16.00 Cat Scratch Disease and Bartonellosis : clinical and diagnostic aspects Dr P. Goubau (CHU St-Luc Bruxelles) Group B streptococci, an European perspective with results of the DEVANI project Dr P. Melin (CHU Liège) Waterborne diseases and outbreaks associated with drinking water Dr K. De Schrijver (Vlaamse Gemeenschap) Infectious diseases in the elderly Dr J. Flamaing (UZ Leuven) Diagnostic criteria for invasive mycoses Dr D. Vogelaers (UZ Gent) Closing address 16.15 End of seminar 14.00 14.25 14.50 15.15 15.35 Mandatory Declaration of Infectious Diseases, the Brussels experience Dr. J. Bots Gemeenschappelijke Gemeenschapscommissie Louizalaan, 183 – 1050 Brussel [email protected] Introduction • The purpose of declaring infectious diseases to the health inspectorate is to be sure that sufficient effort is taken to limit further propagation of infectious diseases. • All too often clinicians and laboratories do not declare to the health inspectorate cases of infectious diseases in which a timely intervention can limit spread of the disease. • Clinicians and laboratory personnel are not supposed to be experts in this matter neither do they have sufficient time to manage the prophylaxis. • Mandatory notification to a health inspectorate, possibly leading to timely intervention, is different from reporting to a surveillance system which primary objective is to collect data for the authorities. Conclusion In order to achieve a satisfactory level of mandatory notification we visit stakeholders (laboratories, hospital hygienists, associations of GP’s) to convince them of the importance of performing their (legal) duties. An easy to use electronic tool for on line declaration was established. The Brussels law has also been updated in accordance with privacy- and European regulations, but a continuous effort will be necessary. 1 2 Kick-off of the National Reference Centers Dr. G. Muyldermans WIV-ISP, Public Health and Surveillance J. Wytsmanstreet, 14 - 1050 Brussels [email protected] Recently, 35 national reference centers (NRC) for different pathogens or groups of pathogens were installed in Belgium to fulfill the following core functions: offering reference diagnostics, collecting reference materials, sharing information and scientific advice, participating to national and international networks, collaborating with research workgroups, and contributing to surveillance activities. In order to offer the reference diagnostics, minimum testing requirements will be elaborated. Technical guidance on appropriate sampling for diagnosis of infection and further characterization of human pathogens of public health relevance will be offered. The NRC will take a leader role in the evaluation of new diagnostic or typing assays by the follow-up of new techniques and the evaluation and validation of these assays. Similarly, the NRC plays a key role in the collection of relevant reference materials. The NRC will be prepared in case an emerging disease occurs in terms of the infrastructure, strain identification and typing and specialist capabilities. An efficient and effective manner to communicate the aggregated information back to the data providers will be put in place by the WIV-ISP. An automated and timely reporting is foreseen. In case of an epidemic or outbreak, automated alerting based on defined threshold levels will be released. Furthermore, the implementation of a centrally coordinated network through the national NRC has an added value by bringing all expertise together. The NRC will report accurate and comparable microbiology data to international surveillance systems in compliance with case definitions and surveillance protocols. Also, the nomination of NRC will render the laboratory a national spokesman role and thereby a scientific recognition for initiating national and international collaborations. To summarize, the implementation of the NRC will reinforce the public health microbiology in Belgium due to the closer cooperation between the clinical laboratories and the WIV-ISP. 3 4 Monitoring the immunisation coverage in the general population: contribution of the health interview survey Dr. J. Van der Heyden and Dr J. Tafforeau WIV-ISP, Public Health and Surveillance J. Wytsmanstreet, 14 - 1050 Brussels [email protected] The relevance of the immunisation programmes has been to a large extent demonstrated. Consequently, the WHO recommends to gather data about immunisation coverage periodically. In Belgium several sources exist or have been used to measure the immunisation coverage: − − − − − − surveys within specific population groups: children of 18 to 24 months, school children, elderly people in institutions, sex workers, health care workers; data gathered in the framework of medical school visits; health insurance data; sales statistics; sentinel networks of general practitioners; Vaccinnet, a centralised electronic database in Flanders for the purchase of vaccines and registration of immunised persons. A general health interview survey (HIS) is a complementary data source to these existing instruments. As immunisation coverage surveys among infants of 18 to 24 months are performed periodically in Belgium, it is not necessary to