Przegląd Epidemiologiczny Epidemiological Review

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1 Przegląd Epidemiologiczny Epidemiological Review QUARTERLY JOURNAL OF THE NATIONAL INSTITUTE OF PUBLIC HEALTH NATIONAL INSTITUTE OF HYGIENE AND THE POLISH SOCIETY OF EPIDEMIOLOGY AND INFECTIOUS DISEASES Index Copernicus 9 MNiSW 7pkt VOLUME No 4 CONTENTS Full text: EDITORIALS A Zieliński: Diet and cancer risk/association between diet and risk of cancer M Wróbel-Harmas, M Krysińska, J Postupolski, M J Wysocki: Food supplement related risks in the light of Internet and RASFF data PROBLEMS OF INFECTIONS J E Drozd-Sokołowska, G Dulny, A Waszczuk-Gajda, W W Jędrzejczak: An isolated outbreak of influenza A H1N1 in a Haematological Department during post-pandemic period K W Pancer, W Gut, E Abramczuk, B Lipka, B Litwińska: Non-influenza viruses in acute respiratory infections among young children, high prevalence of HMPV during the H1N1V pandemic in Poland K Piekarska, M Rzeczkowska, W Rastawicki, A Dąbrowska-Iwanicka, I Paradowska-Stankiewicz: Usefulness of laboratory methods in diagnosis of pertussis in adult with paroxysmal cough T M Zielonka: Risk factors of tuberculosis and specific manifestations of disease L Kępa, B Oczko-Grzesik, A Boroń-Kaczmarska: Cerebrospinal fluid interleukin-6 concentration in patients with purulent, bacterial meningitis - own observations K W Pancer, M T Szkoda, W Gut: Imported cases of dengue in Poland and their diagnosis P Kajfasz, M Bartoszcze, P K Borkowski, W Basiak: Retrospective review of the case of cutaneous anthrax malignant pustule from 1995 in 15-year old girl Z Wolak, M Z Wałaszek, W Dobroś, M J Wałaszek, B Jagiencarz-Starzec: Prevalence of gastrointestinal system infections acquired in provincial hospital in A Schneider, A Mól, K Lisowska, M Jax-Dambek, D Lachowicz, P Obuch-Woszczatyński, H Pituch: Three-step diagnostic algorithm in diagnosing patients suspected of Clostridium difficile associated diarrhea PUBLIC HEALTH M Krzyżak, D Maślach, K Piotrowska, A E Charkiewicz, A Szpak, J Karczewski: Perinatal mortality in urban and rural areas in Poland in

2 K Dudek: Impact of biodiversity on tick-borne diseases J Kluz-Zawadzka, A Hartmann-Ksycińska, B Lewandowski: Emergent management of scorpion sting I Strużycka, E Rusyan, A Bogusławska-Kapałą: Prevalence of dental erosion in young adults aged 18 years in Poland HISTORY OF MEDICINE M Gromulska: Ludwik Hirszfeld in National Institute of Hygiene in REPORTS Coordination of public institution response to a threat epidemic. Workshop held in the National Institute of Public Health National Institute of Hygiene on 11 st September List of reviwers INSTRUCTION FOR AUTHORS 707 Contents vol. 68 (insert)

3 ARTICLES IN POLISH Przegląd Epidemiologiczny Epidemiological Review K W A R T A L N I K NARODOWEGO INSTYTUTU ZDROWIA PUBLICZNEGO PAŃSTWOWEGO ZAKŁADU HIGIENY I POLSKIEGO TOWARZYSTWA EPIDEMIOLOGÓW I LEKARZY CHORÓB ZAKAŹNYCH Index Copernicus 9 Punktacja MNiSW 7 TOM NR 4 TREŚĆ Pełne teksty: ARTYKUŁY REDAKCYJNE A Zieliński: Dieta a czynniki ryzyka nowotworów M Wróbel-Harmas, M Krysińska, J Postupolski, M J Wysocki: Zagrożenia związane ze stosowaniem suplementów diety w świetle analizy danych z Internetu i systemu RASFF PROBLEMY ZAKAŻEŃ J E Drozd-Sokołowska, G Dulny, A Waszczuk-Gajda, W W Jędrzejczak: Ognisko epidemiczne grypy A H1N1 w oddziale hematologii po zakończonej pandemii K W Pancer, W Gut, E Abramczuk, B Lipka, B Litwińska: Czynniki wirusowe ostrych zakażeń dróg oddechowych u małych dzieci. Wzrost zachorowań wywołanych przez metapneumowirusy podczas pandemii grypy 2009 w Polsce K Piekarska, M Rzeczkowska, W Rastawicki, A Dąbrowska-Iwanicka, I Paradowska-Stankiewicz: Przydatność diagnostyki mikrobiologicznej w rozpoznaniu krztuśca u osoby dorosłej z napadowym kaszlem T M Zielonka: Czynniki ryzyka gruźlicy i szczególne postacie choroby L Kępa, B Oczko-Grzesik, A Boroń-Kaczmarska: Stężenie interleukiny-6 (IL-6) w płynie mózgowo- -rdzeniowym chorych z ropnymi, bakteryjnymi zapaleniami opon i mózgu obserwacje własne K Pancer, M T Szkoda, W Gut: Zawleczenia zakażeń wirusem denga w Polsce i ich rozpoznanie P Kajfasz, M Bartoszcze, P K Borkowski, W Basiak: Retrospektywne omówienie przypadku skórnego wąglika czarnej krosty z 1995 roku u 15-letniej dziewczynki Z Wolak, M Z Wałaszek, W Dobroś, M J Wałaszek, B Jagiencarz-Starzec: Występowanie szpitalnych zakażeń przewodu pokarmowego w latach w szpitalu wojewódzkim A Schneider, A Mól, K Lisowska, M Jax-Dambek, D Lachowicz, P Obuch-Woszczatyńsaki, H Pituch: Zastosowanie trójstopniowego algorytmu w diagnostyce pacjentów z podejrzeniem biegunki poantybiotykowej o etiologii Clostridium difficile hospitalizowanych w szpitalu klinicznym im.przemienienia Pańskiego Uniwersytetu Medycznego w Poznaniu

