Clostridium

the most common food-borne diseases worldwide resulting from the contamination food. It is one of the most common causes of reported food-borne diseases in the United States.

Although several Staphylococcal enterotoxins (SEs) have been identified, SEA, a highly heat-stable SE, is the most common cause of SFD worldwide. Outbreak investigations have found that improper food handling practices in the retail industry account for the majority of SFD outbreaks. However, several studies have documented prevalence of S. aureus in many food products including raw retail meat indicating that consumers are at potential risk of S. aureus colonization and subsequent infection. Presence of pathogens in food products imposes potential hazard for consumers and causes grave economic loss and loss in human productivity via food-borne disease. Symptoms of SFD include nausea, vomiting, and abdominal cramps with or without diarrhea. Preventive measures include safe food handling and processing practice, maintaining cold chain, adequate cleaning and disinfection of equipment, prevention of cross-contamination in home and kitchen, and prevention of contamination from farm to fork. This paper provides a brief overview of SFD, contributing factors, risk that it imposes to the consumers, current research gaps, and preventive measures.

Clostridium difficile was first described as part of the normal microbiota in stool samples from healthy infants in 1935 (59) and is still detected in significant numbers of healthy asymptomatic infants (143). Later, it was identified as a pathogen associated with pseudomembranous colitis and occasionally with wound and lung infections. (12;96;153;153) Now it has become the most common cause of diarrhea in hospitals and long term care facilities causing billions of dollars in excess costs. (43) C. difficile contributes to the death of an estimated 14,000 people annually in the U.S. and over 90% of the fatalities are >65 years of age. (105) The elderly and those being treated with antibiotics to control other infections are most susceptible to C. difficile. Broad spectrum antibiotics destroy much of the normal intestinal microbiota allowing some resistant bacteria (such as C. difficile), that are normally not very competitive in this environment, to thrive. Although most cases of C. difficile infection (CDI) occur in patients in health care facilities, there has been a recent increase in community-acquired infections. C. difficile spores have been detected in meat, seafood, and some vegetables indicating a potential for foodborne transmission. C. botulinum and C. perfringens have been food safety concerns for decades because they produce potent toxins and their spores survive desiccation, many thermal treatments, and other preservation methods. Other clostridial species are known spoilage organisms. As yet, there has been no definitive proof that humans acquire C. difficile from contaminated food. However, since C. difficile is present in livestock and its spores survive ordinary cooking temperatures and some food processing conditions, foodborne transmission should be considered a possibility.

Over the last decade worldwide, Clostridium difficile infection

Clostridium difficile is a spore-forming gram-positive bacillus, and the leading cause of antibiotic-associated with diarrhea and colitis in developing countries. Although, the epidemiology of C. difficile infection has changed in the last decade. C. difficile infection, once thought to be an easy to treat bacterial infection, has evolved into an epidemic that is associated with a high rate of mortality, causing disease in patients thought to be low-risk.

and it is now increasingly recognized as a cause of diarrhea in the community. Classically considered a hospital-acquired infection, it has now emerged in populations previously considered to be low-risk and lacking the traditional risk factors for C. difficile infection, such as increased age, hospitalization, and antibiotic exposure. Recent studies have demonstrated great genetic diversity for C. difficile, pointing toward diverse sources and a fluid genome. Environmental sources like food, water, and animals may play an important role in these infections, apart from the role symptomatic patients and asymptomatic carriers play in spore dispersal. Prospective strain typing using highly discriminatory techniques is a possible way to explore the suspected diverse sources of C. difficile infection in the community. Patients with community-acquired C. difficile infection do not necessarily have a good outcome and clinicians should be aware of factors that predict worse outcomes in order to prevent them. This article summarizes the emerging epidemiology, risk factors, and outcomes for community-acquired C. difficile infection.

1. Definition of Problem – Use this portion of the paper to develop a good case for the problem that you interest. Talk about who is affected, why and how. Talk about demographics or people impacted here. You need to convince people that a problem exists, so this is your chance.

Potential routes of infection Epidemiology and transmission of C. difficile, particularly for community-acquired infections, are not completely understood. C. difficile is transmitted basically by the fecal-oral route but numerous exposure scenarios are possible. (121) High concentrations of spores (104 to 107 spores/g.) are present in feces of people and animals with active CDI. Prior to treatment about 90% of samples from the skin of hospitalized patients with CDI and of environmental samples in their rooms tested positive for C. difficile. Treatment caused resolution of diarrhea in an average of 4.2 days. Yet some patients and their environments still contained spores 6 weeks after treatment. (151) Person to Person Contact C. difficile is commonly present on the skin of patients with CDI, with highest counts generally present on the abdomen and lowest counts on the chest. Spores were readily transferred to moist gloved hands touching the skin of patients. It is believed that the hands of healthcare workers are an important means of transporting nosocomial pathogens throughout hospitals and other health facilities. (56) However, a study of the transmission of C. difficile in hospital wards at a large U.S. hospital indicated that transmission from patients with CDI was not sufficient to sustain transmission to other residents of the ward, Rather, admission of new colonized patients was an important factor in sustaining transmission. (95) Asymptomatic carriers may be an important source of C. difficile in the community and in long term care facilities. More than half of 68 asymptomatic residents at one facility were found to be carriers and C. difficile was present on their skin and in their environment. Spores on the skin were easily transferred to the hands of others suggesting that personnel attending these residents can spread C. difficile to other residents and areas of the facility. (132) Persons working in environments where they are routinely exposed to C. difficile, such as nurses, day care workers, some farm workers, and some persons working in veterinary clinics, may transport spores on their clothing from the workplace into their homes and the community. (121) Infants at day nurseries are often colonized with C. difficile and sometime secrete spores for several months. (143) Some data from Canada indicated that direct transmission of C. difficile from CDI cases to family members was not very common. (126)

