Bardzo tanie apteki z dostawą w całej Polsce kupic viagra i ogromny wybór pigułek.


Listeriosis: a resurgent foodborne infection 1) Austrian Agency for Health and Food Safety (AGES), Binational Austrian–German Listeria Reference Centre, Vienna and 2) Institute for Milk Hygiene, Milk Technology and Food Science, Department for Farm Animals and Public Veterinary Health, Vienna, Austria Listeria monocytogenes is the causative agent of human listeriosis, a potentially fatal foodborne infection. Clinical manifestations range from febrile gastroenteritis to more severe invasive forms, including sepsis, meningitis, rhombencephalitis, perinatal infections, and abor- tions. In recent years, an increasing rate of listeriosis has been reported in several European countries. These increases primarily reflect a higher rate of bacteraemic listeriosis in those ‡65 years of age, and are not otherwise correlated with geography, gender, ethnicity, socioeconomic factors or infectious serotypes. In the late 1980s, an upsurge in listeriosis rates was due to the contamination of a small number of food products. However, a restricted range of strains was responsible for most of the additional cases at that time, and no evidence exists for such a pattern since 2001. From a clinical perspective, the importance of isolating the pathogen as a prerequisite for an accurate epidemiological investigation and ultimately stopping transmission cannot be overemphasized.
Keywords: Foodborne, incidence, lethality, Listeria monocytogenes, listeriosis, review Corresponding authors and reprint requests: F. Allerberger,Austrian Agency for Health and Food Safety (AGES), BinationalAustrian–German Listeria Reference Centre Spargelfeldstraße 191,1220 Vienna, AustriaE-mail: franz.allerberger@ages.atandM. Wagner, Institute for Milk Hygiene, Milk Technology and FoodScience, Department for Farm Animals and Public Veterinary Health,Veterinaerplatz 1, 1210 Vienna, AustriaE-mail: temperatures, allowing for growth even in properly refriger- In recent years, an increasing rate of listeriosis has been Listeriosis is a rare but potentially serious infection caused reported in several European countries [3–10]. These by Listeria monocytogenes. This organism can be found increases primarily reflect a higher rate of bacteraemic liste- throughout the environment in soil, vegetation and animals.
riosis in those ‡65 years of age, and are not otherwise The main route of transmission is believed to be through correlated with geography, gender, ethnicity, socioeconomic consumption of contaminated food. However, infection can factors or infectious serotypes [6,7]. The Annual Epidemiolog- also be transmitted, albeit very rarely, directly ical Report on Communicable Diseases in Europe 2008 states: infected animals to humans, as well as between humans [1].
‘‘There appears to have been a significant increasing trend in In neonatal infections, L. monocytogenes can be transmitted the listeriosis notification rate in the EU from 2003 to 2006’’ from mother to child in utero or during passage through [11]. Half (53.8%) of the EU member states with confirmed the infected birth canal. There are also rare reports of nos- cases also reported an increasing trend during the 2-year per- ocomial transmission attributed to contaminated material or iod 2006–2007 [12]. The cause of this increasing incidence, patient-to-patient transmission via healthcare workers [1].
which, as shown in Fig. 1, was still ongoing in 2008, in Austria The bacterium is particularly successful in causing food- at least, is unknown. A total of 1554 confirmed cases of liste- borne disease, because it survives food-processing technolo- riosis were reported from 26 EU member states in 2007. The gies that rely on acidic or salty conditions [2], and, unlike EU notification rate was 0.3 per 100 000 population [12].
many pathogens, can continue to multiply slowly at low Incidences for six EU countries are given in Fig. 2 [13].
ª2009 The AuthorsJournal Compilation ª2009 European Society of Clinical Microbiology and Infectious Diseases Listeriosis: a resurgent foodborne infection Number of cases
1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 FIG. 1. Absolute number of cases of invasive listeriosis, Austria 1997–2008 (n = 181).