4 ZDROWIE PUBLICZNE M Krzyżak, D Maślach, K Piotrowska, A E Charkiewicz, A Szpak, J Karczewski: Umieralność okołoporodowa noworodków w mieście i na wsi w Polsce w latach K Dudek: Wpływ poziomu bioróżnorodności na zagrożenie chorobami odkleszczowymi J Kluz-Zawadzka, A Hartman-Ksycińska, B Lewandowski: Postępowanie ratownicze po ukłuciu skorpiona I Strużycka, E Rusyan, A Bogusławska-Kapała: Występowanie erozji szkliwa w populacji młodych dorosłych w wieku 18 lat w Polsce HISTORIA MEDYCYNY Ludwik Hirszfeld w Państwowym Zakładzie Higieny w latach SPRAWOZDANIA Koordynacja działań instytucji publicznych w przypadku zagrożenia epidemią. Konferencja w Narodowym Instytucie Zdrowia Publicznego PZH w dniu 11 września 2014 roku Materiały przygotowane na Konferencję przez Ministerstwo Zdrowia: Gorączka krwotoczna Ebola definicja przypadku (zaadaptowana do krajowego nadzoru epidemiologicznego). Wersja definicji przypadku z dnia 09 września 2014 Algorytm diagnostyczny EVD z ECDC wersja PL z dnia Interpretacja wybranych elementów algorytmu postępowania w zakresie prowadzenia laboratoryjnej diagnostyki pacjentów podejrzanych o zakażenie wirusem Ebola (dotyczy osób z objawami klinicznymi, które spełniają kryteria definicji przypadku EVD) Gorączka Ebola informacja dla lekarzy POZ i służb medycznych Załącznik A. Szczegółowe zalecenia w zakresie środków ochrony osobistej do stosowania w kontakcie z podejrzanymi lub chorymi na EVD i zwłokami Ministerstwo Zdrowia: Osoba powracająca z krajów Afryki Zachodniej, gdzie odnotowano przypadki goraczki krwotocznej Ebola Spis recenzentów INSTRUKCJA DLA AUTORÓW 799 Spis tomu 68 (wkładka)

5 PRZEGL EPIDEMIOL 2014; 68: Editorials Andrzej Zieliński DIET AND CANCER RISK/ ASSOCIATION BETWEEN DIET AND RISK OF CANCER Department of Epidemiology, National Institute of Public Health-National Institute of Hygiene ABSTRACT The article discusses problem of the association between diet and risk of cancer. Author shows methodological concerns arising from the difficulty of selecting the study groups, and also those dependent on ascertainment of the composition of the diet for a long period of time necessary to establish the statistical associations. Sources of carcinogenic substances in food include environmental contaminants, chemicals synthesized in some plants and those which infiltrate the food or are produced during the food processing. It is strongly advisable to limit the content of carcinogenic substances in food by imposing Regulation (EC) No 1881/2006 not only regarding products exported to the EU countries, but also those intended for local market. Key words: carcinogens, diet, individual risk, societal risk INTRODUCTION Studies aimed at identifying risk factors of cancer represent a serious challenge for epidemiologists. Firstly, it is affected by a multitude of potential factors as well as their coexistence in various combinations. Furthermore, their effects may be observed many years following repeated exposure. Generally, exposure assessment is an approachable task if exposed population and exposure level are easy or at least feasible to define. Examples of such exposures may be: contact with tobacco smoke or working with asbestos. Having considered the exposure associated with diet, the situation is even more problematic for researchers. The first problem is that everyone is exposed to eating. Selection of an unexposed population is rarely possible and may be applied to rather limited proportion of meals. Possible assignation of diet composition, both in retrospective and prospective studies, is usually restricted to a slight extent. Interval between exposure to carcinogenic substances and cancer occurrence amounts frequently to many years. In this period, persons may often modify their diet with respect to its quantity and quality. Furthermore, meals may include substances which increase as well as decrease the risk of cancer. In such conditions, not only an attempt to correlate diet with cancer but even to reconstruct diet raise difficulties due to poor recollection of meals eaten over years and the fact that respondents are not entirely aware of the ingredients of meals consumed even at the time of eating. What are the prerequisites for a researcher to determine the relation between diet and cancer? How to link diet composition with cancer? Even in the countries where there is a high prevalence of cancer, individual risk is relatively low. Cohort studies would require a large number of study participants and long-term observation period accompanied by difficult and unreliable verification of exposure resulted from meals consumed. Another difficulty consists in selecting control group. Having considered a high prevalence of exposure with the example being consumption of meat products, control group selected from vegetarians could differ considerably from study group in terms of eating habits and other characteristics. Consequently, selection of one particular variable to the analysis would raise many reservations of methodological nature. However, there are data which indirectly suggest the relation between the prevalence of cancer in a particular population and eating habits being typical of this population. Namely, various populations living in different geographical areas and having diverse eating habits show rather considerable disparities in the distribution of cancer types. Such relations should not be considered as evidence due to possible ecological fallacy occurrence. In population where there is a National Institute of Public Health National Institute of Hygiene

6 610 Andrzej Zieliński No 4 high prevalence of exposure and disease, exposure is not necessarily restricted to persons who contracted a disease. Having considered initial data, however, it is much easier to investigate this individual relation in case-control studies where not the consumption of a particular meal but its estimated intake is considered to be a variable. Even if we assume that knowledge obtained is of limited probability, recommendations and preventive measures should always stand on the side of prevention of diseases, not the food industry interests. Nevertheless, there is a counter-argument which should not be neglected. Persons have the right to use all existing doubts to be on a diet which is harmful for them. An example could be tobacco smoking. Impact of smoking on developing cancers and coronary heart diseases is well documented. There are no legal or moral basis, however, for forbidding an adult to smoke. At the most, it is possible to promote anti-smoking measures and forbid smoking in places where tobacco smoke may affect non-smokers. Similarly, food which includes high concentration of substances whose carcinogenic properties have been established with high probability should be adequately labeled as posing a threat for developing a cancer. Such meals, on no account, should be served to children. CANCER RISK ATTRIBUTED TO DIET From public health perspective, the basic division of risk factors for diseases refers to the prevention of diseases by their elimination or reduction of their impact. A list of factors which are not modifiable include: genetics and age-dependent factors while risk factors for developing cancers such as chemical substances included in food may and should be eliminated from a diet. In some cases, however, it is very difficult (1). Chemical substances of carcinogenic properties may be present in food if environment or the surfaces of vegetables or livestock feed were contaminated. In the majority of cases, mechanical contamination may be removed while cleaning fruits and vegetables. As in case of metal ions, penetration of many organic carcinogenic substances, including polycyclic aromatic hydrocarbons (PAH) to the inner tissues of vegetables, especially roots and bulbs is observed irrespective of the existing biological barriers (2). Environmental effects of contamination on cancer are hard to assess, excluding high-contaminated areas. Consequently, they are of little significance as individual risk factors of cancer. Even in low-contaminated areas, however, their effect on local population should be considered (3). Some of this substances are synthesized in edible plants, however, their low concentrations do not pose any threat to humans (4). Furthermore, some plants contain substances which may inhibit the development of some forms of cancer, including organic sulphur compounds, flavonoids, tannins and carotenoids. They are present in some fruits and cruciferous vegetables such as broccoli or cauliflower. Their concentrations, however, are not enough to state that the consumption of these vegetables and fruits is of anticancer effect (5). The most serious threats are attributed to preparation of meat meals at high temperatures, especially during food grilling or smoking (4). Since a number of years, smoking of food is becoming more and more popular in Poland. Usually, it is affected by customs, technicalities of professional or homemade food smoking equipment. Supervision of sanitary institutions, however, is not sufficient enough in this respect. Grilling is a custom which gained greater recognition in the last decades. Its popularity is still on the increase. Grilled meat, its products and fish are served during outdoor meetings. Yet, both heat and smoke trigger formation of substances of confirmed carcinogenic properties in meat, including polycyclic aromatic hydrocarbons (6). Neither the Ministry of Health nor the Polish sanitary institutions responded adequately to a triumphant tone of politicians who secured derogation of Polish traditionally smoked meat and meat products for local production and consumption from the provisions of the Regulation (EC) No 1881/2006 regarding maximum levels of polycyclic aromatic hydrocarbons in traditionally smoked meat and meat products. Furthermore, no Polish maximum levels of PAH for meat products intended for local production and consumption were introduced which may be interpreted that there is a discretion in smoking techniques which consequently may lead to risky PAH concentration. For non-smokers, diet and physical activity are basic modifiers of risk of internal organ cancers. Their occurrence is dependent on individual health behaviours. Therefore, it is an important domain of health promotion. If polycyclic aromatic hydrocarbon concentrations in meat products are subject to EC regulations, and they should be also regulated by Polish law, then the amount of carcinogenic substances contained in meals is associated with the frequency and quantity of their intake. According to the American Cancer Society, obesity per se increases the risk of occurrence of many forms of cancer, including breast cancer in postmenopausal women, colorectal cancer, renal cell cancer, esophageal cancer, pancreatic cancer, endometrial cancer, thyroid cancer and gallbladder cancer. Furthermore, association between other forms of cancer was also established, however, it is not of statistical significance. Nearly 1/3 of cancers in the United States are potentially attributed

