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The epidemiology of human listeriosis
Microbes and Infection 9 (2007) 1236e1243 www.elsevier.com/locate/micinf
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The epidemiology of human listeriosis* Bala Swaminathan*, Peter Gerner-Smidt Foodborne and Diarrheal Diseases Branch, Division of Bacterial and Mycotic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road, MS C03, Atlanta, GA 30333, USA Available online 7 May 2007
Abstract Listeriosis is a serious invasive disease that primarily afflicts pregnant women, neonates and immunocompromised adults. The causative organism, Listeria monocytogenes, is primarily transmitted to humans through contaminated foods. Outbreaks of listeriosis have been reported in North America, Europe and Japan. Soft cheeses made from raw milk and ready-to-eat meats are high risk foods for susceptible individuals. Efforts by food processors and food regulatory agencies to aggressively control L. monocytogenes in the high risk foods have resulted in significant decreases in the incidence of sporadic listeriosis. Ó 2007 Published by Elsevier Masson SAS. Keywords: Listeriosis; Listeria monocytogenes; Epidemiology
1. Introduction Listeria monocytogenes is a Gram-positive bacterial species that occurs ubiquitously in nature. First described in 1926 as the cause of an epizootic outbreak in guinea pigs and rabbits [1], it was not until it caused a large outbreak of invasive disease with a high case-fatality rate in the maritime provinces in Canada [2] that it was recognized as a serious public health problem. This outbreak for the first time demonstrated L. monocytogenes as a foodborne pathogen and it is now believed that most cases of human listeriosis are foodborne. Since this outbreak there has been a tremendous interest in elucidating the epidemiology of this organism in order to protect the consumer against listeriosis in the most cost-effective manner. The bacterium possesses properties that favor it as a foodborne pathogen: at variance with most other pathogens it is relatively resistant to acid and high salt concentrations; it grows at low temperature, down to freezing point, which mean it may grow in refrigerated foods. Before the development of Listeria selective media, this property was used for selective
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Use of trade names is for identification only and does not imply endorsement by the Centers for Disease Control and Prevention or by the US Department of Health and Human Services. * Corresponding author. Tel.: þ1 404 639 3669; fax: þ1 404 639 3333. E-mail address: [email protected] (B. Swaminathan). 1286-4579/$ - see front matter Ó 2007 Published by Elsevier Masson SAS. doi:10.1016/j.micinf.2007.05.011
enrichment of the bacterium from complex matrices, with Listeria outnumbering the competing flora after incubation of the enrichment culture at refrigerator temperature for weeks or months. Additionally, L. monocytogenes readily produces biofilm that helps it to survive for prolonged periods in food production plants; an example of survival for more than 10 years in the same production environment has been described. Because of its ubiquitous nature, L. monocytogenes commonly contaminates raw produce and, through cross-contamination, other food items. Thus, all human beings are routinely exposed to L. monocyotgenes. Despite this, listeriosis is a relatively rare disease in humans. 2. Clinical syndromes The incidence of listeriosis varies between 0.1 and 11.3/ 1,000,000 in different countries [1]. Most reported cases present as life-threatening illness in one of three clinical syndromes: maternofetal listeriosis or neonatal listeriosis, blood stream infection, and meningoencephalitis. Listeriosis has an average case-fatality rate of 20e30% despite adequate antimicrobial treatment. In addition to these syndromes, listeriosis may present as a focal infection as a result of hematogenous spread. Focal infections most commonly involve the peritoneum, joints, the endocardium, or the eyes. The infectious dose in invasive listeriosis is not known but may be low in
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susceptible individuals. Elucidation of the epidemiology of listeriosis has been hampered by the often long incubation period of the disease, often exceeding 30 days. Besides the invasive forms, listeriosis may present as a febrile gastroenteritis and as cutaneous listeriosis. These presentations are self-limiting clinical conditions with non-specific symptoms and are therefore probably vastly underdiagnosed. Febrile gastroenteritis may affect persons with no known immunocompromising condition following ingestion of likely high numbers of organisms, after which the victim develops fever and diarrhea within 24 h; the illness usually resolves spontaneously. Cutaneous listeriosis is an eczematous skin infection caused by direct exposure of intact skin to L. monocytogenes, typically in a veterinarian exposed to a diseased animal often after a listerial abortion [3]. 3. Antimicrobial susceptibility of Listeria monocytogenes and treatment of listeriosis Isolates of L. monocytogenes are naturally susceptible to penicillins, aminoglycosides, trimethoprim, tetracycline, macrolides, and vancomycin. They show reduced susceptiblity or resistance to sulfomethoxazole, cephalosporins and old quinolones but are generally susceptible to fluoroquinolones [4]. Acquired antimicrobial resistance in clinical strains is rare [5] but has been found with a significant frequency in animal isolates [6]. This finding is a cause for concern and may indicate that resistance in clinical human isolates may emerge. Treatment of invasive listeriosis is supportive therapy accompanied by high doses of intravenous penicillin or ampicillin often in combination with an aminoglycoside. The drug of choice in patients with known allergy to penicillins is vancomycin/teicoplanin or trimethoprim/sulfamethoxazole. Cephalosporins should not be used for treatment of listeriosis. Clinical experience with fluoroquinolones is lacking. 4. Risk factors for listeriosis Invasive listeriosis occurs mainly in persons at the extremes of age, those with immunocompromising conditions, and those undergoing immunosuppressive therapy. However, the infection may also occur in people with no known predisposing factors [7]. In maternofetal or neonatal listeriosis occurring within the first week of life (‘‘early-onset neonatal listeriosis’’), the fetus is thought to acquire the infection in utero through transplacental migration of the organism from the bloodstream of the mother. The mother usually experiences non-specific flulike symptoms, whereas the fetus develops a systemic infection because its immune system is not sufficiently developed. This leads to fetal distress, death or premature birth of a severely ill infant. The risk of death due to listeriosis in an infant is inversely related to gestational age. Little is known about listeriosis as a cause of spontaneous abortion, though; it is probably not a common cause of this condition. If maternofetal listeriosis is diagnosed early, antimicrobial treatment of the mother will cure the disease in the infant [8]. However, this
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rarely occurs because the diagnosis is often missed because symptoms in the mother are non-specific. Listeriosis occurring in an infant more than a week after birth is called late-onset neonatal listeriosis. The route of transmission in this condition may be transplacental, as in early-onset disease, orally acquired during passage through a contaminated birth canal, or through contact with an external source. Certain conditions have been identified as risk factors for invasive listeriosis outside the neonatal period: old age, malignancies, diabetes mellitus, alcoholism, liver, renal and autoimmune diseases and other immunosuppressing conditions or treatments. The major defense of the body against listeriosis is cell-mediated immunity and therefore people with T-cell dysfunction seem to be particularly prone to contracting the disease. Of malignancies, hematological diseases carry the highest risk of listeriosis. Persons with immunological suppression due to HIV infection are considered to be at increased risk for listeriosis. However, because the number of severely immunosuppressed HIV infected individuals has decreased after the introduction of anti-retroviral therapies, the contribution of AIDS as a predisposing factor for listeriosis is expected to decrease in the future. Organ transplant patients and patients with end-stage renal disease are also at elevated risk for listeriosis. A larger proportion of patients with bloodstream infections have underlying risk factors as opposed to patients presenting with meningoencephalitis [9]. Until recently it was not known if the same risk factors that predispose people to listeriosis, also increase their risk of dying from the disease. A recent study conducted in Denmark [10] indicated that the factors that increased the risk of contracting listeriosis were also associated with death from the disease in patients below 70 years of age. Above this age, the presence of the predisposing factor did not add to the risk of death, possibly due to declining T-cell function with increasing age; the youngest patient who died without predisposing conditions, was 64 years old. Thus, the case-fatality rate was dependent on the presence of predisposing factors in the patients; it was 3% in the younger group with no predisposing factors, 24% in young patients with predisposing factors, and 20% in patients older than 70 years. The only single predisposing condition that was statistically associated with increased mortality by a multivariate analysis in that study was non-hematological malignancy. However, the number of patients with each predisposing condition was low, rendering the statistical power of the study findings low. This study did not show any differences in the case-fatality rate between patients suffering from blood stream infection vs meningoencephalitis. Differences in virulence between strains may also influence infection and clinical outcome. Serotypes 1/2a, 1/2b, and 1/2c are the types most frequently isolated from food or the food production environment. However, more than 95% of infections in humans are caused by the three serotypes 1/2a, 1/2b, and 4b. A majority of listeriosis outbreaks are caused by strains of serotype 4b. The rate of isolation of serotype 4b is higher among patients suffering from meningoencephalitis than in patients suffering from blood stream infection, indicating that strains of serotype 4b may be more virulent than
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other serotypes. The Danish study [10] also showed a higher mortality rate in patients infected with strains of serogroup 4; 26% of patients infected with L. monocytogenes serogroup 4 died compared with 16% of patients infected with serogroup 1/2, once again indicating that serogroup 4 strains may be more virulent. The molecular basis of the increased virulence of serogroup 4 is virtually unknown at present. Internalin, a protein associated with internalization of Listeria into the cells, is expressed in full-length in all serogroup 4 strains, whereas this is not always the case with serogroup 1/2 strains [11]. However, the prevalence of deficient (truncated) internalin in the serogroup 1/2 strains is too rare to allow us to attribute the increased virulence of serogroup 4 strains to the presence of complete internalin. Sequencing and proteomic studies of strains of different serotypes may shed light on this question. More patients with predisposing conditions seem to suffer from blood stream infection due to L. monocytogenes than meningoencephalitis. The reason for this finding may not be related to the virulence of the infecting organism or the susceptibility of the host. A likely explanation is that patients with predisposing conditions are in closer contact with the health system and, therefore, are more likely to have drawn blood for culture in case of fever than a person with no predisposing condition. In contrast, meningoencephalitis is such a severe disease that it will not pass unrecognized even in patients without predisposing conditions. 5. Outbreaks of listeriosis Although only a small proportion of listeriosis cases are due to common source outbreaks, public health officials place a high priority on investigating listeriosis outbreaks for the following reasons:
1. Listeriosis is a serious disease and has a very high mortality rate. Also, it affects persons with impaired immune systems. 2. From a public health standpoint, it is extremely important to identify the contaminated food vehicle and remove it from food distribution channels as rapidly as possible. This will reduce additional morbidity and mortality. 3. Outbreak investigations offer unique opportunities to identify the source of contamination of implicated foods, to learn more about the transmission of L. monocytogenes to humans, and to identify measures to prevent future cases. The investigation of the listeriosis outbreak in the Maritime Provinces of Canada (Table 1) provided conclusive evidence for the first time of foodborne transmission of L. monocytogenes. The outbreak was detected because of the unusually high number of perinatal listeriosis at a Nova Scotia hospital over a 3month period. Caseecontrol studies implicated coleslaw as the most likely vehicle of infection. Microbiological confirmation of coleslaw as the source of the infections was obtained by isolation of the same strain of L. monocytogenes from coleslaw obtained from a patient’s refrigerator, and from unopened packages of coleslaw from the manufacturer. Further investigation indicated that cabbage used to produce the coleslaw was probably contaminated by sheep manure and the L. monocytogenes had adequate opportunities to multiply during the storage of the cabbage over the winter months [2]. An outbreak of listeriosis in Massachusetts in 1983 raised serious questions about the efficacy of fluid milk pasteurization in inactivating L. monocytogenes. Caseecontrol studies and food intake history of cases revealed that case-patients were significantly more likely to have consumed whole or pasteurized milk purchased from a specific grocery store chain.