repeat such measurement in the framework of the health survey. Moreover, for methodological reasons it would be difficult to estimate immunisation coverage among infants with the general HIS, for the number of individuals in the target age group is too small (approximately 200) to be able to draw any conclusions. Despite the lack of information for school aged children immunisation coverage among those can also hardly be measured via general population surveys because, just as for infants, the number of individuals in the target age group is too limited. The general adult population is clearly the one for which data on immunisation status is missing and for which the HIS is helpful. In Belgium HIS’s have been organised in 1997, 2001, 2004 and 2008. In each survey questions on immunisation have been included. Information was collected on vaccination against tetanus, hepatitis B, influenza, pneumococcus, diphtheria, meningococcus C and rubella, although the types of vaccines for which information was gathered varied by survey. The main objective of the HIS as far as immunisation is concerned is thus to provide estimates about the vaccination coverage among adults. As the information is self-reported, questions may be raised with respect to the validity of the estimates. On the other hand a general population survey allows to: − study the immunisation coverage in function of socio-demographic background characteristics − study the immunisation coverage for specific target groups (e.g. influenza coverage for chronic patients) − follow the evolution over time, both in the general population and within subgroups − collect information on the circumstances in which a person has been immunised (e.g. on the recommendation of a health care provider, on his own initiative, following an information campaign,...) − collect information on reasons why people do not want to be immunised. During the presentation some of these issues will be illustrated with examples from the Belgian HIS. Key references Van Oyen H, Tafforeau J, Hermans H, Quataert P, Schiettecatte E, Lebrun L et al. The Belgian Health Interview Survey. Arch Public Health 1997; 55:1-13. 1 Tafforeau J. La Vaccination . In ““Gisle L, Hesse E, Drieskens S, Demarest S, Van der Heyden J, Tafforeau J. Enquête de Santé 2008, Rapport II. Style de vie et prévention, Direction opérationelle Santé Publique et Surveillance, Institut Scientifique de Santé Publique, Bruxelles, 2010“ - p 596-682. 1 https://www.wiv-isp.be/epidemio/epifr/CROSPFR/HISFR/his08fr/r2/9.la%20vaccination_r2.pdf 5 6 Update on the introduction of EUCAST breakpoints in Belgium Dr. J. Van Eldere UZ Leuven Herestraat, 49 – 3000 Leuven [email protected] On behalf of the Belgian national antibiotic committee, a questionnaire was sent in April 2011 by the IPH ( WIV-ISP) to all labs in Belgium that are known to perform microbiological testing. This questionnaire was intended to assess whether they used EUCAST breakpoints for antimicrobial susceptibility testing and the reasons for using EUCAST breakpoints. More than 80% of the labs responded; analysis of the data shows that introduction of EUCAST breakpoints is still not fully accomplished in Belgium. Many labs are still using different versions of CLSI breakpoints. Several reasons are given ; the lack of EUCAST breakpoints for some antibiotics or the fact that the labs just follow the advice of the AST manufacturer. The Belgian NAC has meanwhile worked on defining breakpoints for antibiotics that do not have EUCAST breakpoints, on putting together roadmap documents for labs wanting to introduce EUCAST breakpoints, on quality control for EUCAST AST and has helped AST manufacturers in defining the antibiotics to be tested in Belgium. In the last year the EUCAST subcommittee on antifungal susceptibility testing has made progress in defining antifungal breakpoints. Subcommittees on expert rules for antimicrobial susceptibility testing and antimicrobial susceptibility testing of anaerobes have completed their tasks. Most antimicrobial MIC breakpoints in Europe have been harmonized by EUCAST. EUCAST breakpoints are now available in most devices for automated susceptibility testing but with some limitations, depending on the system. A disk diffusion susceptibility test method calibrated to EUCAST MIC breakpoints is now also available. 7 8 Tuberculosis rapid diagnostic tests: what is new? Dr M. Fauville-Dufaux WIV-ISP – Maladies bactériennes Rue Engeland, 642 – 1180 Bruxelles [email protected] The laboratory confirmation of the TUBERCULOSIS DISEASE in humans is still based on the isolation of mycobacteria of the Mycobacterium tuberculosis complex and cannot be done by serology. The detection of a TUBERCULOUS INFECTION, after contamination and before evolution to the active disease, is based on the host’s stimulated cellular immunity. th The unexpected resurgence of tuberculosis (TB) the last 20 years of the 20 century and the emergence of multi- and more recently ultra-drugresistant strains stimulated the progress in diagnosis methods which were remained practically unchanged for many decades. The most important developments in the microbiological diagnosis of active tuberculosis concern