7 No 4 Diet and cancer risk 611 to obesity. Moreover, not only obesity in adulthood increases the risk of cancer but also high birth weight. Stable and sustained weight loss decreases the probability of cancer while cyclic weight loss and gain is a risk factor of cancer. Obesity affect the risk of cancer via mechanisms such as levels and modifications of hormone effects and activity of factors such as interleukins subsequent to immune and inflammatory reactions (7). CONCLUSIONS 1. In health promotion and cancer prevention activities, factors associated with diet are not given sufficient attention compared to their importance. Beside tobacco smoking prevention, they represent the most important domain of practically free of charge preventive measures. 2. It is of importance to raise the awareness of authorities and politics on the liability for introduction of regulation regarding the launch of products containing low concentrations of substances of confirmed carcinogenic properties intended for local consumption. 3. Promotion of healthy eating should cover the strategy of tackling obesity with regard to the prevention of type 2 diabetes, coronary heart diseases as well as cancer. REFERENCES 1. US Department of Health and Human Services. National Institutes of Health. List of Cancer-Causing Agents Grows. htm 2. A.M. Kipopoulou, E. Manoli, C. Samara. Bioconcentration of polycyclic aromatic hydrocarbons in vegetables grown in an industrial area. Environmental Pollution 1999;106 (3): Nyberg F, Boffetta P. Contribution of environmental factors to cancer risk. Br Med Bull 2003; 68 (1): Polycyclic Aromatic Hydrocarbons in Cereals, Cereal Products, Vegetables, and Traditionally Smoked Foods. Food Survey Information Sheet; Number 01/12 April 2012, Food Standards Agency (food.gov.uk) multimedia.food.gov.uk/multimedia/pdfs/poly-aromatic- -hydrocarbons.pdf 5. National Cancer Institute (NIH). Cruciferous Vegetables and Cancer Prevention 6. National Cancer Institute (NIH). Chemicals in Meat Cooked at High Temperatures and Cancer Risk. cancer.gov/cancertopics/factsheet/risk/cooked-meats 7. Kushi LH, Doyle C, Cullough M et al. American Cancer Society Guidelines on Nutrition and Physical Activity for Cancer Prevention Reducing the Risk of Cancer With Healthy Food Choices and Physical Activity. onlinelibrary.wiley.com/doi/ /caac.20140/pdf Received: Accepted for publication: Address for correspondence: Prof. Andrzej Zieliński Department of Epidemiology National Institute of Public Health-National Institute of Hygiene Chocimska 24, Warsaw tel azielinski@pzh.gov.pl

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9 PRZEGL EPIDEMIOL 2014; 68: Editorials Monika Wróbel-Harmas 1, Magdalena Krysińska 2, Jacek Postupolski 3, Mirosław J. Wysocki 4 FOOD SUPPLEMENT RELATED RISKS IN THE LIGHT OF INTERNET AND RASFF DATA 1 Department of Social Communication and Marketing 2 Department of Organization, Health Economics and Hospital Management 3 Department of Food Safety 4 Department of Health Promotion and Postgraduate Education National Institute of Public Health National Institute of Hygiene ABSTRACT OBJECTIVE. Based on legal acts and RASFF information, this paper aimed at evaluating available facts on food supplements in comparison to the most popular data accessible via Internet for future and present consumers. MATERIAL AND METHODS. Having analyzed legal acts and RASFF (Rapid Alert System for Food and Feed) database, the authors attempted to verify what kind of information on food supplements may be found by an Internet user, using the first webpage of Google.pl. This search engine was used in this study as it gained the highest popularity among Internet users. It was decided that exclusively search results displayed on the first webpage would be subject to analysis as 91.5% of Internet users limit their search to the first 9-10 results. Internet was searched using the following two terms: supplement and supplements as well as terms suggested by Google. pl. Subsequently, the results were subject to qualitative and quantitative analyses. RESULTS. On the Internet, the most frequently searched terms were: supplements ( ), supplement ( ), supplements shop ( ). Having analyzed the content of particular websites, information on certain products, given by their manufacturers may be found. Then, data on supplement itself were provided, i.e. what is a supplement and when it should be used. Expert articles (written by physicians, dieticians, pharmacists) on a risk resulting from these products, including therapeutic indications or the presence of unauthorized substances were identified considerably less frequently. No warnings regarding the necessity of purchasing the products in legal and verified places were found. CONCLUSIONS. There is a necessity of systemic education of consumers on reasonable use of food supplements. It is also advisable to consider the organization of alert system whose objective would be to monitor adverse reactions caused by an intake of food supplements or novel food launched into the country. To obtain reliable information on the composition and effects of food supplements, potential consumer should contact physician or dietician. Additionally, complementary information, using different sources with an example being health-related portals, presenting articles written by physicians or pharmacists, may be also searched. Key words: food supplements, food supplement use, food supplement effect INTRODUCTION Food supplements are becoming more popular. Furthermore, they are also more accessible. It may be purchased not only in a grocery, which seems to correspond to its definition, but also in chemist s, gym, but above all on the Internet. Having analyzed the advertisements, it may be concluded that these products cure all of the possible conditions, ranging from hair loss, potency problems to the quick loss of unwanted kilograms. Manufacturers eagerly inform of the lack of adverse reactions to supplement and its natural origin. Additionally, launching new products into a market is accompanied by aggressive marketing and advertising campaigns. Consequently, consumers may consider that if they are concerned about their health, they should increase the intake of supplements. Therefore, it is high time for reflection on dietetic and medical reasons of such high consumption of food supplements. National Institute of Public Health National Institute of Hygiene