Table 1 International foodborne disease outbreaks of invasive listeriosis, 1980e2005 Year
Location
No. of cases
Perinatal cases
No. of deaths
Suspect/implicated vehicle
Serotype
1981 1983 1985 1983e1987 1987e1989 1989e1990 1992 1993 1998e1999 1999 1999e2000 1999e2000 2000
Nova Scotia, Canada Massachusetts, USA California, USA Switzerland United Kingdom Denmark France France Multiple states, USA Finland France France Multiple states, USA
41 49 142 122 366 26 279 38 108 25 10 32 30
34 7 94 65 ? 3 0 31 ? 0 3 9 8
18 14 48 34 ? 7 85 10 14 6 3 10 7
4b 4b 4b 4b 4bx 4b 4b 4b 4b 3a 4b 4b 1/2a
2000
North Carolina, USA
13
11
5
2002
Multiple states, USA
54
12
8
2002
Quebec, Canada
17
3
0
2003
Texas, USA
12
Coleslaw Pasteurized milk Mexican-style cheese Vacherin Mont d’Or cheese Pate´ Blue mold cheese Pork tongue in jelly Rillettes Hot dogs Butter Rillettes Pork tongue in aspic Delicatessen turkey ready-to-eat meats Home-made Mexican-style cheese Delicatessen turkey ready-to-eat meats Cheese made from raw milk Mexican-style cheese
?
?
4b 4b
4b
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The implication of pasteurized milk as the source of the outbreak was surprising. A review of the pasteurization records at the milk processing facility did not reveal any equipment defects or process deviations from the norm. However, cows at the farms that supplied milk to the processing facility were reported to have had Listeria infection at the time of the outbreak. This led to the hypothesis that the abnormally high pathogen load in the raw milk may have overwhelmed the pasteurization process or that localization of some L. monocytogenes within bovine cells may have protected them from heat inactivation. Subsequent research reaffirmed the effectiveness of pasteurization for fluid milk [12,13]. A large Mexican-style cheese outbreak in California in 1985 established L. monocytogenes as a high-priority pathogen for foodborne disease. Like the Canadian outbreak, this outbreak included a large proportion of perinatal infections, most of which were in Hispanic women. Caseecontrol studies established that the outbreak was associated with the consumption of a specific brand of soft, unripened Mexican-style cheese; this was confirmed by the isolation of L. monocytogenes of the same serotype and bacteriophage type from the implicated cheese [14]. The contamination was most likely caused by inadequate pasteurization of milk or by the mixing of raw milk with pasteurized milk for cheese making. A large outbreak in Switzerland, a 2000 outbreak in North Carolina, a 2002 outbreak in Canada, and a 2003 outbreak in Texas again highlight the risks posed by the use of raw milk in the manufacture of soft, unripened cheese. These outbreaks have caused public health officials to recommend that raw milk and dairy products prepared from raw milk should not be consumed by susceptible populations, particularly pregnant women. Contaminated ready-to-eat (RTE) meats are another major source of human listeriosis infections in outbreak settings. Outbreaks attributable to this food group include a 1987e 1999 pate´ outbreak in the United Kingdom, 1992,1993 and 1999e2000 outbreaks in France, and 1998e1999, 2000 and 2002 multistate outbreaks in the United States. RTE meats may be contaminated at low levels during the manufacturing process; the L. monocytogenes have ample opportunities to multiply to unsafe levels during refrigerated storage of the products during distribution and at the consumer’s home. Because these products are usually fully cooked during manufacture and are usually consumed without further heating or after just warming, they present high risks to the consumer, if they
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are contamined with L. monocytogenes at the processing facility. RTE meats have been the focus of several risk assessments and have been specifically targeted for Listeria control by food regulatory agencies and food processors. An unusual outbreak of listeriosis among patients at a tertiary care hospital in Finland [15] was caused by an uncommon serotype of L. monocyotgenes (serotype 3a). The outbreak strain had been previously isolated from a sample of butter produced at a Finnish dairy which supplied the hospital, and was isolated from butter samples collected from the hospital kitchen, indicating that the butter was a likely vehicle of infection. However, a caseecontrol study conducted to identify the source of infection did not implicate butter, probably because only seven of 25 case-patients were available for interviews. Nevertheless, investigators found that case-patients consumed four times as much butter as the control patients enrolled in the study. During the past 10 years, listeriosis outbreaks with febrile gastroenteritis as the predominant clinical manifestation have been reported from several countries (Table 2) [10,11,16e 21]. These outbreaks differed from invasive listeriosis outbreaks in several respects. They had shorter incubation times (18e27 h; Swedish outbreak: 1e15 days) and the symptoms included fever, diarrhea lasting up to 5 days, vomiting, arthralgia, headache and body pain. Most affected persons were healthy adults with no known immunocompromising conditions. Also, in outbreaks where quantitative cultures were done, exposure was to very high levels of the pathogen. Additional cases of invasive listeriosis in immunocompromised patients were identified by enhanced surveillance after a chocolate milk-associated febrile gastroenteritis outbreak in the United States [22]. Data from this outbreak investigation suggest that febrile gastroenteritis may occur in immunocompetent persons due to high levels of pathogen in foods rather than unique properties of outbreak strains. Epidemiologic investigations of invasive listeriosis outbreaks are particularly complex for two reasons: (1) the long incubation time (5e70 days) for invasive listeriosis makes it very difficult to obtain accurate food histories from case-patients, particularly from elderly patients; (2) because listeriosis primarily affects persons with immunocompromised status, the selection of appropriate controls for caseecontrol studies becomes problematic. Epidemiologists have attempted to address the first problem by promptly interviewing all cases of
Table 2 Gastrointestinal listeriosis outbreaks, 1993e2001 Year
Location
No. of cases
Implicated vehicle
Serotype
Pathogen load (CFU/g or ml)
1993 1994 1997 1998 2000 2001 2001 2001
Northern Italy Illinois, USA Northern Italy Finland New Zealand California, USA Sweden Japan
18 44 1566
Rice salad Chocolate milk Cold corn and tuna salad Cold-smoked fish Ready-to-eat meats Delicatessen turkey ready-to-eat meat Raw milk cheese Cheese
1/2b 1/2b 4b 1/2a 1/2 1/2a 1/2a 1/2b
>103 109 106 2 105 >2 105 >109 101e107 Not known
32 16 48 38
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listeriosis as soon they are notified about the case. They have addressed the second problem by selecting control patients for caseecontrol studies from among listeriosis patients who are diagnosed with the infection during the outbreak period but are infected with an unrelated strain. This approach has been found to be very effective in recent outbreak investigations [23e26]. Molecular subtyping plays a critical role in early recognition of listeriosis outbreaks and in their investigations. It is particularly useful for recognizing geographically diffuse clusters of cases if the subtyping is done promptly after clinical isolates are obtained using a standardized protocol, the subtype patterns are submitted without delay to a national database, and the national database is continually monitored for cluster detection [27]. This is presently done in the United States and France and has significantly increased outbreak recognition capabilities in both countries. In addition, thirteen European nations have the capacity to subtype L. monocyotgenes by pulsed-field gel electrophoresis, are performing PFGE subtyping of clinical isolates routinely or for ad hoc studies, are willing to use a standardized subtyping protocol, and are willing to contribute the subtype profiles to a European database [28]. 6. Risk assessment and prevention strategies Microbiological risk assessment provides an estimate of the probability of illness from a specific pathogen in a given population. It is a structured and objective process comprised of four steps: hazard identification, hazard characterization, exposure assessment, and risk characterization. Risk assessment, risk management and risk communication together constitute risk analysis. Risk analysis has a wide range of applications in food safety ranging from impacting national food safety policies (leading to the promulgation of new food regulations and/or enhanced enforcement of existing regulations) to institution of specific sanitation measures to achieve pathogen reduction at a certain points in the farm-to-table continuum [29]. In 2003, the US Food and Drug Administration, in collaboration with the Food Safety and Inspection Service of the US Department of Agriculture and the Centers for Disease Control and Prevention, released the results of a risk assessment to predict the potential relative risk of listeriosis from eating certain ready-to-eat foods among three age-based groups of people: perinatal (16 weeks after fertilization to 30 days after birth), elderly (60 years of age and older), and intermediate-age (general population, less than 60 years of age) [30]. This assessment evaluated foods within 23 categories considered to be principal potential sources of Listeria (Table 3). Deli meats were categorized in the ‘‘very high risk’’ category. From the exposure models and ‘‘what-if scenarios’’ used in the risk assessment, it was determined that the following five factors affected consumer exposure to L. monocytogenes at the time of food consumption: (1) amount and frequency of consumption of a food, (2) frequency and levels of L. monocytogenes in ready-to-eat food, (3) the likelihood of the growth of L. monocytogenes in a food during refrigerated storage, (4)