automated culture methods in selective liquid media and the important development of molecular techniques directly used on the specimens or on positive cultures. Culture remains the highest sensitive method (detection limit of 100 bacilli/ml) and therefore the golden standard for isolation of mycobacteria from clinical samples. The bacterial growth in liquid media is clearly faster and more sensitive than on solid media and the use of automated systems is easy. They are also used to perform “rapid” drug susceptibility testing. Molecular techniques are used on clinical specimens but also on positive cultures for the detection and specific identification of nucleic acids of the different mycobacterial species, for the detection of gene mutations associated with resistance to drugs and for the determination of the genetic fingerprint of the isolates when an epidemic is suspected. Fingerprinting is also used to differentiate a relapse of TB in a patient from a new exogenous contamination and to rule out false positives when a laboratory crosscontamination between specimens is suspected. Used directly on clinical samples, the molecular techniques are less sensitive (detection limit >1000 bacilli/ml) but more rapid than culture. They are more sensitive and more specific than the direct microscopic examination. Nowadays the most advanced available test is the GenXpert MTB/RIF assay allowing the simultaneous detection on sputa, within 2 hours, of M.tuberculosis DNA and mutations associated with rifampicin resistance. Other new techniques are the rapid chromatographic immunoassay for the identification of M.tuberculosis in positive cultures and the use of mass spectrometry for the analysis of the cell wall of mycobacteria. 4 Near these modern methods, smear microscopy (detection limit > 10 bacilli/ml) remains the first one performed in the laboratory, preferentially after fluorochrome staining, because it is rapid, cheap and a smear positive result constitutes an information on the contagiousness of the patient Concerning the diagnosis of latent tuberculous infection (LTBI), without clinical manifestation and radiological or bacteriological evidence of active disease, the new diagnostic tests recently commercialized are the IGRA’s (Interferon-Gamma Release Assays). These in vitro tests are more specific than the classical tuberculin skin test and give less false positives. They may be used in conjunction with an overall risk assessment in order to identify individuals for whom preventive treatment should be considered. In Belgium, they don’t replace the tuberculin skin test for contact tracing of a tuberculosis patient because of their higher cost, but they are recommended for the control of BCG-vaccinated persons or to confirm a positive tuberculin-skin test. They are not recommended for the diagnosis of active tuberculosis. In this talk, I will review the recent available diagnostic tests, their advantages and limits. References Mastering the basics of TB control. Development of a handbook on TB diagnostic methods. European Centre for Disease Prevention and Control, Technical report, Stockholm, 2011. http://www.ecdc.europa.eu/en/publications/Publications/Forms/ECDC_DispForm.aspx?ID=676 Use of interferon-gamma release assays in support of TB diagnosis. European Centre for Disease Prevention and Control, Guidance, Stockholm, 2011. http://ecdc.europa.eu/en/publications/Publications/1103_GUI_IGRA.pdf Tuberculosis 2007. From basic science to patient care. Ed: Palomino JC., Leäo SC, Ritacco V. http://www.tuberculosistextbook.com 9 10 Clinical outcomes of health-care-associated infections and antimicrobial resistance in patients admitted to European intensive-care units: a cohort study Dr M.-L. Lambert WIV-ISP, Public Health and Surveillance J. Wytsmanstreet, 14 - 1050 Brussels [email protected] Background Patients admitted to intensive-care units are at high risk of health-care-associated infections, and many are caused by antimicrobial-resistant pathogens. We aimed to assess excess mortality and length of stay in intensive-care units from bloodstream infections and pneumonia. Methods We analysed data collected prospectively from intensive-care units that reported according to the European standard protocol for surveillance of health-care-associated infections. We focused on the most frequent causative microorganisms. Resistance was defined as resistance to ceftazidime (Acinetobacter baumannii or Pseudomonas aeruginosa), third-generation cephalosporins (Escherichia coli), and oxacillin (Staphylococcus aureus). We defined 20 different exposures according to infection site, microorganism, and resistance status. For every exposure, we compared outcomes between patients exposed and unexposed by use of timedependent regression modelling. We adjusted results for patients’ characteristics and time-dependency of the exposure. Findings We obtained data for 119 699 patients who were admitted for more than 2 days to 537 intensive-care units in ten countries between Jan 1, 2005, and Dec 31, 2008. Excess risk of death (hazard ratio) for pneumonia in the fully adjusted model ranged from 1·7 (95% CI 1·4–1·9) for drug-sensitive S aureus to 3·5 (2·9–4·2) for