10 614 Monika Wróbel-Harmas, Magdalena Krysińska, et al. No 4 Except for certain physiological conditions, e.g. immunodeficiency or pregnancy, the intake of food supplements is not recommended if the principles of healthy diet are observed. An emphasis should be put on the fact that the composition of supplement may be different from what is on its label. Furthermore, it may contain hazardous substances. From the study conducted in the USA transpires that 20-90% of patients diagnosed with cancer use food supplements, however, their intake is not always approved by physicians. Not only the shortage of evidence suggesting the effectiveness of supplements, but also their questionable safety and possible interactions with medicinal products are raised. In this respect, a key element is good contact between patient and physician. It is also advisable to develop the guidelines for patients regarding the use of food supplements (1). LEGAL ACTS PROTECTING THE CONSUMERS FROM THE RISK OF UNLIMITED ACCESS TO FOOD SUPPLEMENTS Pursuant to the provisions of the Directive 2002/46/ EC on the approximation of the laws of the Member States relating to food supplements, food supplement is defined as any food the purpose of which is to supplement the normal diet and which is a concentrated source of vitamins or minerals or other substances with a nutritional or physiological effect, alone or in combination, marketed in dose form (2). Definition of foodstuff, which is specified in the Regulation (EC) No 178/2002 of the European Parliament and of the Council of 28 January 2002, is as follows: food (or foodstuff) means any substance or product, whether processed, partially processed or unprocessed, intended to be, or reasonably expected to be ingested by humans (3). Composition of food supplements, most frequently, includes vitamins, mineral substances, as well as plantor animal-derived ingredients, which are present in food and consumed as its part. In this case, provisions, referring to medical devices, are not effective. In Poland, the basic legal acts, regulating the launch of food supplements into the market, are the Act on Food and Nutrition Safety (4) and Regulation of the Minister of Health on the composition and labelling of food supplements (5). Chief Sanitary Inspectorate (CSI) is an institution which is liable for registering food supplements in Poland. CSI is also obliged to run the register of food supplements. If a food supplement is to be launched into the market, the entity introducing it should first submit a notification form to the CSI. Such form should contain the following information, i.e. the names of a supplement and notifying entity, label in Polish language and addressee of the first notification. All required documents are accessible on the CSI website (6). Prior to the launch of food supplement, investigation procedure is initiated by the CSI to verify whether a supplement meets the criteria specified in the provisions of law as well as to determine if it does not have properties indicative of medicinal products. In the latter, such product is subject to other provisions of law and is not to be considered as a foodstuff. It should be noted, however, that prior to the launch of a food supplement, its manufacturer is not required to present and accomplish detailed and expensive registration procedures and clinical trials which could confirm its effectiveness, quality and safety profile as it is in the case of medicinal products. Furthermore, manufacturer is not also obliged to inform on interactions with other substances, alcohol and medicinal products. Nevertheless, pursuant to the article 30 of the Act on Food and Nutrition Safety (4), for food supplements, containing vitamins, minerals or other substances with a nutritional or physiological effect, the CSI may initiate investigation procedures to verify the composition, properties of particular excipients and indications for use prior to the launch of product. In case of food supplements, a special attention should be paid to the information provided for consumers. The majority of food supplements is labelled and advertised using nutrition and health claims. Pursuant to the provisions of the Regulation on nutrition and health claims made on foods (7) nutrition claim is defined as any claim which states, suggests or implies that a food has particular beneficial nutritional properties ; health claim means any claim that states, suggests or implies that a relationship exists between a food category, a food or one of its constituents and health while reduction of disease risk claim denotes any health claim that states, suggests or implies that the consumption of a food category, a food or one of its constituents significantly reduces a risk factor in the development of a human disease. Manufacturers cannot arbitrarily place such information on product s packaging or use them in advertisements. It is allowed to use exclusively nutrition claims, which are specified in the register of nutrition claims, constituting an annex to aforesaid regulation. Having received a positive opinion of the European Food Safety Authority (EFSA), which is based on scientific evidence provided by manufacturer and confirms that the claims made are truthful, the European Commission should include a claim in the register. Health claims may be used if the following information is provided: a statement suggesting the significance of balanced diet and healthy lifestyle; food quantity or its pattern of consumption ensuring beneficial effect specified in a claim; a statement for persons who should

11 No 4 Food supplement related risks in the light of Internet 615 refrain from consuming particular food, if deemed appropriate and adequate warning in case of products which can be hazardous to health if consumed excessively. It is not permitted to use claims which suggest that health may be affected if certain products are not consumed. It is also prohibited to use claims referring to the pace or level of weight loss as well as those making reference to the recommendations of particular physicians, health professionals or associations, different from the ones listed in the aforesaid regulation. In the light of increasing supply of food supplements on the local market (8), it is a liability of manufacturers to provide consumers with reliable and comprehensive information on the effect and purpose of products offered. In fact, consumers have to analyze the information on food supplements and investigate the market on their own as to purchase appropriate products of authorized composition and controlled origin. In Poland, the Cluster of Vegetable Medicinal Products and Food Supplements was constituted by the National Medicines Institute to grant Quality Certification. According to the regulation, accessible on the website - (9): The objective of Quality Certification granting is to promote products of documented, scientifically confirmed quality and safety profile, mainly to allow consumers to identify them on the market by using Quality Certification Mark. SAFETY PROFILE OF FOOD SUPPLEMENTS UNDER RASFF To eliminate the sources of risk associated with the consumption of food potentially hazardous to human health, the European Union introduced the Rapid Alert System for Food and Feed (RASFF) (10) whose objective is to protect consumers from the risk of diseases. Since 1978, this system allows for the exchange of information in the EU. Having become an important element of public health protection policy, it consists in collecting and rapid communicating the information on foodstuffs, materials and devices designed for contact with food and feed which could be harmful for the health of consumers. Within the Rapid Alert System for Food and Feed (RASFF), there are three types of notifications, i.e.: alert notification notification on a risk which requires or may require rapid actions undertaken by other members of the RASFF; information notification - notification on a risk which does not require rapid actions. Information notification may be sent with regard to a product for which a serious risk has been identified, however, it is available only on a local market, on a limited territory, or it was not launched into a market or it is no longer present on a market. border rejection. Furthermore, any information which has not been sent as alert, information or border rejection notifications, but is considered to be important for the safety of food and feed, is communicated as News. Within the frames of RASFF, a risk to human health, resulting from the appearance of food, feed, materials and devices for contact with food, which could be harmful for both human health and environment, is assessed. Regulation (EC) No 178/2002 of the European Parliament and of the Council of 28 January 2002 stipulates the criteria for the notification of risk to human health deriving from food or feed (3). According to the provisions of this Regulation, the Member States immediately notify the Commission, under the rapid alert system, of any actions undertaken to limit the launch into the market or to recall the food and feed to protect human health and requiring rapid action as well as any rejections related to a risk to human health, food and feed at a border of the European Union. Notifications should include the events of a direct or indirect risk to human health. RASFF does not cover events in which there is no direct or indirect risk to human health. It should be interpreted that in case of inconsistencies with the law regarding food safety, it is not required to communicate other Member States. As it was stated earlier, the fact whether there is a risk for human or not should be considered as a decisive factor. Having analyzed the provisions of law on food supplements and RASFF data, it should not be forgotten that irrespective of the fact that such information is accessible on the Internet for anyone, exclusively professionals are familiar with it. Furthermore, based on these data, only professionals can draw appropriate conclusions. Therefore, the authors decided to verify what kind of information on food supplements may be found by consumer, using the first webpage of Google. pl (11). MATERIAL AND METHODS Analysis of information, which can be found on the Internet, was performed on September Due to its popularity, Google.pl was employed for analysis (11). It was decided to analyze exclusively search results displayed on the first webpage, i.e. about 9-10 results. It is dictated by the fact that 91.5% of persons limit their search to the first webpage. Only 4.8% Internet users look for the results on the next web pages (12). Two search terms were entered into Google.pl, i.e. supplement and supplements. The only difference is the usage of grammatical number - singular versus