refrigerated storage temperature, and (5) duration of refrigerated storage of a food before consumption. The risk assessment model was used to estimate the likely impact of control strategies by changing one or two input parameters and measuring the change in the model outputs. For example, one ‘‘what-if’’ scenario determined that the predicted number of listeriosis cases would be reduced by 69% if all home refrigerators were consistently operating at or below 7.2 C. Another scenario determined that reducing the maximum storage time of deli meats from 28 to 14 days will reduce the median number of cases in the elderly population by 13.6%. Following an outbreak of listeriosis attributed to contaminated ‘‘rillettes’’ (a type of pate produced from pork that has a shelf-life of approximately 42 days, and is typically removed from the refrigerator and placed back multiple times at home), investigators determined that there was a significant difference in the number of times (6 vs. 4) the food product was moved between the refrigerator and the dining table between case households and control households [31]. Also, it was determined that an initial contamination level of 1 colony forming unit (CFU) per 100 g would render the product dangerous in 32 days whereas an initial contamination level of 10 CFU/g would render the product unsafe within 8 days. Salvat and Fravalo [31] examined the risk factors at the pig production and processing stages and concluded that live pigs frequently harbor L. monocyotgenes strains implicated in epidemic outbreaks and suggested that future prevention efforts should be focused on reducing the contamination on the farms and at the slaughterhouses. The Australia New Zealand Food Authority (ANZFA) conducted risk assessments of L. monocytogenes in cooked crustacean and cold-smoked salmon [32]. The ANZFA recommended a zero tolerance level for L. monocytogenes in cooked crustacean because there is potential for cooked crustacean to be contaminated with L. monocyotgenes, the pathogen proliferates rapidly in cooked crustacea, and because there is a distinct possibility of human illness if the product undergoes temperature abuse even for a short time. The risk assessment for cold-smoked salmon indicated that there is potential for the product to be contaminated with L. monocytogenes. Even though the growth of the pathogen in smoked salmon was only moderate, the health risk to susceptible populations was deemed high because the shelf-life of smoked salmon is long (4e6 weeks). However, because the coldsmoking process is not listericidal, the ANZFA decided not to amend the existing microbiological criteria for L. monocyotgenes in processed ready-to-eat finfish, which permit a level up to 100 CFU/g in one of five samples, with the L. monocytogenes ‘‘not detected’’ in the remaining four samples. At the international level, the FAO/WHO Listeria Risk Assessment Group undertook the task of determining how risk assessments previously conducted at national levels could be adapted or suitably expanded to address concerns related to L. monocyotgenes in RTE at the international level. Also, this group was asked by the 33rd session of the Codex Committee on Food Hygiene to consider three specific questions related to RTE foods in general [29]. Those questions and
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Table 3 Relative risk ranking and predicted median cases of listeriosis for the total United States population on a per serving and per annum basis Relative risk ranking
Predicted median cases of listeriosis for 23 food categories Per serving basisa Risk
1 2 3
High
4 5 6 7
Moderate
8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23
Low
Per annum basisb Food
Cases 8
Deli meats Frankfurters, not reheated Paˆte´ and meat spreads
7.7 10 6.5 108 3.2 108
Unpasteurized fluid milk Smoked seafood Cooked ready-to-eat crustaceans High fat and other dairy products Soft unripened cheese
7.1 109 6.2 109 5.1 109
Pasteurized fluid milk Fresh soft cheese Frankfurters, reheated Preserved fish Raw seafood
1.0 109 1.7 1010 6.3 1011 2.3 1011 2.0 1011
Fruits Dry/semi-dry fermented sausages Semi-soft cheese Soft ripened cheese Vegetables Deli-type salads Ice cream and other frozen dairy products Processed cheese Cultured milk products Hard cheese
1.9 1011 1.7 1011
Risk
Food
Cases
Very high High
Deli meats Pasteurized fluid milk High fat and other dairy products Frankfurters, not reheated Soft unripened cheese Paˆte´ and meat spreads
1598.7 90.8 56.4
Moderate
30.5 7.7 3.8
2.7 109
Unpasteurized fluid milk
3.1
1.8 109
Cooked ready-to-eat crustaceans Smoked seafood Fruits Frankfurters, reheated Vegetables Dry/semi-dry fermented sausages Fresh soft cheese Semi-soft cheese
2.8
6.5 1012 5.1 1012 2.8 1012 5.6 1013 4.9 1014 4.2 1014 3.2 1014 4.5 1015
Low
Soft ripened cheese Deli-type salads Raw seafood Preserved fish Ice cream and other frozen dairy products Processed cheese Cultured milk products Hard cheese
1.3 0.9 0.4 0.2 <0.1 <0.1 <0.1 <0.1 <0.1 <0.1 <0.1 <0.1 <0.1 <0.1 <0.1
Table reproduced from reference [26]. a Food categories were classified as high risk (>5 cases per billion servings), moderate risk (5 but 1 case per billion servings), and low risk (<1 case per billion servings). b Food categories were classified as very high risk (>100 cases per annum), high risk (>10e100 cases per annum), moderate risk (1e10 cases per annum), and low risk (<1 cases per annum).
the answers developed by the FAO/WHO Listeria Risk Assessment Group [30] are as follows: 1. Estimate the risk for consumers in different susceptible population groups relative to the general population. 2. The probability of becoming ill from ingesting L. monocytogenes is higher for susceptible populations (immunocompromised, elderly and perinatal) than the general population. The elderly (60þ years) were 2.6 times more susceptible while perinatals were 14 times more susceptible. 3. Estimate the risk for L. monocytogenes in foods that support the growth and foods that do not support growth under specific storage and shelf-life conditions. 4. The vast majority of listeriosis are caused by consumption of high numbers of L. monocytogenes. Eliminating higher levels of L. monocytogenes at consumption has a large impact on the number of predicted cases of illness. 5. Estimate the risk from L. monocytogenes in food when the number of organisms ranges from absence in 25 g to 1000 CFU/g, or does not exceed specified levels at the point of consumption.
6. The potential for multiplication of L. monocytogenes in RTE foods during refrigerated storage strongly influences risk. RTE foods that support the growth of L. monocytogenes present 100e1000-fold increased risk of listeriosis on a per-serving basis. 7. Control of Listeria monocytogenes in the food processing environment It is not realistic to expect that food processing establishments can be continuously maintained free of Listeria species. Despite best efforts, Listeria are likely to be reintroduced into food processing environments that, if neglected, will eventually lead to contamination of RTE foods. Tompkin [33] outlined a six-step Listeria control program for food processing environments. These are: (1) prevention of the establishment and growth of Listeria species in niches or other sites that can lead to contamination of RTE foods; (2) implementation of a sampling program to assess how well the control program is working; (3) rapid and effective response when the sampling program yields positive results for Listeria species;
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(4) verification by follow-up sampling to ensure that the source of contamination has been identified and corrected; (5) short-term assessment of the last 4e8 samplings to facilitate early detection of problems and trends; and (6) long-term assessment at appropriate intervals (quarterly, annually, etc.) to identify widely scattered contamination events and to measure overall progress towards continuous improvement. They emphasized that the design of the environmental sampling program and the response to positive findings by the sampling program determine the overall effectiveness of the Listeria control program in food processing environments. 8. Trends in the occurrence of invasive listeriosis The incidence of listeriosis has been declining in most industrialized countries during the past decade. The incidence of sporadic listeriosis declined by 40% between 1996e1998 and 2004 to 2.7 cases per million persons in the United States [34] and by 68% between 1987 and 1997 to 4.1 cases per million persons in France [35]. This is most likely due to the aggressive implementation of Listeria control measures by the food industry with introduction of HACCP principles to guide food production, and the implementation and enforcement of microbiological criteria for L. monocytogenes in food with a zero or low tolerance in most countries for ready-to-eat foods that support growth of the organism, e.g. deli meat, dairy products or smoked fish. Consumer education campaigns, especially those targeting the risk groups may also have contributed to the decline. Many countries have seen a shift in the L. monocytogenes serotypes causing human infections from predominantly serotype 4b to 1/2a and 1/2b and blood stream infection is now a more common clinical presentation than meningoencephalitis. Large outbreaks have become less frequent. The serotype shift may be related to the latter two observations; serotype 1/2a and 1/2b infections are more common in blood stream infections than in meningoencephalitis and the chance a blood stream infection will be detected has increased because the blood culturing systems have become more sensitive and the indications for drawing a blood culture have become broader the past 20 years; at the same time the large outbreaks which predominantly are caused by serogroup 4b strains have become rarer. Taken together this will lead to an increase in the number of diagnosed cases infected with serotype 1/2a and 1/2b and to a decrease in the number of infections caused by serotype 4b; i.e. a reversal of 1/2a and 1/2b: 4b ratio observed in cases of listeriosis. 9. Conclusions Our knowledge of Listeria monocytogenes and listeriosis has increased exponentially during the past 25 years. By applying this new information to food production and processing, it has been possible to reduce the incidence of listeriosis in the industrialized countries of the world. However, listeriosis cannot be entirely eliminated. Listeria monocytogenes occurs naturally in the environment and will inevitably contaminate the food that we eat from time to time. Education
of consumers, especially those who fall into the high risk groups, about high-risk foods and safe kitchen, will be necessary to keep morbidity and mortality due to listeriosis as low as possible. Continued refinement of practices in the farmto-fork continuum aimed at preventing Listeria from entering the food-chain will be the cornerstone of listeriosis prevention and control strategies.