Incidence of asymptomatic carriage of C. difficile in the healthy, general population has been estimated at 3%. However, some populations have a higher rate of carriage. A survey of 100 residents of a home for the elderly (median age 83) found that 10% were asymptomatic carriers of C. difficile. (145) A survey of 1234 Japanese adults with no history of antibiotic use during the previous 4 weeks found that 7.6% were asymptomatic carriers of C. difficile. (83) After treatment and resolution of symptoms, many CDI cases continue to shed C. difficile spores for as long as 4 weeks. (151) These spores are very resistant to sanitizers and environmental stresses and asymptomatic carriers may be sources of hospital- and community-acquired infections. Early outbreaks of C. difficile associated diarrhea (CDAD) or C. difficile infection (CDI) occurred in hospitals and epidemiological studies implicated the long-term use of antibiotics in the development of this disease. C. difficile is now the most common cause of diarrhea in hospitals and long term care facilities, particularly afflicting those being treated with antibiotics, such as cephalosporins and fluoroquinolines, to control other infections. Antibiotic treatment can destroy much of the normal intestinal flora allowing some resistant bacteria that are normally not very competitive (such as some strains of C. difficile) to thrive. Data from a 2010 survey of 89 German hospitals revealed that the incidence of nosocomial C. difficile infection was twice that of nosocomial MRSA infection. (113) Recurrent CDI occurs frequently, generally affecting more than a third of primary cases. An examination of the strains involved in the recurrent infections of 82 persons found that in 51 people, CDI symptoms occurring after an apparent cure were caused by the same C. difficile strain, indicating a relapse. In the other patients, a different C. difficile strain was detected indicating that a new infection occurred. Infection with 027 was a significant risk for relapse. (102) Several papers from a 2012 symposium discussed different aspects of the problem of recurrent C. difficile infections. (47) ME Doyle, Food Research Institute November 2012 UW–Madison, www.fri.wisc.edu/ Funded in part by the American Meat Institute Foundation 5 In the past 8 years, there has also been an increasing number of cases of C. difficile infection occurring outside of hospitals, among younger, healthy persons with no recent history of antibiotic use. (144;50)

Epidemiology of C. difficile Incidence of infection worldwide More than 250,000 hospitalizations each year in the U.S. are estimated to be associated with C. difficile infection and the economic burden of this illness is close to or may even exceed $1 billion annually. (43;106) A high incidence of CDI in hospitals significantly increases costs due to longer hospitalization, rehospitalization, more laboratory tests, and more medications. In uncomplicated cases, this may entail an extra $5000 per patient. But for special populations, for example patients being treated in intensive care units for other illnesses, the increased cost may be as much as $90,000 in 2008 dollars. (53) The economic burden of CDI is not limited to hospitals. Kaiser Permanente Colorado and NorthWest tracked CDI cases for 3 years and reported that more than half were identified in outpatients, with resulting costs to clinics and to patients who must stay home from work. (93) During the past 15 years the incidence of CDI in acute care hospitals in the U.S. has increased from 30-40/100,000 to >84/100,000. Data reported by CDC indicate that mortality from CDI has increased steadily from 793 deaths in 1999 to 7,476 deaths in 2008, dropping slightly to 7,284 in 2010. Approximately 91% of these deaths occurred in people aged 65 and older. (115) The increasing severity of illness correlates with the emergence of hypervirulent strains (ribotype O27/NAP1/toxinotype III and ribotype O78 toxinotype V) detected first in the U.S. and Canada in the early 2000s (87;114), then in Europe in 2005, and in Asia, Central America, and Australia in 2008-2010. (31) Similar recent increases in CDI have also been reported in Canada and Europe. Estimated burden of CDI in Europe is about 5 episodes per 10,000 days of hospital stay. However, this disease is believed to be significantly underreported because clinicians often fail to order tests for C. difficile in cases of unexplained diarrhea or else laboratories may use diagnostic tests with low sensitivity. Some CDI cases are missed because symptoms develop after the patient has been discharged from the hospital. Estimates for annual costs for managing CDI in Europe are about €3000 million. (24) CDI has become a problem in hospitals and communities in other countries and issues related to CDI in Latin America (10) and in Asia (46) were recently reviewed. Hypervirulent strains produce many more spores and higher levels of toxins than less virulent strains. Infectious dose of C. difficile required to cause illness depends on the virulence characteristics of a strain and the susceptibility of the host. There are no data for humans on infectious dose but an experiment with mice demonstrated that exposure to

2. Solution Options – Discuss some potential solutions that you think may be useful in addressing the problem. If you are citing solutions from other source, make sure to attribute the information to those sources.