12 616 Monika Wróbel-Harmas, Magdalena Krysińska, et al. No 4 plural. Subsequently, all the results (portals) were investigated with regard to the information on supplements. Results, similar to supplement/supplements, suggested by Google.pl were also analyzed. Additionally, the number of results for particular search terms was examined. No results, marked as advertisements, were subject to analysis. RESULTS Having analyzed the search terms supplement and supplements, and then those suggested by Google.pl, no terms regarding sexual potency/erection occurred. From table I transpires that these terms are on the last position. Internet users were mostly interested in supplements for weight loss and shops with supplements. Table. I Number of search results by search term. No. Search term entered into Google.pl Approximate number of results 1. Supplements Supplement Supplements shop Supplements for weight loss Food supplement Supplements for muscle building Supplements for sexual potency Food supplements Supplements for erection Figure 1 presents the results of search. The first search term was supplement. Search results that were displayed as first related to a supplement meaning a separate section added to a publication. The next term displayed was food supplement. As many as 3 out of 10 results applied for food supplements. Fig.1 Percentage of search results concerning food supplements (search term - supplement ). Having analyzed information on supplements accessible on websites, it may be concluded that these are products used to complement everyday diet by lacking nutrients, including i.a. vitamins or minerals. These products, however, should not be considered as medicinal products, but foodstuffs. Nevertheless, the fact that they may be purchased in chemist s gives an impression that these are medicinal products. From the survey conducted by the Centre for Public Opinion Research TNS OBOP Self-healing through awareness in Poland transpires that 41% of respondents consider supplements to have therapeutic properties (13). There are also products being on the borderline of definition of medicinal product and food (14). During the search, the website of the association the Polish Council for Supplements and Nutritional Foods (KRSiO) was also displayed. This association was instituted to act for the adjustment of legal regulations, assist in the researches on food supplements and other activities protecting the interests of associated manufacturers as well as to provide reliable information for consumers. Manufacturers being the members of the KRSiO were also listed (15). Information suggesting that supplements are to complement normal diet may be also found. However, if our diet is healthy, we do not need to use them. Furthermore, they are only applied in certain situations with an example being immunodeficiency. In a group of persons who administered food supplements within the last year, more than a half of them used these products to complement everyday diet (54%) and strengthen immune system (52%) while for only 13% persons its intake was recommended by physician (13). Other information indicates that excessive vitamin consumption may affect the health and supplements for weight loss do not result in the reduction of adipose tissue (16). Advertisements available on the Internet, however, do not suggest that supplements should be purchased from credible sources. It also applies to the products bought via Internet. In this respect, a possibility of control is rather limited. Thus, the products offered on the Internet may be falsified or contain substances which are not listed in their composition. They may also be composed of active substances or their analogues which are used in medicinal product manufacturing or even substances whose usage is forbidden by law provisions. Consequently, it may lead to health-and life-threatening conditions. Out of 8 terms, Google suggested 5 terms concerning the content of this article, i.e. diet, weight loss or supplements for joints. Having analyzed the search results for food supplements, Internet user may encounter a broad scope of information, ranging from legal regulations (6), online shopping, manufacturer s websites to the portals with articles warning against the risk of unreasonable use of supplements or hazardous substances identified in some weight loss products (17, 18). A list of search results for supplement for weight loss includes mainly shops, forums/online social networking services, where the information on products available on the market can be exchanged. Exclusively

13 No 4 Food supplement related risks in the light of Internet 617 two search results referred to opinions based on scientific evidence, i.e. what are supplements for weight loss and what is their mechanism of action. In case of supplement for joints, similar situation was observed (Fig.2). Fig.4 Google.pl suggestions for supplements - percentages. Fig.2 Google.pl suggestions for supplement. Having modified the search term by supplements (singular replaced by plural form), 100% of results referred to food supplements. Additionally, one search result concerned the definition while the remaining ones were with regard to shops. The latter concentrated on the sale of supplements for sportsmen and gym s clients. These products are also referred to as sport nutrients (Fig.3). Fig.3 Percentage of links referring to food supplements (search term - supplements ). Suggestions for supplements were mainly portals with information for persons interested in body composition, physical performance, muscle building or weight loss. Search results included shops, forums and website of manufacturer of nutrients for sportsmen and persons attending gyms (Fig.4). Having entered the search term - supplements, the majority of results were with regard to diet. Most frequently, the searched supplements were designed for sportsmen (referred to as supplements for body composition, physical performance, muscle building). These websites, however, do not serve as the basis of information and education on food supplements. These are the websites concerning food supplement shops, then those presenting general information on such products and finally those regarding the products for weight loss. DISCUSSION Pursuant to the provisions of law, food supplements are a kind of foodstuffs. Therefore, they are subject to legal acts different from those applying for medicinal products. Such a fact may be used by unfair manufacturers. Furthermore, 50% of respondents wrongly claimed that the quality of food supplements is equally controlled as it is in the case of over-the-counter medicinal products (13). Consequently, it may lead to negative consequences for health. Due to the introduction of RASFF, aimed at protecting the consumers against hazardous products, the European Union allowed for the exchange of information on i.a. food supplements in the EU and EEA countries. In 2013, a total of 3,205 initial notifications were sent. For a group of the following products dietetic foods, food supplements, fortified foods, 160 events were notified, including 33, 19 and 55 alert, information and border rejection notifications, respectively while the remaining ones concerned information on follow-up activities. Having considered chemical contamination, a special attention should be paid to high concentrations of toxic metals (mercury - 9 notifications, lead - 9 notifications, arsenic - 4 notifications). It should be highlighted that several notifications concerned exceeding the maximum permissible concentrations for more than