References [1] Anonymous, Microbiological Risk Assessment Series, No. 5, Technical Report, WHO, Rome, 2004. [2] W.F. Schlech 3rd, P.M. Lavigne, R.A. Bortolussi, A.C. Allen, E.V. Haldane, A.J. Wort, A.W. Hightower, S.E. Johnson, S.H. King, E.S. Nicholls, C.V. Broome, Epidemic listeriosiseevidence for transmission by food, N. Engl. J. Med. 308 (1983) 203e206. [3] J. McLauchlin, J.C. Low, Primary cutaneous listeriosis in adults: an occupational disease of veterinarians and farmers, Vet. Rec. 135 (1994) 615e617. [4] R. Troxler, A. von Graevenitz, G. Funke, B. Wiedemann, I. Stock, Natural antibiotic susceptibility of Listeria species: L. grayi, L. innocua, L. ivanovii, L. monocytogenes, L. seeligeri and L. welshimeri strains, Clin. Microbiol. Infect. 6 (2000) 525e535. [5] J.M. Hansen, P. Gerner-Smidt, B. Bruun, Antibiotic susceptibility of Listeria monocytogenes in Denmark 1958-2001, APMIS 113 (2005) 31e36. [6] V. Srinivasan, H.M. Nam, L.T. Nguyen, B. Tamilselvam, S.E. Murinda, S.P. Oliver, Prevalence of antimicrobial resistance genes in Listeria monocytogenes isolated from dairy farms, Foodborne Pathog. Dis. 2 (2005) 201e211. [7] J. Rocourt, J. Bille, Foodborne listeriosis, World Health Stat. Q. 50 (1997) 67e73. [8] H.M. Silver, Listeriosis during pregnancy, Obstet. Gynecol. Surv. 53 (1998) 737e740. [9] J. McLauchlin, Human listeriosis in Britain, 1967e85, a summary of 722 cases. 2. Listeriosis in non-pregnant individuals, a changing pattern of infection and seasonal incidence, Epidemiol. Infect. 104 (1990) 191e201. [10] P. Gerner-Smidt, S. Ethelberg, P. Schiellerup, J.J. Christensen, J. Engberg, V. Fussing, A. Jensen, C. Jensen, A.M. Petersen, B.G. Bruun, Invasive listeriosis in Denmark 1994e2003: a review of 299 cases with special emphasis on risk factors for mortality, Clin. Microbiol. Infect. 11 (2005) 618e624. [11] C. Jacquet, M. Doumith, J.I. Gordon, P.M. Martin, P. Cossart, M. Lecuit, A molecular marker for evaluating the pathogenic potential of foodborne Listeria monocytogenes, J. Infect. Dis. 189 (2004) 2094e2100. [12] V.K. Bunning, R.G. Crawford, J.T. Tierney, J.T. Peeler, Thermotolerance of heat-shocked Listeria monocytogenes in milk exposed to high-temperature, short-time pasteurization, Appl. Environ. Microbiol. 58 (1992) 2096e2098. [13] J.M. Farber, G.W. Sanders, J.I. Speirs, J.Y. D’Aoust, D.B. Emmons, R. McKellar, Thermal resistance of Listeria monocytogenes in inoculated and naturally contaminated raw milk, Int. J. Food Microbiol. 7 (1988) 277e286. [14] M.J. Linnan, L. Mascola, X.D. Lou, V. Goulet, S. May, C. Salminen, D.W. Hird, M.L. Yonekura, P. Hayes, R. Weaver, et al., Epidemic listeriosis associated with Mexican-style cheese, N. Engl. J. Med. 319 (1988) 823e828. [15] O. Lyytikainen, T. Autio, R. Maijala, P. Ruutu, T. Honkanen-Buzalski, M. Miettinen, M. Hatakka, J. Mikkola, V.J. Anttila, T. Johansson, L. Rantala, T. Aalto, H. Korkeala, A. Siitonen, An outbreak of Listeria monocytogenes serotype 3a infections from butter in Finland, J. Infect. Dis. 181 (2000) 1838e1841. [16] P. Aureli, G.C. Fiorucci, D. Caroli, G. Marchiaro, O. Novara, L. Leone, S. Salmaso, An outbreak of febrile gastroenteritis associated with corn contaminated by Listeria monocytogenes, N. Engl. J. Med. 342 (2000) 1236e1241.
B. Swaminathan, P. Gerner-Smidt / Microbes and Infection 9 (2007) 1236e1243 [17] C.B. Dalton, C.C. Austin, J. Sobel, P.S. Hayes, W.F. Bibb, L.M. Graves, B. Swaminathan, M.E. Proctor, P.M. Griffin, An outbreak of gastroenteritis and fever due to Listeria monocytogenes in milk, N. Engl. J. Med. 336 (1997) 100e105. [18] M.L. Danielsson-Tham, E. Eriksson, S. Helmersson, M. Leffler, L. Ludtke, M. Steen, S. Sorgjerd, W. Tham, Causes behind a human cheese-borne outbreak of gastrointestinal listeriosis, Foodborne Pathog. Dis. 1 (2004) 153e159. [19] D.M. Frye, R. Zweig, J. Sturgeon, M. Tormey, M. LeCavalier, I. Lee, L. Lawani, L. Mascola, An outbreak of febrile gastroenteritis associated with delicatessen meat contaminated with Listeria monocytogenes, Clin. Infect. Dis. 35 (2002) 943e949. [20] S.I. Makino, K. Kawamoto, K. Takeshi, Y. Okada, M. Yamasaki, S. Yamamoto, S. Igimi, An outbreak of food-borne listeriosis due to cheese in Japan, during 2001, Int. J. Food Microbiol. 104 (2005) 189e196. [21] G. Salamina, E. Dalle Donne, A. Niccolini, G. Poda, D. Cesaroni, M. Bucci, R. Fini, M. Maldini, A. Schuchat, B. Swaminathan, W. Bibb, J. Rocourt, N. Binkin, S. Salmaso, A foodborne outbreak of gastroenteritis involving Listeria monocytogenes, Epidemiol. Infect. 117 (1996) 429e436. [22] M.E. Proctor, R. Brosch, J.W. Mellen, L.A. Garrett, C.W. Kaspar, J.B. Luchansky, Use of pulsed-field gel electrophoresis to link sporadic cases of invasive listeriosis with recalled chocolate milk, Appl. Environ. Microbiol. 61 (1995) 3177e3179. [23] H. de Valk, V. Vaillant, C. Jacquet, J. Rocourt, F. Le Querrec, F. Stainer, N. Quelquejeu, O. Pierre, V. Pierre, J.C. Desenclos, V. Goulet, Two consecutive nationwide outbreaks of listeriosis in France, October 1999e February 2000, Am. J. Epidemiol. 154 (2001) 944e950. [24] S.L. Gottlieb, E.C. Newbern, P.M. Griffin, L.M. Graves, R.M. Hoekstra, N.L. Baker, S.B. Hunter, K.G. Holt, F. Ramsey, M. Head, P. Levine, G. Johnson, D. Schoonmaker-Bopp, V. Reddy, L. Kornstein, M. Gerwel, J. Nsubuga, L. Edwards, S. Stonecipher, S. Hurd, D. Austin, M.A. Jefferson, S.D. Young, K. Hise, E.D. Chernak, J. Sobel, Multistate outbreak of listeriosis linked to turkey deli meat and subsequent changes in US regulatory policy, Clin. Infect. Dis. 42 (2006) 29e36. [25] P.S. Mead, E.F. Dunne, L. Graves, M. Wiedmann, M. Patrick, S. Hunter, E. Salehi, F. Mostashari, A. Craig, P. Mshar, T. Bannerman, B.D. Sauders, P. Hayes, W. Dewitt, P. Sparling, P. Griffin, D. Morse, L. Slutsker, B. Swaminathan, Nationwide outbreak of listeriosis due to contaminated meat, Epidemiol. Infect. (2005) 1e8. [26] S.J. Olsen, M. Patrick, S.B. Hunter, V. Reddy, L. Kornstein, W.R. MacKenzie, K. Lane, S. Bidol, G.A. Stoltman, D.M. Frye, I. Lee,
[27]
[28]
[29]
[30]
[31]
[32]
[33] [34]
[35]
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S. Hurd, T.F. Jones, T.N. LaPorte, W. Dewitt, L. Graves, M. Wiedmann, D.J. Schoonmaker-Bopp, A.J. Huang, C. Vincent, A. Bugenhagen, J. Corby, E.R. Carloni, M.E. Holcomb, R.F. Woron, S.M. Zansky, G. Dowdle, F. Smith, S. Ahrabi-Fard, A.R. Ong, N. Tucker, N.A. Hynes, P. Mead, Multistate outbreak of Listeria monocytogenes infection linked to delicatessen turkey meat, Clin. Infect. Dis. 40 (2005) 962e967. L.M. Graves, S.B. Hunter, A.R. Ong, D. Schoonmaker-Bopp, K. Hise, L. Kornstein, W.E. DeWitt, P.S. Hayes, E. Dunne, P. Mead, B. Swaminathan, Microbiological aspects of the investigation that traced the 1998 outbreak of listeriosis in the United States to contaminated hot dogs and establishment of molecular subtyping-based surveillance for Listeria monocytogenes in the PulseNet network, J. Clin. Microbiol. 43 (2005) 2350e2355. H. De Valk, C. Jacquet, V. Goulet, V. Vaillant, A. Perra, F. Simon, J.C. Desenclos, P. Martin, Surveillance of Listeria infections in Europe, Eur. Surveill. 10 (2005). J. Rocourt, P. BenEmbarek, H. Toyofuku, J. Schlundt, Quantitative risk assessment of Listeria monocytogenes in ready-to-eat foods: the FAO/ WHO approach, FEMS Immunol. Med. Microbiol. 35 (2003) 263e267. Anonymous, Interpretive summary: quantitative assessment of the relative risk to public health from foodborne Listeria monocytogenes among selected categories of ready-to-eat meats, Center for Food Safety and Applied Nutrition, Food and Drug Administration, US Department of Health and Human Services; Food Safety and Inspection Service, US Department of Agriculture, Washington, DC, 2003. G. Salvat, P. Fravalo, Risk assessment strategies for Europe: integrated safety strategy or final product control: example of Listeria monocytogenes in processed products from pork meat industry, Dtsch. Tierarztl. Wochenschr. 111 (2004) 331e334. Anonymous, Final Assessment Report: Proposal 239 e Listeria Risk Assessment & Risk Management Strategy, Food Standards Australia New Zealand, Canberra and Wellington, 2002. R.B. Tompkin, Control of Listeria monocytogenes in the food-processing environment, J. Food Prot. 65 (2002) 709e725. CDC, Preliminary FoodNet Data on the Incidence of Infection with Pathogens Transmitted Commonly Through Food e 10 Sites, United States, 2004, MMWR 54 (2005) 352e356. V. Goulet, H. de Valk, O. Pierre, F. Stainer, J. Rocourt, V. Vaillant, C. Jacquet, J.C. Desenclos, Effect of prevention measures on incidence of human listeriosis, France, 1987e1997, Emerg. Infect. Dis. 7 (2001) 983e989.