drug-resistant P aeruginosa. For bloodstream infections, the excess risk ranged from 2·1 (1·6–2·6) for drugsensitive S aureus to 4·0 (2·7–5·8) for drug-resistant P aeruginosa. Risk of death associated with antimicrobial resistance (ie, additional risk of death to that of the infection) was 1·2 (1·1–1·4) for pneumonia and 1·2 (0·9–1·5) for bloodstream infections for a combination of all four microorganisms, and was highest for S aureus (pneumonia 1·3 [1·0–1·6], bloodstream infections 1·6 [1·1–2·3]). Antimicrobial resistance did not significantly increase length of stay; the hazard ratio for discharge, dead or alive, for sensitive microorganisms compared with resistant microorganisms (all four combined) was 1·05 (0·97–1·13) for pneumonia and 1·02 (0·98–1·17) for bloodstream infections. P aeruginosa had the highest burden of healthcare-acquired infections because of its high prevalence and pathogenicity of both its drug-sensitive and drug-resistant strains. Interpretation Health-care-associated bloodstream infections and pneumonia greatly increase mortality and pneumonia increase length of stay in intensive-care units; the additional effect of the most common antimicrobial resistance patterns is comparatively low. 11 12 Norovirus outbreaks in hospitals: epidemiology, diagnostic, management and control Dr P. Huynen Medical Microbiology Laboratory, University Hospital of Liège Sart-Tilman, Bât. 23 - 4000 Liège [email protected] Noroviruses (NoV) are single-stranded RNA, non enveloped viruses belonging to the family of the Caliciviridae . The genus NoV has been separated in five genogroups, designated GI through GV. Three of these, namely GI, II and IV, are pathogenic to humans. Each genogroup contains several genotypes. A single genotype, GII.4, is associated with the majority of global outbreaks. Within the last years, several NoV outbreaks occurred and were documented in Belgium hospitals. After an average incubation from 12 to 48 hours, NoV illness is characterized by acute-onset vomiting, watery non-bloody diarrhoea with abdominal cramps, and nausea. Recovery is usually complete after 2 or 3 days. However, more prolonged courses of illness and viruses shedding can occur, particularly among young children, elderly persons and hospitalized patients. NoV are transmitted primarily through the fecal-oral route, either by direct person-to-person spread or fecally contaminated food or water. NoV can also spread via a droplet route from vomitus. NoV are now recognized as the leading cause of epidemics of gastroenteritis, and represent an important cause of sporadic gastroenteritis in both children and adults. The characteristics of NoV facilitate their spread during outbreaks: NoV are highly contagious; these viruses are relatively stable in the environment and can survive freezing and heating to 60°C; shedding may last several weeks; carrier may be asymptomatic; no or limited long-term immunity results from infection. Diagnosis of NoV infection relies on the detection of viral RNA in the stools of affected persons, by use of reverse transcription-polymerase chain reaction (RT-PCR) assays. Sequencing of NoV strains found in clinical and environmental samples greatly helps in conducting epidemiologic investigations. Commercial enzyme-linked immunoassays detecting NoV antigen currently exhibit inadequate sensitivity (<50%) to be useful for diagnosis of sporadic cases. However, in outbreak settings, these tests may be useful to rapidly identify NoV as the likely aetiology. Because of the limited availability of timely and routine laboratory diagnostic methods, a clinical diagnosis of NoV infection is often used. The Outbreak Kaplan Criteria are very specific—when all four criteria are present, there is a high likelihood that the outbreak is attributable to NoV. There is no specific drug to treat people with NoV infection. Symptomatic therapy consists of replacing fluid losses and correcting electrolyte disturbances. No vaccine is available. in Belgium, the Superior Health Council recommends to apply general precautions in our daily practice. Appropriate hand hygiene is likely the most important method to prevent NoV infection and control transmission. Ethanol-based hand sanitizers (≥62% ethanol) may be helpful as an adjunct method of hand hygiene, but should not replace washing with soap and water. In case of hospital outbreak, the Belgian Superior Health Council advises to implement additional contact (and droplets if needed) precautions. Several key approaches to interrupt NoV spread followed by most of European countries are fully described by the Centers for Disease Control and Prevention (USA). They consist mainly in managing patients with suspected NoV infection with careful attention to hand hygiene practice, cleaning and disinfecting the contaminated environmental surfaces. Strict control measures, including isolation or cohorting of symptomatic patients, exclusion of affected staff, and restricting new admissions in affected units are disruptive and costly but might be required to curtail outbreaks. Therefore, in front of a gastroenteritis outbreak, think norovirus, as it has a considerable public health impact. It is important to diagnose rapidly a beginning NoV outbreak in order to apply as soon as possible prevention measures to limit NoV spread. References 1. Zheng DP, Ando T, Fankhauser RL, Beard RS, Glass RI, Monroe SS. Norovirus classification and proposed strain nomenclature. Virology 2006;346:312--23. 