14 618 Monika Wróbel-Harmas, Magdalena Krysińska, et al. No 4 one element. For one case, too high contamination with polycyclic aromatic hydrocarbons (PAH) was reported. Four notifications were with regard to poor microbiological quality of products. A specific reason, in fact limited to the use of food supplements, consists in using physiologically active, unauthorized substances to trigger metabolic or medicinal actions (about 60% of initial notifications). The most frequently listed chemical compounds are: DMMA (3,4-dimethoxy-N-methylamphetamine) - 7 notifications, phenolphthalein (7 notifications), sildenafil and its derivatives (13 notifications), synephrine (16 notifications), yohimbine (4 notifications), sibutramine (5 notifications) and other (10 notifications). Such substances were identified in herbal products or those containing plant extracts, frequently referred to as natural or traditional. They were not, however, declared on their label. Such substances were identified in products for weight loss (DMMA, phenolphthalein, synephrine, sibutramine) and erection (sildenafil and derivatives, yohimbine). Substances such as DMMA and other derivatives of amphetamine may trigger cardiac arrhythmia, which in extreme situations, may lead to circulatory failure and emaciation. Similarly, the analogues of ephedrine, e.g. synephrine may have such effects. Phenolphthalein is a compound of rapid laxative effect. Sildenafil use is contraindicated in persons diagnosed with ischaemic heart disease, hypertension, arrhythmia and with a history of recent myocardial infarction (19). Official Medicines Control Laboratory report, regarding the study of food supplements for weight loss, provided similar results concerning illegal and unauthorized active substances use (20). Supplements contain also materials which should be authorized as novel food. These are mainly products employed in the medicine of the Far East, which are not used as food in Europe. Scientific evidence, confirming the effect of these elements, is limited with an example being Corilus versicolor. Anti-cancer properties are attributed to this fungus, however, such action as well as its safety profile have not been scientifically confirmed. In case of food supplements, a problematic issue is the use of unauthorized active substances. Thus, it constitutes a challenge for the authorities liable for food control. There is a necessity of implementing a new range of tests, which so far have not been routinely associated with food safety. Such tests would allow for identification and quantitation of active substances as well as identification of unauthorized compounds. CONCLUSIONS 1. There is a necessity of systemic education of consumers on reasonable use of food supplements. 2. To obtain reliable information, confirming the composition and effect of food supplement, a potential consumer should first contact physician or dietician. Consumer may also search other sources for information with an example being health-related portals, where articles written by physicians or pharmacists are also accessible. 3. It is of importance to consider the initiation of alert system which would monitor adverse reactions resulting from the use of food supplements and novel food. 4. For official controls and food supplement monitoring, it is required to perform tests for identification and quantitation of active substances, identification of unauthorized compounds as well as drawing attention to a risk associated with microbiological and chemical contamination. REFERENCES 1. Frenkel M, Sierpina V. The use of Dietary Supplements in Oncology, Current Oncology report Dyrektywa 2002/46/WE Parlamentu Europejskiego i Rady z dnia 10 czerwca 2002 r. w sprawie zbliżenia ustawodawstw Państw Członkowskich odnoszących się do suplementów żywnościowych. 3. Rozporządzenie (WE) nr 178/2002 Parlamentu Europejskiego i Rady z dnia 28 stycznia 2002 r. ustanawiające ogólne zasady i wymagania prawa żywnościowego, powołujące Europejski Urząd ds. Bezpieczeństwa Żywności oraz ustanawiające procedury w zakresie bezpieczeństwa żywności. Dz.Urz. WE L 31, s Ustawa o bezpieczeństwie żywności i żywienia z dnia 25 sierpnia 2006r. (Dz.U. z 2010 r. Nr 136, poz. 914 z późn. zm.). 5. Rozporządzenie Ministra Zdrowia w sprawie składu oraz oznakowania suplementów diety z dnia 9 października 2007r. (Dz. U. z 2007 r. Nr 196, poz z późn. zm.) Rozporządzenie (WE) Nr 1924/2006 Parlamentu Europejskiego i Rady z dnia 20 grudnia 2006 r. w sprawie oświadczeń żywieniowych i zdrowotnych dotyczących żywności (Dz.U. L 404 z , str. 9). 8. Rynek produktów OTC w Polsce 2014, Prognozy rozwoju na lata , PMR, TNS OBOP Świadome samoleczenie w Polsce

15 No 4 Food supplement related risks in the light of Internet Fijałek Z., National Medicines Institute Poland, Official Medicines Control Laboratories. Received: Accepted for publication: Address for correspondence: Magdalena Krysińska National Institute of Public Health National Institute of Hygiene Department of Organization, Health Economics and Hospital Management Chocimska 24, Warsaw Tel , mkrysinska@pzh.gov.pl

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17 PRZEGL EPIDEMIOL 2014; 68: Problems of infections Joanna Ewa Drozd-Sokołowska 1, Grażyna Dulny 2, Anna Waszczuk-Gajda 1, Wiesław Wiktor-Jędrzejczak 1 AN ISOLATED OUTBREAK OF INFLUENZA A H1N1 IN A HAEMATOLOGICAL DEPARTMENT DURING POST-PANDEMIC PERIOD 1 Department of Haematology, Oncology and Internal Diseases, Medical University of Warsaw, Poland 2 Epidemiological Service, Central Clinical Hospital, Medical University of Warsaw, Poland ABSTRACT INTRODUCTION AND OBJECTIVE. Influenza A H1N1 virus strain was associated with the pandemic outbreak of febrile respiratory infections worldwide in 2009, however in August 2010, the WHO announced that the world had entered the postpandemic period. It offered specific recommendations for this period, including the identification of clusters of severe respiratory disorders and deaths. Here we report the fulminant course of influenza A H1N1 infection in the postpandemic period in a group of patients in a single hematology department. We make an attempt to identify potential risk factors and the mode of spreading, and to provide recommendations for best practice. MATERIAL AND METHODS. We conducted a retrospective analysis of a cluster of patients diagnosed with or suspected of influenza A H1N1 infection in the period from December 2010 to March RESULTS. Fourteen patients with hematological disorders unexpectedly developed acute respiratory failure ARDS (Acute Respiratory Distress Syndrome). Of them, nine tested positive for influenza A H1N1 in a screening test and eight in confirmatory polymerase chain reaction. The infection was fatal in nine patients, despite artificial ventilation in eight and oseltamivir administration in 11. Ten were in reverse isolation according to CDC. No similar cases occurred in the whole hospital concurrently, or in the hematology wards at any other time. CONCLUSIONS.The occurrence of A H1N1 epidemics in a hematological ward in the post-pandemic period highlights the importance of awareness of this complication, prompt testing and antiviral treatment. Furthermore, it confirms the importance of vaccinating patients and personnel against influenza as a prophylactic measure. Key words: influenza A H1N1, disease outbreak, complications INTRODUCTION In 2009, the influenza A H1N1 virus strain was associated with the outbreak of febrile respiratory infections worldwide, as declared by the World Health Organization (WHO). H1N1 infections were reported in more than 214 countries; there were more than 500,000 cases and 18,849 deaths (as of 1 August 2010) (1). In Poland, 400 laboratory-confirmed cases were reported from May 2009 to September 2010, resulting in 131 deaths (2). In August 2010, the WHO announced that the world had entered the postpandemic period and offered specific recommendations for action that should be taken during this period, including the identification of clusters of severe respiratory disorders and deaths (3). These recommendations were adopted in Poland. According to the data of the National Institute of Public Health, Warsaw, Poland, from the 6th of September 2010 to the 27th of March 2011, 226 A/H1(v) infections were confirmed in Poland. The data did not reveal either an increased frequency or severity of respiratory tract infections in the general population in this period (2). However, unexpectedly, from December 2010 to March 2011, a cluster of influenza A H1N1-positive cases occurred in a single hematology department. Herein, we describe and analyse this cluster. National Institute of Public Health National Institute of Hygiene