Listeriosis during pregnancy is a serious threat to the unborn child. One-third of culture-confirmed cases of mater- nal–fetal infections result in abortion or stillbirth. However, L. monocytogenes causes two forms of listeriosis: non-invasive the prognosis for live-born babies is good, even in those gastrointestinal listeriosis and invasive listeriosis. In immuno- severely ill [10]. Pregnancy-associated cases refer to listerio- competent individuals, non-invasive listeriosis develops as a sis in pregnant women or in the neonates (up to 28 days of typical febrile gastroenteritis. In immunocompromised adults, life), and the non-pregnancy-associated cases to older babies such as the elderly and patients receiving immunosuppressive (>28 days) [1]. Most maternal infections occur during the agents, listeriosis can manifest as septicaemia or meningoen- third trimester of pregnancy, when T-cell immunity is most cephalitis. Invasive listeriosis can also be acquired by the impaired. Infected women typically develop non-specific flu- fetus from its infected mother via the placenta [13]. Perinatal like symptoms but may remain asymptomatic. Listeriosis has listeriosis can lead to abortion, birth of a stillborn fetus or a rarely been observed during the first trimester [14].
baby with generalized infection (granulomatosis infantiseptica), In non-pregnancy-associated cases, listeriosis mainly mani- and sepsis or meningitis in the neonate. Neonatal listeriosis fests as meningoencephalitis or septicaemia. The median is subdivided into two clinical forms: early-onset (usually incubation period is estimated to be 3 weeks. Outbreak defined as occurring within the first week of life) and late- cases have occurred 3–70 days following a single exposure onset. The late-onset type may occur from one to several to an implicated product. The onset of meningoencephalitis, which is rare in pregnant women, can be sudden, with fever, intense headache, nausea, vomiting and signs of meningeal irritation, or may be subacute, particularly in an immunocom- promised or elderly host. Rhombencephalitis involving the brainstem is an unusual form of listeriosis. L. monocytogenes can also produce a wide variety of focal infections; cases of conjunctivitis, skin infection, lymphadenitis, hepatic abscess, pleuropulmonary infection, joint infection, osteomyelitis, pericarditis, myocarditis, arteritis, necrotizing fasciitis and endophthalmitis have been described [1,15–18]. In Europe, approximately 10–20% of clinical cases are pregnancy-associ- Cases/100 000
ated (including neonates within the first 4 weeks of birth), but the majority of cases occur in non-pregnant immuno- compromised individuals, especially the elderly. Approxi- mately 10% of patients have no known risk factor or underlying disease predisposing them to infection with Listeria [6]. In Austria in 1997–2007, patients without known risk FIG. 2. Listeriosis incidence in six EU countries, 1999–2007 (modi- fied from Eurosurveillance, with permission).
45.2 years; median, 46.6 years). The overall mean age of the Journal Compilation ª2009 European Society of Clinical Microbiology and Infectious Diseases, CMI, 16, 16–23 Clinical Microbiology and Infection, Volume 16 Number 1, January 2010 Austrian non-pregnancy-associated listeriosis patient in that 181 cases of invasive listeriosis documented in Austria from period was 64.3 years (median, 66.2 years; range, 0.8– 1997 until 2008, only one patient was human immunodefi- 93.5 years), i.e. significantly greater than the age of patients ciency virus-positive [6] (unpublished data, F.A.). A partial explanation may lie in the experimental observation that resistance to listeriosis appears to be mediated by lym- phocytes that do not carry CD4 or CD8 markers [24].
In addition, it is likely that many cases are prevented by routine Pneumocystis jirovecii prophylaxis with trimethoprim– Clusters, suspected or confirmed to represent community outbreaks, have contributed to the recent increased inci- dence in some countries. In 2005, ten cases of listeriosis in a small area of Switzerland were due to locally made and dis- tributed soft cheese [19]. In 2006, the Czech Republic expe- Listeriosis is diagnosed by a positive culture from a normally rienced one large outbreak, involving 78 patients, of whom sterile site. L. monocytogenes can be readily cultured from 13 died; here also, soft cheese was identified as the source clinical specimens such as blood, cerebrospinal fluid (CSF), [3]. During the period 2006–2007, Germany recorded an amniotic fluid, placenta, meconium, lochia, gastric washings outbreak of 16 cases caused by presliced ready-to-eat (RTE) or ear swabs from newborns, by directly plating the material delicatessen meat (sausage salad) (International Meeting on onto blood agar plates and incubating overnight at 35°C in Emerging Diseases and Surveillance, 2009, Abstract 10.098).