13 2. Verbelen V et al. Hospital outbreak of gastroenteritis due to norovirus in Belgium. Acta Clinica Belgica 2004;59-1:30--33. 3. Siebenga JJ, Vennema H, Zheng DP, et al. Norovirus illness is a global problem: emergence and spread of Norovirus GII.4 Variants, 2001--2007. J Infect Dis 2009;200:802--12. 4. Lopman BA, Reacher MH, Vipond IB, Sarangi J, Brown DW. Clinical manifestation of norovirus gastroenteritis in health care settings. Clin Infect Dis 2004;39:318--24. 5. Henke-Gendo et al. New real-time PCR detects prolonged norovirus excretion in highly immunosuppressed patients and children. J Clin Microbiol 2009;47:2855--2862. 6. Westhoff TH, Vergoulidou M, Loddenkemper C, et al. Chronic norovirus infection in renal transplant recipients. Nephrol Dial Transplant 2009;24:1051--3. 7. Scallan E, Hoekstra RM, Angulo FJ, et al. Foodborne illness acquired in the United States---major pathogens. Emerg Infect Dis 2011;17:7--15. 8. Patel MM, Widdowson MA, Glass RI, Akazawa K, Vinje J, Parashar UD. Systematic literature review of role of noroviruses in sporadic gastroenteritis. Emerg Infect Dis 2008;14:1224--31. 9. Stals A. et al. Multiplex real-time RT-PCR for simultaneous detection of GI/GII noroviruses and murine norovirus 1. J Virol Methods 2009;161:247--253 10. Dimitriadis A, Marshall JA. Evaluation of a commercial enzyme immunoassay for detection of norovirus in outbreak specimens. Eur J Clin Microbiol Infect Dis 2005;24:615--8. 11. Thongprachum A. et al. Evaluation of an immunochromatography method for rapid detection of noroviruses in clinical specimens in Thaïland. J Med Virol 2010;82:2106—2109. 12. Liu P, Yuen Y, Hsiao HM, Jaykus LA, Moe C. Effectiveness of liquid soap and hand sanitizer against Norwalk virus on contaminated hands. Appl Environ Microbiol 2010;76:394--9. 13. Johnston CP, Qiu H, Ticehurst JR, et al. Outbreak management and implications of a nosocomial norovirus outbreak. Clin Infect Dis 2007;45:534--40. 14. Rosenthal NA, Lee LE, Vermeulen BA, et al. Epidemiological and genetic characteristics of norovirus outbreaks in long-term care facilities, 2003--2006. Epidemiol Infect 2011; 139:286--94. 15. MacCannell T, Umsheid CA, Agarwal RK, et al. Guideline for the prevention and control of norovirus gastroenteritis outbreaks in healthcare settings. Atlanta, GA: US Department of Health and Human Services, CDC; 2010. 16. CDC. Norovirus in healthcare facilities fact sheet. Atlanta, GA: US Department of Health and Human Services, CDC; 2006. 17. Taranisia MacCannell et al. Guideline for the prevention and control of norovirus gastroenteritis outbreaks in healthcare settings. CDC; 2011. 18. US Environmental Protection Agency. List G: EPA’S Registered Antimicrobial Products Effective Against Norovirus. January 9, 2009. 19. Aron J. Hall et al. Updated norovirus outbreak management and disease prevention guidelines. CDC, MMWR, recommendations and Reports, vol.60, N°3, march 2011. 14 Cat Scratch Disease and Bartonellosis : clinical and diagnostic aspects Dr B. Kabamba-Mukadi, Dr P. Goubau, Dr M. Bodeus and Dr M. Delmée Microbiologie, UCL Av. Hippocrate, 54/92 - 1200 Bruxelles [email protected] Among Bartonella species, B. bacilliformis (Carrion’s disease: Oraya fever and verruga peruana), transmitted by sandflies, and B. quintana (trench fever), transmitted by body lice, are specifically linked to the human host. B. henselae, a cat Bartonella, causes cat scratch disease (CSD) in humans. CSD was described by Debré et al. in 1950, but it was not until 1992 that Rochalimeae henselae was identified, which would become B. henselae. It is a gram negative aerobic bacterium of the genus Proteobacteria and is related to Brucella and Rickettsia. Apart from classical CSD with an inoculation lesion and an adenopathy which may be suppurative, B. henselae may cause bacillary angiomatosis, hepatic peliosis or relapsing fevers in the immunosuppressed. Endocarditis with valvulopathy and bacteraemic fever may be due to B. henselae, but is due more often to B. quintana. Transient articular symptoms, neuroretinitis, organ involvement or multiple adenopathies have been described. Parinaud’s oculo-ganglionic syndrome is a particular presentation due to conjunctival inoculation, with granulomatous conjunctivitis and retro-auricular adenopathy. A definite diagnosis can be obtained on biopsy by histopathology, confirmed by PCR for Bartonella. Biopsy is often performed to exclude a lymphoma or tuberculosis. Serology is mostly performed because it is less invasive. First choice is at present immunofluorescence (IF), with variable sensitivity and specificity. As IF is performed in our laboratory, a titre of 1/640 of the IgG is considered as clearly positive, indicating past or present infection. IgM is only performed on IgG positive samples and a weak titre (1/100) should be considered cautiously. At that level specificity is far from perfect. PCR is the standard and is usually performed on biopsy, but can be done on blood when a bacteraemic form or endocarditis is suspected. We perform sequencing for species identification. We detected essentially B. henselae. Treatment is essentially symptomatic with analgesics if needed, puncture and drainage in purulent forms. Antibiotics have only proven usefulness in generalized or complicated forms. References Edouard S & Raoult D. Bartonella henselae, un agent d’infections ubiquitaires. Médecine et Maladies infectieuses, 40 : 319-330, 2010. Kaiser PO, Riess T, O’Rourke F, Linke D, Kempf VAJ. Bartonella sp. : Throwing light on uncommon human infections. International Journal of Medical Microbiology, 301: 7-15, 2011. 