18 622 Joanna Ewa Drozd-Sokołowska, Grażyna Dulny, et al. No 4 MATERIALS AND METHODS The study was approved by Medical University of Warsaw Review Board. Patients. Influenza A H1N1 infection with a fulminant course was diagnosed or strongly suspected in 14 hematological patients in the Department of Hematology, Oncology and Internal Diseases, Medical University of Warsaw (Warsaw, Poland) between December 2010 and March During this period, 358 patients were hospitalised in our unit (190 female, 168 male; median age: 62 years, range: years). Concurrently, only four patients in all other hospital departments (992 beds, 12,748 hospitalisations) tested positive for H1N1 by polymerase chain reaction (PCR) and experienced only mild symptoms. There were no cases with a similar clinical course that were not tested for H1N1. Furthermore, there was no influenza A H1N1 epidemic in Warsaw or the rest of Poland at this time. The Division of Hematology. The Division of Hematology, in which the influenza outbreak occurred, comprises three wards adjacent to each other but with limited traffic between them. Ward A has 17 beds, Ward B 16 and Ward C 26. Each has separate nursing staff and two (Wards A and B) follow the procedures of reverse isolation. However, patients were admitted to these wards without quarantine providing they were asymptomatic for acute infections. In Ward C, there was open access for families and patients could walk freely outside the ward, including to the hospital cafeteria. Patient observation. Patients with symptoms that suggested a respiratory tract infection, including fever, dyspnoea, cough, and radiological signs suggesting interstitial pneumonia in high resolution computed tomography underwent a screening test for influenza A after the first patient tested positive for influenza A H1N1 (the second patient in the described cohort). Confirmatory PCR for influenza A H1N1 was performed in all patients who tested positive in the screening test. PCR was also performed for some patients whose screening test was negative but whose symptoms strongly suggested influenza infection. Other necessary blood tests and scans were performed, depending on particular circumstances and indications. PCR testing for the clearance of viruses from respiratory secretions after the symptoms of infection had been eliminated was not performed routinely. Tests used for laboratory diagnosis of influenza A H1N1 virus infection Influenza screening test. The Influenza A/B 2 Panel Test 4A470 by Gecko Pharma Vertrieb GmbH (Ahrensburg, Germany) was used for the initial diagnosis of influenza. The sensitivity of the test is 76.3%, while the specificity 92% according to the manufacturer. Polymerase chain reaction test. Mucosal smears from nose and throat were the source of viral genetic material. Nucleic acids were extracted from the samples using a High Pure Viral Nucleic Acid Kit (Roche Applied Science, Penzburg, Upper Bavaria, Germany) according to the manufacturer s instructions. Real-time reverse transcription (RT)-PCR was performed using a Quantification of Swine H1N1 Influenza Human Pandemic Strain Advanced Kit and Precision OneStep TM qrt- PCR MasterMix (PrimerDesign Ltd., Southampton UK). The reaction mix was prepared according to the manufacturer s instructions with minor modifications. A β-actin gene fragment was amplified for each sample to confirm the extraction of a valid biological template and to exclude PCR inhibition. One-step real-time RT PCR was performed in a Light Cycler 2.0 (Roche Applied Science). Reverse transcription (55 C, 10 minutes) and enzyme activation (95 C, 8 minutes) were followed by 50 cycles of denaturation at 95 C for 10 seconds and primer annealing and extension at 60 C for 1 minute; data was collected at the end of the final step. Method of retrospective analysis. The medical records of patients diagnosed with or suspected of having influenza A H1N1 were analysed to collect data on the type and status of underlying primary hematological disorder, complete blood count abnormalities, complications, effect of treatment on survival, and overall survival. In addition, the means of transmission was investigated. Statistical analysis. STATISTICA 9.0 software (Stat- Soft, Inc., Tulsa, OK, USA) was used for basic calculations. Continuous variables are expressed as the median and range. No statistical tests were performed, because of the small sample size. RESULTS Of the 14 patients analysed, eight tested positive for influenza A H1N1 by PCR and six either were not tested in the initial phase of the outbreak, or tested negative despite presenting symptoms that strongly suggested influenza. PCR-confirmed patients are described separately from other patients. None of the patients had been vaccinated against influenza in the preceding year. Of the hospital personnel, about half of the nurses and the majority of doctors were vaccinated, but unvaccinated personnel worked on every ward. The timing and mode of influenza A H1N1 transmission. Probably the first cases of influenza occurred throughout January and at the beginning of February Initially, two patients (one male, one female) with no formal confirmation of influenza developed respiratory insufficiency. In one, no diagnostic tests were performed; in the other, negative screening results were obtained and PCR testing was not performed. They were hospitalised in the reverse isolation ward (A) in our division, as described in the Patients and Methods.