Forum
The epidemiology of human listeriosis* Bala Swaminathan*, Peter Gerner-Smidt Foodborne and Diarrheal Diseases Branch, Division of Bacterial and Mycotic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road, MS C03, Atlanta, GA 30333, USA Available online 7 May 2007
Abstract Listeriosis is a serious invasive disease that primarily afflicts pregnant women, neonates and immunocompromised adults. The causative organism, Listeria monocytogenes, is primarily transmitted to humans through contaminated foods. Outbreaks of listeriosis have been reported in North America, Europe and Japan. Soft cheeses made from raw milk and ready-to-eat meats are high risk foods for susceptible individuals. Efforts by food processors and food regulatory agencies to aggressively control L. monocytogenes in the high risk foods have resulted in significant decreases in the incidence of sporadic listeriosis. Ó 2007 Published by Elsevier Masson SAS. Keywords: Listeriosis; Listeria monocytogenes; Epidemiology
1. Introduction Listeria monocytogenes is a Gram-positive bacterial species that occurs ubiquitously in nature. First described in 1926 as the cause of an epizootic outbreak in guinea pigs and rabbits [1], it was not until it caused a large outbreak of invasive disease with a high case-fatality rate in the maritime provinces in Canada [2] that it was recognized as a serious public health problem. This outbreak for the first time demonstrated L. monocytogenes as a foodborne pathogen and it is now believed that most cases of human listeriosis are foodborne. Since this outbreak there has been a tremendous interest in elucidating the epidemiology of this organism in order to protect the consumer against listeriosis in the most cost-effective manner. The bacterium possesses properties that favor it as a foodborne pathogen: at variance with most other pathogens it is relatively resistant to acid and high salt concentrations; it grows at low temperature, down to freezing point, which mean it may grow in refrigerated foods. Before the development of Listeria selective media, this property was used for selective
*
Use of trade names is for identification only and does not imply endorsement by the Centers for Disease Control and Prevention or by the US Department of Health and Human Services. * Corresponding author. Tel.: þ1 404 639 3669; fax: þ1 404 639 3333. E-mail address: [email protected] (B. Swaminathan). 1286-4579/$ - see front matter Ó 2007 Published by Elsevier Masson SAS. doi:10.1016/j.micinf.2007.05.011
enrichment of the bacterium from complex matrices, with Listeria outnumbering the competing flora after incubation of the enrichment culture at refrigerator temperature for weeks or months. Additionally, L. monocytogenes readily produces biofilm that helps it to survive for prolonged periods in food production plants; an example of survival for more than 10 years in the same production environment has been described. Because of its ubiquitous nature, L. monocytogenes commonly contaminates raw produce and, through cross-contamination, other food items. Thus, all human beings are routinely exposed to L. monocyotgenes. Despite this, listeriosis is a relatively rare disease in humans. 2. Clinical syndromes The incidence of listeriosis varies between 0.1 and 11.3/ 1,000,000 in different countries [1]. Most reported cases present as life-threatening illness in one of three clinical syndromes: maternofetal listeriosis or neonatal listeriosis, blood stream infection, and meningoencephalitis. Listeriosis has an average case-fatality rate of 20e30% despite adequate antimicrobial treatment. In addition to these syndromes, listeriosis may present as a focal infection as a result of hematogenous spread. Focal infections most commonly involve the peritoneum, joints, the endocardium, or the eyes. The infectious dose in invasive listeriosis is not known but may be low in
B. Swaminathan, P. Gerner-Smidt / Microbes and Infection 9 (2007) 1236e1243
susceptible individuals. Elucidation of the epidemiology of listeriosis has been hampered by the often long incubation period of the disease, often exceeding 30 days. Besides the invasive forms, listeriosis may present as a febrile gastroenteritis and as cutaneous listeriosis. These presentations are self-limiting clinical conditions with non-specific symptoms and are therefore probably vastly underdiagnosed. Febrile gastroenteritis may affect persons with no known immunocompromising condition following ingestion of likely high numbers of organisms, after which the victim develops fever and diarrhea within 24 h; the illness usually resolves spontaneously. Cutaneous listeriosis is an eczematous skin infection caused by direct exposure of intact skin to L. monocytogenes, typically in a veterinarian exposed to a diseased animal often after a listerial abortion [3]. 3. Antimicrobial susceptibility of Listeria monocytogenes and treatment of listeriosis Isolates of L. monocytogenes are naturally susceptible to penicillins, aminoglycosides, trimethoprim, tetracycline, macrolides, and vancomycin. They show reduced susceptiblity or resistance to sulfomethoxazole, cephalosporins and old quinolones but are generally susceptible to fluoroquinolones [4]. Acquired antimicrobial resistance in clinical strains is rare [5] but has been found with a significant frequency in animal isolates [6]. This finding is a cause for concern and may indicate that resistance in clinical human isolates may emerge. Treatment of invasive listeriosis is supportive therapy accompanied by high doses of intravenous penicillin or ampicillin often in combination with an aminoglycoside. The drug of choice in patients with known allergy to penicillins is vancomycin/teicoplanin or trimethoprim/sulfamethoxazole. Cephalosporins should not be used for treatment of listeriosis. Clinical experience with fluoroquinolones is lacking. 4. Risk factors for listeriosis Invasive listeriosis occurs mainly in persons at the extremes of age, those with immunocompromising conditions, and those undergoing immunosuppressive therapy. However, the infection may also occur in people with no known predisposing factors [7]. In maternofetal or neonatal listeriosis occurring within the first week of life (‘‘early-onset neonatal listeriosis’’), the fetus is thought to acquire the infection in utero through transplacental migration of the organism from the bloodstream of the mother. The mother usually experiences non-specific flulike symptoms, whereas the fetus develops a systemic infection because its immune system is not sufficiently developed. This leads to fetal distress, death or premature birth of a severely ill infant. The risk of death due to listeriosis in an infant is inversely related to gestational age. Little is known about listeriosis as a cause of spontaneous abortion, though; it is probably not a common cause of this condition. If maternofetal listeriosis is diagnosed early, antimicrobial treatment of the mother will cure the disease in the infant [8]. However, this
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rarely occurs because the diagnosis is often missed because symptoms in the mother are non-specific. Listeriosis occurring in an infant more than a week after birth is called late-onset neonatal listeriosis. The route of transmission in this condition may be transplacental, as in early-onset disease, orally acquired during passage through a contaminated birth canal, or through contact with an external source. Certain conditions have been identified as risk factors for invasive listeriosis outside the neonatal period: old age, malignancies, diabetes mellitus, alcoholism, liver, renal and autoimmune diseases and other immunosuppressing conditions or treatments. The major defense of the body against listeriosis is cell-mediated immunity and therefore people with T-cell dysfunction seem to be particularly prone to contracting the disease. Of malignancies, hematological diseases carry the highest risk of listeriosis. Persons with immunological suppression due to HIV infection are considered to be at increased risk for listeriosis. However, because the number of severely immunosuppressed HIV infected individuals has decreased after the introduction of anti-retroviral therapies, the contribution of AIDS as a predisposing factor for listeriosis is expected to decrease in the future. Organ transplant patients and patients with end-stage renal disease are also at elevated risk for listeriosis. A larger proportion of patients with bloodstream infections have underlying risk factors as opposed to patients presenting with meningoencephalitis [9]. Until recently it was not known if the same risk factors that predispose people to listeriosis, also increase their risk of dying from the disease. A recent study conducted in Denmark [10] indicated that the factors that increased the risk of contracting listeriosis were also associated with death from the disease in patients below 70 years of age. Above this age, the presence of the predisposing factor did not add to the risk of death, possibly due to declining T-cell function with increasing age; the youngest patient who died without predisposing conditions, was 64 years old. Thus, the case-fatality rate was dependent on the presence of predisposing factors in the patients; it was 3% in the younger group with no predisposing factors, 24% in young patients with predisposing factors, and 20% in patients older than 70 years. The only single predisposing condition that was statistically associated with increased mortality by a multivariate analysis in that study was non-hematological malignancy. However, the number of patients with each predisposing condition was low, rendering the statistical power of the study findings low. This study did not show any differences in the case-fatality rate between patients suffering from blood stream infection vs meningoencephalitis. Differences in virulence between strains may also influence infection and clinical outcome. Serotypes 1/2a, 1/2b, and 1/2c are the types most frequently isolated from food or the food production environment. However, more than 95% of infections in humans are caused by the three serotypes 1/2a, 1/2b, and 4b. A majority of listeriosis outbreaks are caused by strains of serotype 4b. The rate of isolation of serotype 4b is higher among patients suffering from meningoencephalitis than in patients suffering from blood stream infection, indicating that strains of serotype 4b may be more virulent than
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other serotypes. The Danish study [10] also showed a higher mortality rate in patients infected with strains of serogroup 4; 26% of patients infected with L. monocytogenes serogroup 4 died compared with 16% of patients infected with serogroup 1/2, once again indicating that serogroup 4 strains may be more virulent. The molecular basis of the increased virulence of serogroup 4 is virtually unknown at present. Internalin, a protein associated with internalization of Listeria into the cells, is expressed in full-length in all serogroup 4 strains, whereas this is not always the case with serogroup 1/2 strains [11]. However, the prevalence of deficient (truncated) internalin in the serogroup 1/2 strains is too rare to allow us to attribute the increased virulence of serogroup 4 strains to the presence of complete internalin. Sequencing and proteomic studies of strains of different serotypes may shed light on this question. More patients with predisposing conditions seem to suffer from blood stream infection due to L. monocytogenes than meningoencephalitis. The reason for this finding may not be related to the virulence of the infecting organism or the susceptibility of the host. A likely explanation is that patients with predisposing conditions are in closer contact with the health system and, therefore, are more likely to have drawn blood for culture in case of fever than a person with no predisposing condition. In contrast, meningoencephalitis is such a severe disease that it will not pass unrecognized even in patients without predisposing conditions. 5. Outbreaks of listeriosis Although only a small proportion of listeriosis cases are due to common source outbreaks, public health officials place a high priority on investigating listeriosis outbreaks for the following reasons:
1. Listeriosis is a serious disease and has a very high mortality rate. Also, it affects persons with impaired immune systems. 2. From a public health standpoint, it is extremely important to identify the contaminated food vehicle and remove it from food distribution channels as rapidly as possible. This will reduce additional morbidity and mortality. 3. Outbreak investigations offer unique opportunities to identify the source of contamination of implicated foods, to learn more about the transmission of L. monocytogenes to humans, and to identify measures to prevent future cases. The investigation of the listeriosis outbreak in the Maritime Provinces of Canada (Table 1) provided conclusive evidence for the first time of foodborne transmission of L. monocytogenes. The outbreak was detected because of the unusually high number of perinatal listeriosis at a Nova Scotia hospital over a 3month period. Caseecontrol studies implicated coleslaw as the most likely vehicle of infection. Microbiological confirmation of coleslaw as the source of the infections was obtained by isolation of the same strain of L. monocytogenes from coleslaw obtained from a patient’s refrigerator, and from unopened packages of coleslaw from the manufacturer. Further investigation indicated that cabbage used to produce the coleslaw was probably contaminated by sheep manure and the L. monocytogenes had adequate opportunities to multiply during the storage of the cabbage over the winter months [2]. An outbreak of listeriosis in Massachusetts in 1983 raised serious questions about the efficacy of fluid milk pasteurization in inactivating L. monocytogenes. Caseecontrol studies and food intake history of cases revealed that case-patients were significantly more likely to have consumed whole or pasteurized milk purchased from a specific grocery store chain.