15 16 Group B streptococci, an European perspective with results of the DEVANI project Dr P. Melin Medical Microbiology Laboratory, University Hospital of Liège Sart-Tilman, Bât. 23 - 4000 Liège [email protected] In 2011, neonatal group B streptococcal (GBS) diseases remain a global public health concern. Where consensus guidelines to detect and treat intrapartum women with GBS colonization have been widely adopted, incidence of neonatal early onset disease (EOD) has dramatically declined, however despite preventive strategies cases still occur. The strategy was not expected to prevent all cases and there are challenges and limitations to this preventive approach. The best strategy for European countries is still a matter of debate and intrapartum antimicrobial prophylaxis (IAP) is not widely recommended. To adopt the best preventive strategy, we first need better data assessing more accurately the true burden of GBS diseases in the different countries. Furthermore, as the current screening-based strategy for prevention is highly effective but imperfect, given the challenges, limitations and potential complications of maternal IAP, a new approach is still needed. Maternal immunization against GBS is an attractive alternative for the prevention of not only neonatal diseases but also stillbirths and maternal diseases. Vaccines against GBS may likely become the most effective and sustainable long-term preventive strategy. But the development of vaccines with global relevance has been hampered by changes in the distribution of GBS serotypes of strains causing diseases over time and in different parts of the world. A multivalent vaccine to cover against the more prevalent serotypes suitable for European populations might not be suitable for Asian or African populations. To overcome type-specificity, new developments target vaccines based on conserved surface antigenic proteins, such as Sip protein located at the cell surface of all GBS and on immunogenic proteins from GBS pili. A pilus-based GBS vaccine is appealing and could become a globally relevant reality. The DEVANI (DEsign of a Vaccine Against Neonatal Infections) programme funded through the European Commission Seventh Framework was launched on 1 January 2008 with the key objective being the assessment of European GBS epidemiology to facilitate the design of a new vaccine that will confer neonatal immunity through a durable maternal immune response. A major component was to undertake pan European surveillance of maternal colonisation, maternal GBS antibody responses and neonatal diseases in eight European countries. Through 2009 and 2010, all Belgian laboratories sending any neonatal GBS invasive isolate to the National Reference Centre for GBS were invited to bring their contribution to this project. Belgium, Bulgaria, Czech Republic, Denmark, Germany, Italy, Spain and the United Kingdom established specific GBS screening studies during 2008/10. Maternal vaginal/rectal swabs and sera were taken between 34-37 weeks gestation and processed using a standardised microbiological screening protocol. Samples from neonatal cases were processed using local procedures. For each pregnant woman and each case of GBS neonatal disease, standardized case report forms were filled. GBS isolates were characterised using standardised serological and molecular typing methods for detection of all ten GBS capsular polysaccharide types (Ia to IX). Furthermore all the collected isolates were screened by multiplex PCR and FACS analysis to evaluate respectively gene presence and surface-exposure of pili. And clonal analysis of these isolates was performed using multi-locus sequence typing (MLST). The main microbiological results of this pan European surveillance are following. Carriage rates among pregnant women in all countries ranged from 8% to 26%. The most common GBS capsular types were III (33%), Ia (25%) and V (8%). Among GBS from EOD, the major serotypes were III (43%), V (21%) and Ia (18%). In contrast among GBS isolated from neonatal late onset disease (LOD), serotype III was highly predominant (80.6%) followed mainly by Ia (12.5%). Analysis of the pattern of pili genes showed that all isolates contained at least one gene coding for pili. The most common gene patterns found were PI-2a alone, PI 1+2a and PI 1+2b, while the PI-2b gene alone was very rare. The most prominent result was that a majority of isolates from neonatal infections carried the PI1+2b gene pattern, while the most common pattern among pregnant women was PI-1+2a. Most of analyzed strains express at least one pilus on their surface. The clonal analysis showed that 66 sequence types were found to belong to nine clonal complexes (CC). Among these nine CCs, five were prevailing and covered 92 % of GBS isolates tested. The GBS population in pregnant women was found to be more heterogeneous than the GBS isolated from neonatal infection cases. Among neonatal isolates, the most frequent CC was CC17 (43 %) known as a highly virulent clone. Among participating countries, there were no significant differences in the occurrence of clonal complexes. 