an ambient atmosphere. Stool specimens (other than meco- In 2008, Austria experienced an outbreak of febrile gastro- nium) should be selectively enriched for Listeria before being enteritis, including three cases of invasive listeriosis associ- plated on selective agar media. Classic cold enrichment over ated with jellied pork contaminated with L. monocytogenes months is no longer necessary. PCR is the only test utilized [20]. However, the overall proportion of cases related to for rapid detection of L. monocytogenes in clinical specimens.
clusters remained stable and low; therefore, these clusters The PCR assay is particularly useful when prior administra- did not account for the increased incidence in Austria.
tion of antimicrobial agents is likely to compromise culture.
Various test protocols were evaluated for CSF samples and tissue samples (fresh or in paraffin blocks). Gram staining Whereas much has now been learned about epidemic listeri- and microscopic examination of CSF or meconium permit osis, little is known about sporadic listeriosis, which, in fact, only a presumptive diagnosis. For clinical specimens, the represents the majority of cases [5]. Dietary risk factors for importance of isolating the pathogen as a prerequisite for sporadic listeriosis have been assessed through case–control an epidemiological investigation and appropriate infection studies. In a study conducted during the period 1986–1987 control cannot be overstressed [25].
in the USA, case patients were significantly more likely than Because listeriosis during pregnancy is serious and difficult controls to have eaten uncooked or non-reheated hot dogs to diagnose, blood cultures should be considered for any (frankfurters) or undercooked chicken. An estimated 20% of pregnant woman presenting with fever, especially if accompa- the overall risk of listeriosis was thought to be attributable to nied by flu-like or gastrointestinal symptoms [26]. Vaginal or consumption of these foods [21]. Another study performed stool cultures are not helpful in diagnosis, because some in the USA from 1988 to 1990 found that case patients were women are asymptomatic carriers [26]. Indeed, faecal car- significantly more likely than controls to have eaten soft riage of L. monocytogenes occurs in 1–15% of the population cheeses or delicatessen foods [22]. Other exposures associ- [27]; the incidence of women carrying L. monocytgenes in the ated with an increased risk of sporadic disease included recent use of antacids, laxatives or H2-receptor antagonists Listerial rhombencephalitis is a rare manifestation of liste- [22]. Dietary risk factors for sporadic listeriosis were also riosis. In contrast to other listerial infections of the central examined in a study in Denmark; drinking unpasteurized milk nervous system (CNS), the majority of listerial rhomben- or eating pate´ were the only risk factors identified [23].
cephalitis cases occur in previously healthy adults; no cases Although listeriosis is said to be 100–1000 times more have been reported in infants [28]. Blood cultures may or common in patients with AIDS than in the age-matched gen- may not reveal growth of the organism in these cases.
eral population, it is somewhat surprising that it is not seen Serological responses to commercially available whole cell more commonly, given the ubiquity of the organism. Among ª2009 The AuthorsJournal Compilation ª2009 European Society of Clinical Microbiology and Infectious Diseases, CMI, 16, 16–23 Listeriosis: a resurgent foodborne infection suspensions O and H) are not diagnostic, because of anti- should be taken to establish and document true penicillin genic cross-reactivity between L. monocytogenes and other allergy prior to starting treatment with these second-line Gram-positive bacteria such as staphylococci, enterococci agents. Transplacental passage of erythromycin has been and Bacillus species [29]. Furthermore, patients with culture- shown to provide subtherapeutic concentrations in both the confirmed listeriosis have been known to have undetectable amniotic fluid and fetal serum [36]. Therefore, many experts antibody levels. Positive serological findings must be treated recommend using an alternative. Vancomycin has also been with caution and, in cases other than rhombencephalitis, used in cases of bacteraemic listerial infection [37]. However, exact diagnosis should be based on detection of the patho- the results obtained from a model of rhombencephalitis in gen. Serological responses to listeriolysin O (LLO) are sup- gerbils strongly suggest that intravenous vancomycin is unli- posed to be more reliable [30]. An ELISA for the detection kely to be effective in patients with CNS infection [35]. Lin- of anti-LLO IgG in human serum and plasma is commercially ezolid is another agent that has been used successfully to available (DIATHEVA, Fano, Italy). LLO, a polypeptide pro- treat listerial infections [38]. Other antibiotics used in cases tein secreted by L. monocytogenes, is a major virulence factor of listeriosis include meropenem and rifampicin [39]. It has produced by all pathogenic L. monocytogenes strains but been speculated that, at least in the immunocompromised released in the culture medium only at low levels. For this host, the addition of rifampicin, which is effective against reason, the LLO protein, used in the DIATHEVA assay as intracellular L. monocytogenes and will penetrate the CSF, test antigen, is expressed in Escherichia coli.