Table 1 International foodborne disease outbreaks of invasive listeriosis, 1980e2005 Year
Location
No. of cases
Perinatal cases
No. of deaths
Suspect/implicated vehicle
Serotype
1981 1983 1985 1983e1987 1987e1989 1989e1990 1992 1993 1998e1999 1999 1999e2000 1999e2000 2000
Nova Scotia, Canada Massachusetts, USA California, USA Switzerland United Kingdom Denmark France France Multiple states, USA Finland France France Multiple states, USA
41 49 142 122 366 26 279 38 108 25 10 32 30
34 7 94 65 ? 3 0 31 ? 0 3 9 8
18 14 48 34 ? 7 85 10 14 6 3 10 7
4b 4b 4b 4b 4bx 4b 4b 4b 4b 3a 4b 4b 1/2a
2000
North Carolina, USA
13
11
5
2002
Multiple states, USA
54
12
8
2002
Quebec, Canada
17
3
0
2003
Texas, USA
12
Coleslaw Pasteurized milk Mexican-style cheese Vacherin Mont d’Or cheese Pate´ Blue mold cheese Pork tongue in jelly Rillettes Hot dogs Butter Rillettes Pork tongue in aspic Delicatessen turkey ready-to-eat meats Home-made Mexican-style cheese Delicatessen turkey ready-to-eat meats Cheese made from raw milk Mexican-style cheese
?
?
4b 4b
4b
B. Swaminathan, P. Gerner-Smidt / Microbes and Infection 9 (2007) 1236e1243
The implication of pasteurized milk as the source of the outbreak was surprising. A review of the pasteurization records at the milk processing facility did not reveal any equipment defects or process deviations from the norm. However, cows at the farms that supplied milk to the processing facility were reported to have had Listeria infection at the time of the outbreak. This led to the hypothesis that the abnormally high pathogen load in the raw milk may have overwhelmed the pasteurization process or that localization of some L. monocytogenes within bovine cells may have protected them from heat inactivation. Subsequent research reaffirmed the effectiveness of pasteurization for fluid milk [12,13]. A large Mexican-style cheese outbreak in California in 1985 established L. monocytogenes as a high-priority pathogen for foodborne disease. Like the Canadian outbreak, this outbreak included a large proportion of perinatal infections, most of which were in Hispanic women. Caseecontrol studies established that the outbreak was associated with the consumption of a specific brand of soft, unripened Mexican-style cheese; this was confirmed by the isolation of L. monocytogenes of the same serotype and bacteriophage type from the implicated cheese [14]. The contamination was most likely caused by inadequate pasteurization of milk or by the mixing of raw milk with pasteurized milk for cheese making. A large outbreak in Switzerland, a 2000 outbreak in North Carolina, a 2002 outbreak in Canada, and a 2003 outbreak in Texas again highlight the risks posed by the use of raw milk in the manufacture of soft, unripened cheese. These outbreaks have caused public health officials to recommend that raw milk and dairy products prepared from raw milk should not be consumed by susceptible populations, particularly pregnant women. Contaminated ready-to-eat (RTE) meats are another major source of human listeriosis infections in outbreak settings. Outbreaks attributable to this food group include a 1987e 1999 pate´ outbreak in the United Kingdom, 1992,1993 and 1999e2000 outbreaks in France, and 1998e1999, 2000 and 2002 multistate outbreaks in the United States. RTE meats may be contaminated at low levels during the manufacturing process; the L. monocytogenes have ample opportunities to multiply to unsafe levels during refrigerated storage of the products during distribution and at the consumer’s home. Because these products are usually fully cooked during manufacture and are usually consumed without further heating or after just warming, they present high risks to the consumer, if they
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are contamined with L. monocytogenes at the processing facility. RTE meats have been the focus of several risk assessments and have been specifically targeted for Listeria control by food regulatory agencies and food processors. An unusual outbreak of listeriosis among patients at a tertiary care hospital in Finland [15] was caused by an uncommon serotype of L. monocyotgenes (serotype 3a). The outbreak strain had been previously isolated from a sample of butter produced at a Finnish dairy which supplied the hospital, and was isolated from butter samples collected from the hospital kitchen, indicating that the butter was a likely vehicle of infection. However, a caseecontrol study conducted to identify the source of infection did not implicate butter, probably because only seven of 25 case-patients were available for interviews. Nevertheless, investigators found that case-patients consumed four times as much butter as the control patients enrolled in the study. During the past 10 years, listeriosis outbreaks with febrile gastroenteritis as the predominant clinical manifestation have been reported from several countries (Table 2) [10,11,16e 21]. These outbreaks differed from invasive listeriosis outbreaks in several respects. They had shorter incubation times (18e27 h; Swedish outbreak: 1e15 days) and the symptoms included fever, diarrhea lasting up to 5 days, vomiting, arthralgia, headache and body pain. Most affected persons were healthy adults with no known immunocompromising conditions. Also, in outbreaks where quantitative cultures were done, exposure was to very high levels of the pathogen. Additional cases of invasive listeriosis in immunocompromised patients were identified by enhanced surveillance after a chocolate milk-associated febrile gastroenteritis outbreak in the United States [22]. Data from this outbreak investigation suggest that febrile gastroenteritis may occur in immunocompetent persons due to high levels of pathogen in foods rather than unique properties of outbreak strains. Epidemiologic investigations of invasive listeriosis outbreaks are particularly complex for two reasons: (1) the long incubation time (5e70 days) for invasive listeriosis makes it very difficult to obtain accurate food histories from case-patients, particularly from elderly patients; (2) because listeriosis primarily affects persons with immunocompromised status, the selection of appropriate controls for caseecontrol studies becomes problematic. Epidemiologists have attempted to address the first problem by promptly interviewing all cases of
Table 2 Gastrointestinal listeriosis outbreaks, 1993e2001 Year
Location
No. of cases
Implicated vehicle
Serotype
Pathogen load (CFU/g or ml)
1993 1994 1997 1998 2000 2001 2001 2001
Northern Italy Illinois, USA Northern Italy Finland New Zealand California, USA Sweden Japan
18 44 1566
Rice salad Chocolate milk Cold corn and tuna salad Cold-smoked fish Ready-to-eat meats Delicatessen turkey ready-to-eat meat Raw milk cheese Cheese
1/2b 1/2b 4b 1/2a 1/2 1/2a 1/2a 1/2b
>103 109 106 2 105 >2 105 >109 101e107 Not known
32 16 48 38
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listeriosis as soon they are notified about the case. They have addressed the second problem by selecting control patients for caseecontrol studies from among listeriosis patients who are diagnosed with the infection during the outbreak period but are infected with an unrelated strain. This approach has been found to be very effective in recent outbreak investigations [23e26]. Molecular subtyping plays a critical role in early recognition of listeriosis outbreaks and in their investigations. It is particularly useful for recognizing geographically diffuse clusters of cases if the subtyping is done promptly after clinical isolates are obtained using a standardized protocol, the subtype patterns are submitted without delay to a national database, and the national database is continually monitored for cluster detection [27]. This is presently done in the United States and France and has significantly increased outbreak recognition capabilities in both countries. In addition, thirteen European nations have the capacity to subtype L. monocyotgenes by pulsed-field gel electrophoresis, are performing PFGE subtyping of clinical isolates routinely or for ad hoc studies, are willing to use a standardized subtyping protocol, and are willing to contribute the subtype profiles to a European database [28]. 6. Risk assessment and prevention strategies Microbiological risk assessment provides an estimate of the probability of illness from a specific pathogen in a given population. It is a structured and objective process comprised of four steps: hazard identification, hazard characterization, exposure assessment, and risk characterization. Risk assessment, risk management and risk communication together constitute risk analysis. Risk analysis has a wide range of applications in food safety ranging from impacting national food safety policies (leading to the promulgation of new food regulations and/or enhanced enforcement of existing regulations) to institution of specific sanitation measures to achieve pathogen reduction at a certain points in the farm-to-table continuum [29]. In 2003, the US Food and Drug Administration, in collaboration with the Food Safety and Inspection Service of the US Department of Agriculture and the Centers for Disease Control and Prevention, released the results of a risk assessment to predict the potential relative risk of listeriosis from eating certain ready-to-eat foods among three age-based groups of people: perinatal (16 weeks after fertilization to 30 days after birth), elderly (60 years of age and older), and intermediate-age (general population, less than 60 years of age) [30]. This assessment evaluated foods within 23 categories considered to be principal potential sources of Listeria (Table 3). Deli meats were categorized in the ‘‘very high risk’’ category. From the exposure models and ‘‘what-if scenarios’’ used in the risk assessment, it was determined that the following five factors affected consumer exposure to L. monocytogenes at the time of food consumption: (1) amount and frequency of consumption of a food, (2) frequency and levels of L. monocytogenes in ready-to-eat food, (3) the likelihood of the growth of L. monocytogenes in a food during refrigerated storage, (4)