17 The analysis of the levels of specific antibodies as surrogate markers of protection is still ongoing. More detailed and additional results as the main conclusions will be presented. Further reading - - DEVANI (DEsign of a Vaccine Against Neonatal Infections) programme funded through the European Commission Seventh Framework: http://www.devaniproject.org Melin, P. Neonatal group B streptococcal disease: from pathogenesis to preventive strategies. (Invited review). Clin Microbiol Infect. 2011 Sep;17(9):1294-303. doi: 10.1111/j.1469-0691.2011.03576.x. Epub 2011 Jun 14. Melin, P. (2009). GBS - Chapître 32. In S., Alexander, F., Debiève, P., Delvoye, C., Kirkpatrick, & V., Masson (Eds.), Guide de Consultation Prénatale (1ère édition). Bruxelles, Belgique: de Boeck. Margarit I, Rinaudo CD, Galeotti CL, Maione D, et al. Preventing bacterial infections with pilus-based vaccines: the group B streptococcus paradigm – J Infect Dis 2009;199:108-115 Centers for Disease Control and Prevention.Prevention of perinatal Group B streptococcal disease. Revised guidelines from CDC, 2010. MMWR 2010;59 (RR-10); 32 pages Van Dyke MK, Phares CR, Lynfield R, et al. – Evaluation of universal antenatal screening for group B streptococcus. N Engl J Med, 2009;360:2626-2636 Verani JR, Schrag SJ – Group B streptococcal disease in infants: progress in prevention and continued challenges. Clin Perinatol, 2010;37:375-392 Poyart C, Reglier-Poupet H, Tazi A, et al. – Invasive Group B streptococcal infections in infants, France. Emerg Infect Dis, 2008;14:1647-1649 18 Waterborne diseases and outbreaks associated with drinking water Dr. K. De Schrijver Vlaamse Gemeenschap - Toezicht Volksgezondheid Lange Kievitstraat, 111-113 Bus 31 - 2018 Antwerpen [email protected] At the beginning of December 2010 the provincial drinking water company of Antwerp was informed of faecal contamination of tapwater in two villages in the province of Antwerp. To measure the impact of the incident case finding was organised among the patients of the general practitioners of the two villages. Via a retrospective descriptive survey conducted among 1000 households, chosen at random out of the 18,300 inhabitants of the two villages, the gastrointestinal symptoms in the population were registered and the association with drinking water was tested. Stools and drinking water samples were tested for gastrointestinal pathogens. Via case finding, 603 patients were identified and six out of them were admitted to hospital. Out of the 1000 households 1,185 persons (52.5%) responded the inquiry and 224 (18.4%) met the criteria of an outbreak case. Out of the 1,185 people 176 (15.2%) had mild or late symptoms. Out of the 75 stools specimens from symptomatic patients 26 (34%) were positive for gastrointestinal pathogens. Tapwater was highly positive for faecal bacteria. Drinking tap water and contracting gastroenteritis was significantly associated (RR = 3.38; 95% CI 2.6 – 4.3). The more the patients had drunk from the water, the higher the risk for gastroenteritis (P < 0.001). The zone in which the people lived was associated with an increased risk for gastro-enteritis (RR = 1.37; 95% CI 1.1 – 1.7). The analysis of the drinking water, which included a chemical and a microbiological comparison of contaminated drinking water and the river water used for fire works, revealed that most probably an important amount of river water was pumped inside the canalisation system during the fire works at 6 December 2010. Literatuurreferenties 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. Leclerc H, Schwartzbrod L, Dei-Cas E. Microbial agents associated with waterborne diseases. Crit Rev Microbiol. 2002; 28(4): 371-409. Fernandes TMA, Schout CS, de Roda-Husman AM, Eilander A, Vennema H, van Duynhoven YTHP. Gastroenteritis associated with accidental contamination of drinking water with partially treated water. Epidemiol Infect. 2007; 135: 818-26. Hunter PR, Syed Q. A community survey of self reported gastroenteritis undertaken during an outbreak of cryptosporidiosis strongly associated with drinking water after much press interest. Epidemiol Infect. 2002; 128: 433-8. Laine J, Huovinen E, Virtanen MJ, Snellman M, Lumio J, Ruutu P, et al. An extensive gastroenteritis outbreak after drinking-water contamination by sewage effluent, Finland. Epidemiol Infect. 2010; 15: 19. Gallay A, De VH, Cournot M, Ladeuil B, Hemery C, Castor C, Bon F, Megraud F, et al. A large multipathogen waterborne community outbreak linked to faecal contamination of a groundwater system, France, 2000. Clin Microbiol Infect. 