could help to eradicate residual bacteria [32]. Resistance has been reported with rifampicin monotherapy [33]. Kayser et al. [40] reported, as early as 1989, good in vitro activity of meropenem. Another study with this antibiotic showed good activity in experimental meningitis in guinea pigs [41].
In vitro, L. monocytogenes is susceptible to a wide range of L. monocytogenes reproduces in the reticuloendothelial sys- antibiotics, with the exception of fosfomycin, first-generation tem and survives intracellularly after uptake by macrophages quinolones and third-generation cephalosporins, although a [33]. The bone marrow might be a unique niche for L. mono- few exceptional strains exist. Susceptibility testing is usually cytogenes [42]. This means that the organism cannot be performed using Mueller–Hinton agar, with or without blood reached by certain antibiotics; this might contribute to the (5% horse blood or 5% sheep blood) [31]. For trimetho- differences between in vitro and in vivo results. Macrolides prim–sulphamethoxazole, the blood is lysed. Antimicrobial and quinolones accumulate within host cells and may attack in vitro susceptibilities of Listeria have not changed markedly the intracellular Listeria organisms. Moxifloxacin may be a over the past 35 years [31,32]. Although optimal therapy has promising candidate; however, no clinical trials have provided not been verified by randomized clinical studies, penicillin firm evidence [43]. L. monocytogenes is intrinsically resistant or ampicillin alone, or in combination with gentamicin, are to nalidixic acid (MIC >128 mg/L) and shows decreased sus- considered to be the drugs of choice. The clinically effective ceptibility to therapeutically important fluoroquinolones, such antibiotics penicillin and ampicillin are only bacteriostatically as ciprofloxacin (MIC 0.5 – 2 mg/L) [44]. In an animal model, effective against L. monocytogenes, thus emphasizing the impor- ciprofloxacin was only weakly active in the spleen, liver and tance of the body’s own cellular defence mechanisms [33].
CNS [35]. However, the newer derivatives of the quinolones Addition of gentamicin has not been proven to be clini- (e.g. levofloxacin and moxifloxacin) exhibit strong bacterici- cally advantageous, as synergy has only been demonstrated dal activity against L. monocytogenes [45,46].
in vitro [34]. Moreover, in animal models, gentamicin does Antimicrobial drugs that are of questionable value in ani- not reliably show a synergistic effect [35]. A gentamicin- mal experiments or for the treatment of human listeriosis supplemented protocol should not be prescribed for preg- include clindamycin and aminoglycosides when administered nant women, because of possible teratogenic effects [2,33].
individually [33]. Cephalosporins have hardly any in vitro As Listeria does not produce b-lactamase, the addition of effect against L. monocytogenes. The reason is the minimal or b-lactamase inhibitors in the treatment of listeriosis is non-existent affinity of listerial penicillin-binding proteins 3 ineffective. There is no relevant difference between the MIC and 5 for cephalosporins [47]. Despite good in vitro activity, values of ampicillin alone and ampicillin combined with even cephalothin had no effect on experimental listeriosis in sulbactam for the treatment of infection due to L. monocyto- mice [33]. In addition, cephalothin lacks satisfactory CSF pen- etration. Reports of therapeutic failures prove that cephalo- For patients with b-lactam allergy, trimethoprim–sulpha- sporins are not indicated for the treatment of listeriosis methoxazole or erythromycin may be considered. Steps Journal Compilation ª2009 European Society of Clinical Microbiology and Infectious Diseases, CMI, 16, 16–23 Clinical Microbiology and Infection, Volume 16 Number 1, January 2010 Fosfomycin was previously considered to be ineffective in ampicillin and trimethoprim–sulphamethoxazole, for which treating listeriosis, as revealed by in vitro laboratory data clinical CLSI breakpoints for Listeria susceptibility testing are [33]. Therefore, despite achieving theoretically excellent con- defined, the usual CLSI criteria for staphylococci are applied centrations in brain and other tissues, fosfomycin has not been used in the management of listeriosis. However, in 1979, a report demonstrated that fosfomycin might have a positive effect on L. monocytogenes infections in mice [49].