refrigerated storage temperature, and (5) duration of refrigerated storage of a food before consumption. The risk assessment model was used to estimate the likely impact of control strategies by changing one or two input parameters and measuring the change in the model outputs. For example, one ‘‘what-if’’ scenario determined that the predicted number of listeriosis cases would be reduced by 69% if all home refrigerators were consistently operating at or below 7.2 C. Another scenario determined that reducing the maximum storage time of deli meats from 28 to 14 days will reduce the median number of cases in the elderly population by 13.6%. Following an outbreak of listeriosis attributed to contaminated ‘‘rillettes’’ (a type of pate produced from pork that has a shelf-life of approximately 42 days, and is typically removed from the refrigerator and placed back multiple times at home), investigators determined that there was a significant difference in the number of times (6 vs. 4) the food product was moved between the refrigerator and the dining table between case households and control households [31]. Also, it was determined that an initial contamination level of 1 colony forming unit (CFU) per 100 g would render the product dangerous in 32 days whereas an initial contamination level of 10 CFU/g would render the product unsafe within 8 days. Salvat and Fravalo [31] examined the risk factors at the pig production and processing stages and concluded that live pigs frequently harbor L. monocyotgenes strains implicated in epidemic outbreaks and suggested that future prevention efforts should be focused on reducing the contamination on the farms and at the slaughterhouses. The Australia New Zealand Food Authority (ANZFA) conducted risk assessments of L. monocytogenes in cooked crustacean and cold-smoked salmon [32]. The ANZFA recommended a zero tolerance level for L. monocytogenes in cooked crustacean because there is potential for cooked crustacean to be contaminated with L. monocyotgenes, the pathogen proliferates rapidly in cooked crustacea, and because there is a distinct possibility of human illness if the product undergoes temperature abuse even for a short time. The risk assessment for cold-smoked salmon indicated that there is potential for the product to be contaminated with L. monocytogenes. Even though the growth of the pathogen in smoked salmon was only moderate, the health risk to susceptible populations was deemed high because the shelf-life of smoked salmon is long (4e6 weeks). However, because the coldsmoking process is not listericidal, the ANZFA decided not to amend the existing microbiological criteria for L. monocyotgenes in processed ready-to-eat finfish, which permit a level up to 100 CFU/g in one of five samples, with the L. monocytogenes ‘‘not detected’’ in the remaining four samples. At the international level, the FAO/WHO Listeria Risk Assessment Group undertook the task of determining how risk assessments previously conducted at national levels could be adapted or suitably expanded to address concerns related to L. monocyotgenes in RTE at the international level. Also, this group was asked by the 33rd session of the Codex Committee on Food Hygiene to consider three specific questions related to RTE foods in general [29]. Those questions and
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Table 3 Relative risk ranking and predicted median cases of listeriosis for the total United States population on a per serving and per annum basis Relative risk ranking
Predicted median cases of listeriosis for 23 food categories Per serving basisa Risk
1 2 3
High
4 5 6 7
Moderate
8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23
Low
Per annum basisb Food
Cases 8
Deli meats Frankfurters, not reheated Paˆte´ and meat spreads
7.7 10 6.5 108 3.2 108
Unpasteurized fluid milk Smoked seafood Cooked ready-to-eat crustaceans High fat and other dairy products Soft unripened cheese
7.1 109 6.2 109 5.1 109
Pasteurized fluid milk Fresh soft cheese Frankfurters, reheated Preserved fish Raw seafood
1.0 109 1.7 1010 6.3 1011 2.3 1011 2.0 1011
Fruits Dry/semi-dry fermented sausages Semi-soft cheese Soft ripened cheese Vegetables Deli-type salads Ice cream and other frozen dairy products Processed cheese Cultured milk products Hard cheese
1.9 1011 1.7 1011
Risk
Food
Cases
Very high High
Deli meats Pasteurized fluid milk High fat and other dairy products Frankfurters, not reheated Soft unripened cheese Paˆte´ and meat spreads
1598.7 90.8 56.4
Moderate
30.5 7.7 3.8
2.7 109
Unpasteurized fluid milk
3.1
1.8 109
Cooked ready-to-eat crustaceans Smoked seafood Fruits Frankfurters, reheated Vegetables Dry/semi-dry fermented sausages Fresh soft cheese Semi-soft cheese
2.8
6.5 1012 5.1 1012 2.8 1012 5.6 1013 4.9 1014 4.2 1014 3.2 1014 4.5 1015
Low
Soft ripened cheese Deli-type salads Raw seafood Preserved fish Ice cream and other frozen dairy products Processed cheese Cultured milk products Hard cheese
1.3 0.9 0.4 0.2 <0.1 <0.1 <0.1 <0.1 <0.1 <0.1 <0.1 <0.1 <0.1 <0.1 <0.1
Table reproduced from reference [26]. a Food categories were classified as high risk (>5 cases per billion servings), moderate risk (5 but 1 case per billion servings), and low risk (<1 case per billion servings). b Food categories were classified as very high risk (>100 cases per annum), high risk (>10e100 cases per annum), moderate risk (1e10 cases per annum), and low risk (<1 cases per annum).
the answers developed by the FAO/WHO Listeria Risk Assessment Group [30] are as follows: 1. Estimate the risk for consumers in different susceptible population groups relative to the general population. 2. The probability of becoming ill from ingesting L. monocytogenes is higher for susceptible populations (immunocompromised, elderly and perinatal) than the general population. The elderly (60þ years) were 2.6 times more susceptible while perinatals were 14 times more susceptible. 3. Estimate the risk for L. monocytogenes in foods that support the growth and foods that do not support growth under specific storage and shelf-life conditions. 4. The vast majority of listeriosis are caused by consumption of high numbers of L. monocytogenes. Eliminating higher levels of L. monocytogenes at consumption has a large impact on the number of predicted cases of illness. 5. Estimate the risk from L. monocytogenes in food when the number of organisms ranges from absence in 25 g to 1000 CFU/g, or does not exceed specified levels at the point of consumption.
6. The potential for multiplication of L. monocytogenes in RTE foods during refrigerated storage strongly influences risk. RTE foods that support the growth of L. monocytogenes present 100e1000-fold increased risk of listeriosis on a per-serving basis. 7. Control of Listeria monocytogenes in the food processing environment It is not realistic to expect that food processing establishments can be continuously maintained free of Listeria species. Despite best efforts, Listeria are likely to be reintroduced into food processing environments that, if neglected, will eventually lead to contamination of RTE foods. Tompkin [33] outlined a six-step Listeria control program for food processing environments. These are: (1) prevention of the establishment and growth of Listeria species in niches or other sites that can lead to contamination of RTE foods; (2) implementation of a sampling program to assess how well the control program is working; (3) rapid and effective response when the sampling program yields positive results for Listeria species;
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(4) verification by follow-up sampling to ensure that the source of contamination has been identified and corrected; (5) short-term assessment of the last 4e8 samplings to facilitate early detection of problems and trends; and (6) long-term assessment at appropriate intervals (quarterly, annually, etc.) to identify widely scattered contamination events and to measure overall progress towards continuous improvement. They emphasized that the design of the environmental sampling program and the response to positive findings by the sampling program determine the overall effectiveness of the Listeria control program in food processing environments. 8. Trends in the occurrence of invasive listeriosis The incidence of listeriosis has been declining in most industrialized countries during the past decade. The incidence of sporadic listeriosis declined by 40% between 1996e1998 and 2004 to 2.7 cases per million persons in the United States [34] and by 68% between 1987 and 1997 to 4.1 cases per million persons in France [35]. This is most likely due to the aggressive implementation of Listeria control measures by the food industry with introduction of HACCP principles to guide food production, and the implementation and enforcement of microbiological criteria for L. monocytogenes in food with a zero or low tolerance in most countries for ready-to-eat foods that support growth of the organism, e.g. deli meat, dairy products or smoked fish. Consumer education campaigns, especially those targeting the risk groups may also have contributed to the decline. Many countries have seen a shift in the L. monocytogenes serotypes causing human infections from predominantly serotype 4b to 1/2a and 1/2b and blood stream infection is now a more common clinical presentation than meningoencephalitis. Large outbreaks have become less frequent. The serotype shift may be related to the latter two observations; serotype 1/2a and 1/2b infections are more common in blood stream infections than in meningoencephalitis and the chance a blood stream infection will be detected has increased because the blood culturing systems have become more sensitive and the indications for drawing a blood culture have become broader the past 20 years; at the same time the large outbreaks which predominantly are caused by serogroup 4b strains have become rarer. Taken together this will lead to an increase in the number of diagnosed cases infected with serotype 1/2a and 1/2b and to a decrease in the number of infections caused by serotype 4b; i.e. a reversal of 1/2a and 1/2b: 4b ratio observed in cases of listeriosis. 9. Conclusions Our knowledge of Listeria monocytogenes and listeriosis has increased exponentially during the past 25 years. By applying this new information to food production and processing, it has been possible to reduce the incidence of listeriosis in the industrialized countries of the world. However, listeriosis cannot be entirely eliminated. Listeria monocytogenes occurs naturally in the environment and will inevitably contaminate the food that we eat from time to time. Education
of consumers, especially those who fall into the high risk groups, about high-risk foods and safe kitchen, will be necessary to keep morbidity and mortality due to listeriosis as low as possible. Continued refinement of practices in the farmto-fork continuum aimed at preventing Listeria from entering the food-chain will be the cornerstone of listeriosis prevention and control strategies.