2006; 12(6): 561-70. Clark CG, Price L, Ahmed R, Woodward DL, Melito PL, Rodgers FG, et al. Characterization of waterborne outbreak-associated Campylobacter jejuni, Walkerton, Ontario. Emerg Infect Dis. 2003; 9(10): 1232-41. Smith A, Reacher M, Smerdon W, Adak GK, Nichols G, Chalmers RM. Outbreaks of waterborne infectious intestinal disease in England and Wales, 1992-2003. Epidemiol Infect. 2006; 134(6): 11419. Mac Kenzie WR, Hoxie NJ, Proctor ME, Gradus MS, Blair KA, Peterson DE, Kazmierczak JJ, Addiss DG, Fox KR, Rose JB. A massive outbreak in Milwaukee of Cryptosporidium infection transmitted through the public water supply. N Engl J Med. 1994; 21(3): 161-7. De Schrijver K. Groepinfecties. In: Richtlijnen Infectieziektebestrijding Vlaanderen Editie 2011. Eds.: De Schrijver K, Flipse W, Laisnez V, Mak R, Steenbergen JE van, Timen A, Beaujean DMJA (Red). Bilthoven: RIVM-CIB, LCI-Vlaams Agentschap Zorg en Gezondheid 2011: 9-87. CDC. EpiInfo 3.5.3 2011. Belgisch staatsblad 28 januari 2003. Besluit van de Vlaamse regering van 13 december 2002 houdende reglementering inzake de kwaliteit en levering van water, bestemd voor menselijke consumptie. PIDPA. Watercycle Research Institute. Intern verslag Drinkwatercontaminatie Schelle Hemiksem december 2010. Antwerpen 2011. Guerrant R, Steiner TE. Principles and syndromes of enteric infection. In: Mandell, Douglas and th Bennett’s Principles and Practice of Infectious Diseases. 6 Ed. Eds: G Mandell, JE Bennett, R Dolin. Philadelphia: Elsevier Churchill Livingstone 2005: 1215-310. De Schrijver K, Vanwanrooy S. Maagdarminfecties na drinkwaterverontreiniging. Vlaams Infectieziektebulletin ingediend 2011. 19 15. 16. Rasanen S, Lappalainen S, Kaikkonen S, Hamalainen M, Salminen M, Vesikari T. Mixed viral infections causing acute gastroenteritis in children in a waterborne outbreak. Epidemiol Infect. 2010; 138(9): 1227-34. Craun GF, Brunkard JM, Yoder JS, Roberts VA, Carpenter J, Wade T, Calderon RL, Roberts JM, Beach MJ, Roy SL. Causes of outbreaks associated with drinking water in the United States from 1971 to 2006. Clin Microbiol Rev. 2010; 23(3): 507-28. 20 Infectious diseases in the elderly Dr. J. Flamaing Department of Geriatric Medicine University Hospitals Herestraat, 49 – 3000 Leuven [email protected] Life expectancy is rising in Belgium and Belgian citizens live longer in good health than before. The only age group that will show a growth is the age group above 65 years. In 2050 20 % of the population will be older than 65 y. The number of centenarians will rise 8 fold by 2050. One of two women born now will reach the age of 100. Geriatric medicine treats older persons charactarised by frailty and multiple comorbidities and the pluridisciplinary geriatric approach results in an improved survival, better function and cognition and less institutionalization compared to standard in-hospital care. The incidence of several infections (LRTI, UTI, SSTI) rises with age in adults and mortality from infections is the highest in the oldest age group. Physiological aging, aging of the immune system, frailty, comorbidities and the environment result in the susceptibility for infections of older persons. The clinical presentation of infections in older people is atypical. Typical symptoms of infection (fever and localizing symptoms) are less and geriatric syndromes (delirium, falls, functional decline,…) more prevalent. Diagnosis of the infection is more difficult in older persons and can result in delay of therapy and thereby in increased morbidity and mortality. Obtaining adequate samples for microbiology is more difficult in older persons and can lead to under- and misdiagnosis. The patogens responsible for infections in older people depend on the setting (community, residential, hospital), the history (previous AB use) and the profile (functionality, frailty, comorbidity) of the older person. Multidrug resistant pathogens are more frequent causes of infection in older, dependent patients with a history of recent antibiotic use. The empirical choice of AB therapy in older patients is hampered by polypharmacy, intolerance and need for dose adjustment caused by diminished renal clearance. Prevention strategies for infections are important in older persons. Vaccines (TIV, 23PPV and dT(p)) need to be administered in all persons ≥ 65 y. The vaccination of health care workers (TIV) and contacts (mainly small children, PCV13) of older persons with comorbidity and immunosenescence) can passively protect this vulnerable population by herd immunity. Infectious diseases in older people is a challenging and evolving field. Every health care worker dealing with adults will be confronted with older patients and infections. References • • • Immunosenescence: Implications for vaccination programmes in adults. Lang PO, Govind S, Michel JP, Aspinall R, Mitchell WA. Maturitas 2011; 68:322-30. Updated vaccine guidelines for aging and aged citizens of Europe. Michel JP. Expert Rev Vaccines 2010; 9:7-10. Epidemiology and unique aspects of aging and infectious diseases. Yoshikawa TT. Clin Infect Dis 2000; 30:931-3. 21 22 Diagnostic criteria for invasive mycoses Dr. D. Vogelaers UZ Gent De pintelaan, 185 - 9000 Gent [email protected] 23 24 D/2011/2505/40 25