Recent research has demonstrated that the effect of fosfo- mycin on L. monocytogenes is dependent on the expression of At present, there is no immunization available for listeriosis.
the Hpt protein encoded by the hpt gene, which is under the Engineered live-attenuated L. monocytogenes, which elicits control of the central virulence regulator protein PrfA. Hpt, strong cellular immune responses, is currently being evalu- ated in clinical trials as an anticancer vaccine [55]. The utility, enables L. monocytogenes to use hexose phosphates from the or even the feasibility, of eradicating gastrointestinal coloniza- host cell cytosol as an energy source, enabling intracellular tion to prevent invasive listeriosis is unexplored. However, movement. As the virulence regulator gene prfA is switched asymptomatic individuals at high-risk of listeriosis, who are off extracellularly, Hpt becomes downregulated and L. mono- known to have ingested a food implicated in an outbreak, cytogenes is resistent to fosfomycin in in vitro suceptibility could reasonably be given 7 days of oral ampicillin or tests. However, upon upregulation of the virulence regulon trimethoprim–sulphamethoxazole treatment [20,56].
during infection, L. monocytogenes becomes susceptible to fosfomycin. BALB/C mice, as used in in vivo tests, survived a challenge of 108 CFUs per mouse, whereas the LD50 in con-trols was 1.77 · 104 CFUs of L. monocytogenes [50].
It is generally recommended that patients should be trea- Listeriosis is essentially a foodborne disease, and this is no ted for at least 14 days [33]. Even if a host appears to be longer questioned. The upsurge in listeriosis rates in the late clinically improved, the intracellular concentration resulting 1980s was due to contamination of a variety of food prod- from short-course antibiotic treatment may not be sufficient ucts, including coleslaw, unpasteurized milk and Mexican-style for complete sterilization. Indeed, in immunosuppressed soft cheese [1]. A restricted range of strains was responsible patients, relapses have been reported after 2 weeks of peni- for most of the additional cases at that time, and most cillin therapy [51]. In pregnancy, there are additional consid- human cases are still associated with L. monocytogenes sero- erations, such as adequate treatment of the placenta, and vars 1/2a, 1/2b and 4b. Whereas the number of reported potential ongoing infection of the fetus or placenta. There cases was quite stable during the period 1996–2002, an has been concern that placental infection may not be clini- increase was observed again during the period 2003–2007.
cally apparent, but could progress once antibiotic therapy Currently, it appears that the numbers of cases of listeriosis has been withdrawn. For this reason, some experts have sug- are stable in some countries, or, as in Germany, have gested at least 3–4 weeks of treatment during pregnancy returned to those recorded previously.
[37]. Patients with rhombencephalitis should be treated with The reasons for the changing incidence of listeriosis antibiotics for at least 6 weeks [28].