References [1] Anonymous, Microbiological Risk Assessment Series, No. 5, Technical Report, WHO, Rome, 2004. [2] W.F. Schlech 3rd, P.M. Lavigne, R.A. Bortolussi, A.C. Allen, E.V. Haldane, A.J. Wort, A.W. Hightower, S.E. Johnson, S.H. King, E.S. Nicholls, C.V. Broome, Epidemic listeriosiseevidence for transmission by food, N. Engl. J. Med. 308 (1983) 203e206. [3] J. McLauchlin, J.C. Low, Primary cutaneous listeriosis in adults: an occupational disease of veterinarians and farmers, Vet. Rec. 135 (1994) 615e617. [4] R. Troxler, A. von Graevenitz, G. Funke, B. Wiedemann, I. Stock, Natural antibiotic susceptibility of Listeria species: L. grayi, L. innocua, L. ivanovii, L. monocytogenes, L. seeligeri and L. welshimeri strains, Clin. Microbiol. Infect. 6 (2000) 525e535. [5] J.M. Hansen, P. Gerner-Smidt, B. Bruun, Antibiotic susceptibility of Listeria monocytogenes in Denmark 1958-2001, APMIS 113 (2005) 31e36. [6] V. Srinivasan, H.M. Nam, L.T. Nguyen, B. Tamilselvam, S.E. Murinda, S.P. Oliver, Prevalence of antimicrobial resistance genes in Listeria monocytogenes isolated from dairy farms, Foodborne Pathog. Dis. 2 (2005) 201e211. [7] J. Rocourt, J. Bille, Foodborne listeriosis, World Health Stat. Q. 50 (1997) 67e73. [8] H.M. Silver, Listeriosis during pregnancy, Obstet. Gynecol. Surv. 53 (1998) 737e740. [9] J. McLauchlin, Human listeriosis in Britain, 1967e85, a summary of 722 cases. 2. Listeriosis in non-pregnant individuals, a changing pattern of infection and seasonal incidence, Epidemiol. Infect. 104 (1990) 191e201. [10] P. Gerner-Smidt, S. Ethelberg, P. Schiellerup, J.J. Christensen, J. Engberg, V. Fussing, A. Jensen, C. Jensen, A.M. Petersen, B.G. Bruun, Invasive listeriosis in Denmark 1994e2003: a review of 299 cases with special emphasis on risk factors for mortality, Clin. Microbiol. Infect. 11 (2005) 618e624. [11] C. Jacquet, M. Doumith, J.I. Gordon, P.M. Martin, P. Cossart, M. Lecuit, A molecular marker for evaluating the pathogenic potential of foodborne Listeria monocytogenes, J. Infect. Dis. 189 (2004) 2094e2100. [12] V.K. Bunning, R.G. Crawford, J.T. Tierney, J.T. Peeler, Thermotolerance of heat-shocked Listeria monocytogenes in milk exposed to high-temperature, short-time pasteurization, Appl. Environ. Microbiol. 58 (1992) 2096e2098. [13] J.M. Farber, G.W. Sanders, J.I. Speirs, J.Y. D’Aoust, D.B. Emmons, R. McKellar, Thermal resistance of Listeria monocytogenes in inoculated and naturally contaminated raw milk, Int. J. Food Microbiol. 7 (1988) 277e286. [14] M.J. Linnan, L. Mascola, X.D. Lou, V. Goulet, S. May, C. Salminen, D.W. Hird, M.L. Yonekura, P. Hayes, R. Weaver, et al., Epidemic listeriosis associated with Mexican-style cheese, N. Engl. J. Med. 319 (1988) 823e828. [15] O. Lyytikainen, T. Autio, R. Maijala, P. Ruutu, T. Honkanen-Buzalski, M. Miettinen, M. Hatakka, J. Mikkola, V.J. Anttila, T. Johansson, L. Rantala, T. Aalto, H. Korkeala, A. Siitonen, An outbreak of Listeria monocytogenes serotype 3a infections from butter in Finland, J. Infect. Dis. 181 (2000) 1838e1841. [16] P. Aureli, G.C. Fiorucci, D. Caroli, G. Marchiaro, O. Novara, L. Leone, S. Salmaso, An outbreak of febrile gastroenteritis associated with corn contaminated by Listeria monocytogenes, N. Engl. J. Med. 342 (2000) 1236e1241.
B. Swaminathan, P. Gerner-Smidt / Microbes and Infection 9 (2007) 1236e1243 [17] C.B. Dalton, C.C. Austin, J. Sobel, P.S. Hayes, W.F. Bibb, L.M. Graves, B. Swaminathan, M.E. Proctor, P.M. Griffin, An outbreak of gastroenteritis and fever due to Listeria monocytogenes in milk, N. Engl. J. Med. 336 (1997) 100e105. [18] M.L. Danielsson-Tham, E. Eriksson, S. Helmersson, M. Leffler, L. Ludtke, M. Steen, S. Sorgjerd, W. Tham, Causes behind a human cheese-borne outbreak of gastrointestinal listeriosis, Foodborne Pathog. Dis. 1 (2004) 153e159. [19] D.M. Frye, R. Zweig, J. Sturgeon, M. Tormey, M. LeCavalier, I. Lee, L. Lawani, L. Mascola, An outbreak of febrile gastroenteritis associated with delicatessen meat contaminated with Listeria monocytogenes, Clin. Infect. Dis. 35 (2002) 943e949. [20] S.I. Makino, K. Kawamoto, K. Takeshi, Y. Okada, M. Yamasaki, S. Yamamoto, S. Igimi, An outbreak of food-borne listeriosis due to cheese in Japan, during 2001, Int. J. Food Microbiol. 104 (2005) 189e196. [21] G. Salamina, E. Dalle Donne, A. Niccolini, G. Poda, D. Cesaroni, M. Bucci, R. Fini, M. Maldini, A. Schuchat, B. Swaminathan, W. Bibb, J. Rocourt, N. Binkin, S. Salmaso, A foodborne outbreak of gastroenteritis involving Listeria monocytogenes, Epidemiol. Infect. 117 (1996) 429e436. [22] M.E. Proctor, R. Brosch, J.W. Mellen, L.A. Garrett, C.W. Kaspar, J.B. Luchansky, Use of pulsed-field gel electrophoresis to link sporadic cases of invasive listeriosis with recalled chocolate milk, Appl. Environ. Microbiol. 61 (1995) 3177e3179. [23] H. de Valk, V. Vaillant, C. Jacquet, J. Rocourt, F. Le Querrec, F. Stainer, N. Quelquejeu, O. Pierre, V. Pierre, J.C. Desenclos, V. Goulet, Two consecutive nationwide outbreaks of listeriosis in France, October 1999e February 2000, Am. J. Epidemiol. 154 (2001) 944e950. [24] S.L. Gottlieb, E.C. Newbern, P.M. Griffin, L.M. Graves, R.M. Hoekstra, N.L. Baker, S.B. Hunter, K.G. Holt, F. Ramsey, M. Head, P. Levine, G. Johnson, D. Schoonmaker-Bopp, V. Reddy, L. Kornstein, M. Gerwel, J. Nsubuga, L. Edwards, S. Stonecipher, S. Hurd, D. Austin, M.A. Jefferson, S.D. Young, K. Hise, E.D. Chernak, J. Sobel, Multistate outbreak of listeriosis linked to turkey deli meat and subsequent changes in US regulatory policy, Clin. Infect. Dis. 42 (2006) 29e36. [25] P.S. Mead, E.F. Dunne, L. Graves, M. Wiedmann, M. Patrick, S. Hunter, E. Salehi, F. Mostashari, A. Craig, P. Mshar, T. Bannerman, B.D. Sauders, P. Hayes, W. Dewitt, P. Sparling, P. Griffin, D. Morse, L. Slutsker, B. Swaminathan, Nationwide outbreak of listeriosis due to contaminated meat, Epidemiol. Infect. (2005) 1e8. [26] S.J. Olsen, M. Patrick, S.B. Hunter, V. Reddy, L. Kornstein, W.R. MacKenzie, K. Lane, S. Bidol, G.A. Stoltman, D.M. Frye, I. Lee,
[27]
[28]
[29]
[30]
[31]
[32]
[33] [34]
[35]
1243
S. Hurd, T.F. Jones, T.N. LaPorte, W. Dewitt, L. Graves, M. Wiedmann, D.J. Schoonmaker-Bopp, A.J. Huang, C. Vincent, A. Bugenhagen, J. Corby, E.R. Carloni, M.E. Holcomb, R.F. Woron, S.M. Zansky, G. Dowdle, F. Smith, S. Ahrabi-Fard, A.R. Ong, N. Tucker, N.A. Hynes, P. Mead, Multistate outbreak of Listeria monocytogenes infection linked to delicatessen turkey meat, Clin. Infect. Dis. 40 (2005) 962e967. L.M. Graves, S.B. Hunter, A.R. Ong, D. Schoonmaker-Bopp, K. Hise, L. Kornstein, W.E. DeWitt, P.S. Hayes, E. Dunne, P. Mead, B. Swaminathan, Microbiological aspects of the investigation that traced the 1998 outbreak of listeriosis in the United States to contaminated hot dogs and establishment of molecular subtyping-based surveillance for Listeria monocytogenes in the PulseNet network, J. Clin. Microbiol. 43 (2005) 2350e2355. H. De Valk, C. Jacquet, V. Goulet, V. Vaillant, A. Perra, F. Simon, J.C. Desenclos, P. Martin, Surveillance of Listeria infections in Europe, Eur. Surveill. 10 (2005). J. Rocourt, P. BenEmbarek, H. Toyofuku, J. Schlundt, Quantitative risk assessment of Listeria monocytogenes in ready-to-eat foods: the FAO/ WHO approach, FEMS Immunol. Med. Microbiol. 35 (2003) 263e267. Anonymous, Interpretive summary: quantitative assessment of the relative risk to public health from foodborne Listeria monocytogenes among selected categories of ready-to-eat meats, Center for Food Safety and Applied Nutrition, Food and Drug Administration, US Department of Health and Human Services; Food Safety and Inspection Service, US Department of Agriculture, Washington, DC, 2003. G. Salvat, P. Fravalo, Risk assessment strategies for Europe: integrated safety strategy or final product control: example of Listeria monocytogenes in processed products from pork meat industry, Dtsch. Tierarztl. Wochenschr. 111 (2004) 331e334. Anonymous, Final Assessment Report: Proposal 239 e Listeria Risk Assessment & Risk Management Strategy, Food Standards Australia New Zealand, Canberra and Wellington, 2002. R.B. Tompkin, Control of Listeria monocytogenes in the food-processing environment, J. Food Prot. 65 (2002) 709e725. CDC, Preliminary FoodNet Data on the Incidence of Infection with Pathogens Transmitted Commonly Through Food e 10 Sites, United States, 2004, MMWR 54 (2005) 352e356. V. Goulet, H. de Valk, O. Pierre, F. Stainer, J. Rocourt, V. Vaillant, C. Jacquet, J.C. Desenclos, Effect of prevention measures on incidence of human listeriosis, France, 1987e1997, Emerg. Infect. Dis. 7 (2001) 983e989.