Prevention of foodborne intoxication or infection

Although some preliminary data indicates that C. difficile can grow on media containing

meat or fish juice and on ground beef (159), this bacterium, like other clostridia, is an anaerobe

and does not grow in the presence of oxygen. It is not clear whether there are foods that will

support growth and toxin production by C. difficile or whether the critical issue is simply the

number of spores deposited on foods at the point of contamination. It appears that the structures

of toxins A and B are partially unfolded at 40-45°C (although they tended to be more stable at

higher pH values). (147) This suggests that the activity of toxins (if they were present in foods)

would be destroyed by cooking. However, the stability of the toxins in the presence of various

food constituents has not been determined. If spores are present in meat or other foods, they

would not be destroyed by ordinary cooking to recommended temperatures. (138)

Particularly for foods to be served to vulnerable populations in hospitals, nursing homes,

and elsewhere, efforts should be made to prevent contamination throughout the food production,

processing and preparation chain. Procedures used to reduce contamination with other intestinal

pathogens, for example E. coli and Salmonella, during slaughter and processing of livestock will

ME Doyle, Food Research Institute November 2012

UW–Madison, www.fri.wisc.edu/ Funded in part by the American Meat Institute Foundation

14

aid in diminishing C. difficile on carcasses and pieces of meat although spores will survive heat

and some cleaning/disinfection steps that would inactivate vegetative pathogens. Workers in

food processing and preparation have been implicated in outbreaks of foodborne disease. They

may shed bacteria and viruses, even when asymptomatic and several weeks after they have

recovered from an illness. Improved hygiene precautions, consistently practiced by persons in

food preparation and processing would significantly improve safety of foods. (167)

Data gaps and research needed

Further information and research is needed to determine whether C. difficile in food

presents a significant threat to human health.

• The few studies that have reported concentrations of spores in foods indicate that

contamination levels are very low. More data is needed on spore levels in different foods.

• There is not yet any good data on the possible growth and toxin production of C. difficile in

different foods. Although the presence of C. difficile in many foods may not be a risk for

illness, there may be certain foods that are more commonly or heavily contaminated with C.

difficile or environmental conditions that support growth of C. difficile and toxin production as

there are for C. botulinum and C. perfringens.

• C. difficile spores are known to survive ordinary cooking temperatures but further information

is needed on the ability of these spores to survive other processing conditions and

antimicrobials that may be added to foods.

• Nor is there enough information on the stability of toxins A and B at different temperatures or

pH values in foods.

• More rigorous genotyping methods are needed to determine whether C. difficile strains present

in animals, food, or environmental samples are the same as those isolated from human CDI

cases.

• The infectious dose of C. difficile in healthy persons or in those whose normal microbiota has

been depleted by antimicrobial use or those with other comorbid conditions is unknown.

Although we know that chlorine-based disinfectants can kill C. difficile spores, hospitals

and other healthcare facilities continue to experience problems with CDI. More research may be

needed on other effective disinfectants. Hospitals and other institutions with continuing

contamination problems may need to devise better organized systems for cleaning and

disinfection. This may involve: more rapid identification of contaminated areas, prevention of

contamination of instruments, minimizing production of aerosols containing C. difficile spores,

and educating and encouraging personnel to adhere to strict infection control procedures. These

strategies will also be important for food processors if C. difficile is determined to be a

foodborne pathogen.

Summary and Perspective

During the past 10-15 years, the frequency and severity of CDI in humans has increased.

While it is still true that the majority of infections occur in hospitals and other healthcare

facilities, in people over 65 years old, in those taking certain antibiotics such as fluoroquinolines

and in persons with other serious health issues, an increasing number of younger, healthy and

non-hospitalized persons have recently developed CDI. The emergence of hypervirulent strains,

ME Doyle, Food Research Institute November 2012

UW–Madison, www.fri.wisc.edu/ Funded in part by the American Meat Institute Foundation

15

ageing populations, newer wide-spectrum antibiotics, and increased exposure to C. difficile

outside of healthcare facilities may all have played a role in this changing epidemiology.

The normal habitat of C. difficile is the gastrointestinal tract of humans and other animals

(including livestock and companion animals). As such, large numbers of spores are present in

feces of infected people and animals as well as of asymptomatic carriers. Therefore, infection of

new hosts occurs by some version of the fecal-oral route. Although C. difficile has been detected

in many domestic animals, in water and soil samples and in some foods, there is as yet no direct

evidence for the transmission of this pathogen from the environment, foods, or animals to

humans.

There are many unanswered questions about the epidemiology of this pathogen and it

would be wise to monitor ongoing research on this organism to determine whether it poses a risk

as a foodborne pathog

3. Conclusions – Pick what you think is the best way to address the problem, given the solution options. Explain why you think that it is the best solution and what some of the benefits will be. Give the reader an idea as to what to expect 1, 5 10 years down the road. You do not have to be exact, but using these benchmarks is good as a way to convince people to recognize the problem and how it can be addressed.