remain unclear. No evidence exists for a causative role of Although there are no data concerning the efficacy of anti- gradual demographic or behavioural changes. Cairns and microbials in listerial gastroenteritis, it could be argued that, Payne [7] postulated that this phenomenon might be a in both symptomatic and asymptomatic persons known to consequence of changes in government policy regarding busi- have ingested a food implicated in an outbreak, and who ness practices that have had widespread effects on food pro- have a high risk of invasive disease because of underlying cessing, distribution and preparation. Goulet et al. [5] illness, pregnancy or age (elderly), it might be prudent to hypothesized that the recently reduced salt content in RTE administer oral amoxycillin or trimethoprim–sulphamethox- products may contribute to the growth of the organism, if azole for 7 days [20]. Recently developed protocols employ- present as a contaminant, and increase the likelihood of ing gerbils and genetically engineered mice now allow the infection when these products are consumed by susceptible effect of antibotics to be studied in animal models relevant individuals. The food industry reduced the salt content of selected products, such as RTE meat products, in response The CLSI has not yet provided specific guidelines for in vitro to recommendations in 2002 from food safety agencies, ask- ing for a 20% reduction in average salt intake, spread over ª2009 The AuthorsJournal Compilation ª2009 European Society of Clinical Microbiology and Infectious Diseases, CMI, 16, 16–23 Listeriosis: a resurgent foodborne infection 5 years, in order to prevent disease attributable to hyperten- Important control strategies from public health agencies sion-related conditions. Wagner et al. [57] studied samples include developing and maintaining timely and effective disease of RTE foodstuffs in Vienna, Austria. They found 4.8% of 946 surveillance programmes, as well as promptly investigating samples collected from 103 supermarkets to be positive for clusters of listeriosis cases. Routine characterization of L. monocytogenes, with five smoked fish samples exceeding human, food and environmental isolates, and utilization of the tolerated limit of 100 CFUs per gram of food. Products large-scale subtype databases, will hopefully facilitate Europe- showing the highest contamination rate were fish and sea- wide outbreak detection and control in the near future [60].
food (19.4%), followed by raw meat sausages (6.3%), soft cheese (5.5%) and cooked meat products/pate´s (4.5%). The overall contamination rate of 640 RTE foodstuffs collected at the household level was 1.7%. Importantly, most high-risk foods were collected from households of elderly individuals.
L. monocytogenes has been recognized as a human pathogen Pulsed-field gel electrophoresis typing of the collected for more than 80 years. The demographic shift and the wide- L. monocytogenes isolates revealed a high degree of diversity spread use of immunosuppressive medications, to treat among the isolates collected at the household level. More- malignancy and manage organ transplantation, have increased over, evidence from EU-wide routine food safety investiga- the immunocompromised population at increased risk of lis- tions indicates that a substantial proportion of RTE products teriosis. Moreover, consumer lifestyles have changed, such may be contaminated by L. monocytogenes [12]. L. monocytoge- that less time is available for food preparation and more RTE nes was detected in 1.8% of RTE meat products and meat and takeaway foods are consumed. Changes in food produc- tion and technology have led to the production of foods with >100 CFUs/g), in 2.5% of RTE products and meat prepara- longer shelf-lives that are typical ‘Listeria-risk foods’, because tions of pork (in 0.6% with >100 CFUs/g), in 2.6% of RTE the bacteria have time to multiply, and the food does not products and meat preparations of poultry (in 0.7% with undergo a listericidal process, such as cooking, before con- >100 CFUs/g), in 1% of soft and semi-soft cheeses made sumption. Unlike infection with other common foodborne pathogens, listeriosis is associated with a high case-fatality >100 CFUs/g), and in 18.3% of RTE fish products (2.4% with rate of approximately 20–30% [61]. Epidemiological investiga- >100 CFUs/g) [12]. It is therefore essential to control foods tions during the past 30 years have shown that epidemic lis- that permit L. monocytogenes to grow to numbers exceeding teriosis and sporadic listeriosis are mainly caused by the arbitrarily defined minimal infectious dose of 105 CFUs consumption of contaminated food. Nevertheless, despite per gram or millilitre of foodstuff. However, the dose– the high rates of contamination of certain foods with L. mon- response relationship remains unclear [58]. Strain-specific dif- ocytogenes, listeriosis is a relatively rare disease as compared ferences in virulence seem to be of the utmost importance.
with other common foodborne illnesses, such as campylob- Newer risk assessment modelling suggests a 10)9 to 10)13 acteriosis or salmonellosis. However, because of its high probability of infection with a dose of 100 organisms, and a case-fatality rate, listeriosis is, after salmonellosis, the second 10)6 to 10)9 probability of infection at 1 000 000 organisms most frequent cause of foodborne infection-related deaths in Although exposure to L. monocytogenes cannot be avoided completely, proper food preparation and storage can decrease the risk. Pregnant women and immunocompro- mised individuals should be advised to avoid consumption of raw milk, unpasteurized soft cheeses, delicatessen meats, hot The authors declare that they have no conflict of interest.
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