19 No 4 An isolated outbreak of influenza AH1N1 623 Both patients required mechanical ventilation for respiratory failure. The clinical course in the male patient (with negative screening results) was complicated by intracranial hemorrhage and multiorgan failure with disseminated intravascular coagulation in the early post transplantation period. In the female patient, respiratory insufficiency remained the primary problem. At the end of January, two new cases occurred in the second (B) reverse isolation ward (one confirmed, one highly suggestive; both negative on screening tests; both with severe respiratory insufficiency that required mechanical ventilation following clinically overt extensive bleeding in the respiratory tract. Approximately 1 week later, a new case was diagnosed in the free-access ward (C). Notably, at the same time, another patient visited an outpatient unit located on the same floor and died shortly afterwards from respiratory failure, in a regional hospital. The two patients in whom influenza was suspected had been hospitalised in a reverse isolation unit for a long time, so it is unlikely that they were infected by other patients. There were following possibilities of occurrence of such infections, either (i) patients were infected by asymptomatic staff, or (ii) they had latent infections and the pathogens were activated as a result of decreased immunity, or (iii) they were infected in the out-hospital environment and admitted to the hospital before development of symptoms, which could be the case of a female patient. It is worth mentioning, that during that period there was no increase in influenza incidence in the general population. The second outbreak of influenza occurred in early March 2011, with the majority of cases being diagnosed in Ward B (four PCR-confirmed cases in two adjacent rooms), one in reverse isolation Ward A and two (positive screening, negative PCR) in free-access Ward C. Representative case. A 48-year-old woman was admitted to our department in December 2010 with relapsed acute myeloid leukaemia (AML) following allogeneic hematopoietic stem cell transplantation (SCT). Flow cytometry of the cerebrospinal fluid revealed the presence of blasts, which indicated treatment with highdose cytosine arabinoside. During the pancytopaenia period following treatment, the patient experienced fever but there was no obvious local infection. She received broad-spectrum antibiotics and was tested for influenza, with a negative result. High-resolution computed tomography was performed to locate the cause of fever; this revealed ground-glass opacities, which suggested alveolar hemorrhage. Initially, the patient did not complain of dyspnoea, but her condition deteriorated within hours and blood gas analysis revealed respiratory failure, with an arterial oxygen partial pressure of 36.5 mm Hg. Oxygen therapy and glucocorticosteroids were initiated. Mechanical ventilation was implemented 4 days later for respiratory arrest. Despite intensive antibiotic and symptomatic treatment, the patient s condition did not improve: she bled actively from the respiratory tract and blood gas analysis showed increasing CO 2 retention, with continuously low O 2 pressure. Diagnostic tests for influenza were repeated and both screening and confirmatory PCR tests were positive. The patient received oseltamivir at a standard dose administered through nasogastric feeding tube from the day of positive screening results, which was 7 days after initiation of mechanical ventilation. However, her status deteriorated and she died on the next day, with signs of bleeding in the respiratory tract. It is worth mentioning that the patient was the first in the analyzed cohort with confirmed A H1N1 infection. Patients with confirmed influenza A H1N1 infection. Influenza A H1N1 infection was confirmed in two males and six females (median age: 57.5 years). Four patients had AML (one in first complete remission during consolidation chemotherapy, two during induction chemotherapy and one in relapse after allogeneic SCT); two had acute lymphoblastic leukaemia (ALL; 77 and 155 days, respectively, after allogeneic SCT); one had myelodysplastic syndrome with accompanying tuberculosis; and one had light chain amyloidosis with heart involvement, treated by autologous peripheral blood SCT. The median time from the first onset of symptoms to the diagnosis of influenza was 3 days (range: 0 11 days). One patient was asymptomatic. The time from the onset of symptoms to the start of treatment with oseltamivir ranged from 0 to 11 days (median: 2 days). At diagnosis, three patients had neutropaenia <0.5 G/l, three had a neutrophil count from G/l and two had a normal neutrophil count. Five patients had lymphopaenia <0.8 G/l (Grade 2 based on the Common Terminology Criteria for Aderse Events version 3.0 (4) prior to the onset of influenza, while only three had lymphopaenia below 0.3 G/l (as defined in the work of Ljungman (5)). The median duration of lymphopaenia <0.8 G/l was 10 days (range: 3 25 days) and 0 days (range: 0-25 days) for lymphopaenia <0.3 G/l. Seven patients were thrombocytopaenic (median: 27 G/l; range: 2 68 G/l) and seven were anaemic (median: 9.7 g/dl; range: g/dl). All patients except one had elevated acute-phase proteins (C-reactive protein). Four patients had concomitant respiratory disease (pneumonia of different aetiology). High-resolution computed tomography revealed ground-glass opacities, alveolar opacities, thickening of the septa and possible alveolar hemorrhage. Six patients developed respiratory insufficiency; four of these required mechanical ventilation. The major problem in these patients was CO 2 retention. In addition, three patients experienced renal failure (one requiring hemodialysis) and four experienced hypotension and septic shock.

20 624 Joanna Ewa Drozd-Sokołowska, Grażyna Dulny, et al. No 4 Five patients died as a result of complications to their underlying hematological disease that were due to influenza. The cause of death was multiorgan failure in two patients, septic shock caused by Enterococcus species in one, respiratory system hemorrhage in one and sudden cardiac death in one patient who was suffering from amyloidosis with heart involvement. Three patients who survived received oseltamivir for days (median: 11 days). A clearance PCR test was performed in only one patient and was negative after treatment was stopped. Notably, four nonhematological patients who were confirmed by PCR to have influenza A H1N1, treated outside our division in the same hospital at approximately the same time, and treated in internal medicine departments rather than in intensive care units recovered quickly. All of these were discharged after 5 14 days of hospitalisation. Patients with symptoms that suggested influenza infection, i.e. unexplained fever, dyspnoea, cough, bleeding in the respiratory tract and respiratory insufficiency. Four male and two female patients had such symptoms. Their median age was 49 years (range: 41 69) and were suffering from the following diseases: AML, ALL, multiple myeloma, chronic myelomonocytic leukaemia, T-cell prolymphocytic leukaemia and diffuse large B-cell lymphoma. Two patients showed symptoms that suggested influenza after allogeneic SCT (during the procedure and 1 year thereafter) and one following autologous peripheral blood SCT (+14 days). Two patients had a positive screening test but negative confirmatory PCR; one had a negative screening test with no PCR; one did not have any tests performed for technical reasons; and one died of fulminant respiratory failure shortly after visiting an outpatient unit in a regional hospital. Before the onset of symptoms that suggested influenza, five patients experienced lymphopaenia <0.8 G/l and two <0.3 G/l. The median duration of lymphopaenia <0.8 G/l was 3 days (range: 2 19 days), while for <0.3 G/l it was 0 days (range: 0-12 days). At the onset of infection, two patients were severely neutropaenic (0 G/l), one had a neutrophil count of 0.7 G/l and two had a normal neutrophil count. Five patients were thrombocytopaenic (median: 34 G/l; range: 4 53 G/l) and five were anaemic (median hemoglobin concentration: 8.7 g/dl; range: g/dl). Five patients required oxygen therapy for respiratory insufficiency; four of these required mechanical ventilation. Similarly to the confirmed group, one patient developed renal failure and one patient bled from the respiratory system. Four patients died in the course of suspected influenza: three from respiratory failure and one from multiorgan failure. Both surviving patients had a positive screening test (one was lost to follow-up after several months). DISCUSSION We have described the dramatic course of influenza A H1N1 infection in the postpandemic period in a group of patients in a single hematology department. It is important to stress that, at the time, there was no outbreak of influenza in the general population. Furthermore, when there was an outbreak of influenza A H1N1 in the season in the general population, we experienced only a few cases with a benign course and a similar situation did not occur during the subsequent 18 months. It is not possible to establish the origin of infection in particular patients, but three mutually compatible possibilities must be considered. Firstly, patients could have been infected asymptomatically prior to admission and have developed full-blown disease after chemotherapy or as the result of immunodeficiency in the course of their underlying blood disorder. Secondly, they could have been infected by infected personnel who were asymptomatic, particularly those who violated isolation procedures. Thirdly, patients could have been infected by each other, especially as there was no contact isolation. None of these possibilities can be excluded and more than one may well have been operative. It is highly unlikely that there was a single point of origin for the outbreak, for example, a single infected patient or member of staff who was case zero, because patients and personnel in different wards do not have contact with each other. Only during the second outbreak of influenza the majority of affected were patients hospitalised in the reverse isolation unit (B); patients were housed in adjacent rooms and allowed to leave them, which rendered it possible for them to infect each other. That patients infected one another is very likely in this situation. Although the virus usually causes acute infection and does not persist in infected individuals (6), the activation of latent infection cannot be excluded in at least some immunocompromised patients. There is little published data on A H1N1 virus biology in severely immunocompromised patients, e.g. after hematopoietic stem cell transplantation, but on the basis of such data as there is, some authors suggest prolonged viral shedding (7,8). Souza et al. (9) showed that the median duration of viral shedding in a population of influenza A H1N1-infected cancer patients receiving immunosuppression was 23 days, with the full range being from 11 to as many as 63 days. Therefore, in our opinion, it is possible that some patients acted as reservoirs for the virus. There is no way of determining the relative likelihood that the virus was spread by asymptomatic patients or personnel, or by patients who were already showing symptoms (the third possibility). However,