Clostridioides difficile (C. diff) infection (CDI) is a pathogen of both humans and animals, and to control it will require an integrated approach that encompasses human health care, veterinary health care, environmental regulation, and public policy. That is the conclusion of a group led by Su-Chen Lim, MD, and Tom Riley, MD, of Edith Cowan University in Australia, who published a review in Clinical Microbiology and Infection.
CDI was generally considered a nuisance infection until the early 21st century, when a hypervirulent fluoroquinolone-resistant strain emerged in North America. The strain is now documented In the United States, Canada, and most countries in Europe.
Another new feature of CDI is increased evidence of community transmission, which was previously rare. This is defined as cases where the patient experienced symptom onset outside the hospital, and had no history of hospitalization in the previous 12 weeks or symptom onset within 48 hours of hospital admission. Community-associated CDI now accounts for 41% of U.S. cases, nearly 30% of Australian cases, and about 14% in Europe, according to recent studies.
Several features of CDI suggest a need for an integrated management plan. The preferred habitat of C. diff is the gastrointestinal track of mammals, and likely colonizes all mammalian neonates. Over time, colonization by other microbes likely crowd it out and prevent overgrowth. But widespread use of antimicrobials in animal production can lead to the creation of an environment resembling that of the neonate, allowing C. diff to expand. That has led to food animals becoming a major C. diff reservoir, and whole-genome studies showed that strains found in humans, food, animals, and the environment are closely related and sometimes genetically indistinguishable, suggesting transmission between humans and animals that may be attributable to contaminated food and environments.
The authors suggest that C. diff infection control should be guided by the One Health initiative, which seeks cooperation between physicians, osteopathic physicians, veterinarians, dentists, nurses, and other scientific and environmental disciplines. The goal is to enhance surveillance and interdisciplinary communication, as well as integrated policies. The authors note that C. diff is often thought of by physicians as primarily a hospital problem, who may be unaware of the increased prevalence of community-acquired disease. It is also a significant problem in agriculture, since as many as 50% of piglets succumb to the disease. Other studies have recently shown that asymptomatic carriers of toxigenic strains are likely to transmit the bacteria to C. diff-negative patients. Asymptomatic carriers cluster with symptomatic patients. In one Cleveland hospital, more than 25% of hospital-associated CDI cases were found to have been colonized prior to admission, suggesting that these were not true hospital-associated cases.
C. diff has been isolated from a wide range of sources, including food animals, meat, seafood, vegetables, household environments, and natural environments like rivers, lakes, and soil. About 20% of calves and 70% of piglets are colonized with C. diff. It has a high prevalence in meat products in the United States, but lower in the Europe, possibly because of different slaughtering practices.
The authors suggest that zoonotic C. diff spread is unlikely to be confined to any geographic region or population, and that widespread C. diff contamination is occurring through food or the environment. This could be occurring because spores can withstand cooking temperatures and disseminate through the air, and even through manure from food animals made into compost or fertilizer.
Veterinary efforts mimicking hospital measures have reduced animal CDI, but there are no rapid diagnostic tests for CDI in animals, making it challenging to control its spread in this context.
The authors call for enhanced antimicrobial stewardship in both human and animal settings, including banning of antimicrobial agents as growth promoters. This has been done in the United States and Europe, but not in Brazil, China, Canada, India, and Australia. They also call for research on inactivation of C. diff spores during waste treatment.
Even better, the authors suggest that vaccines should be developed and employed in both animals and humans. No such vaccine exists in animals, but Pfizer has one for humans in a phase 3 clinical trial, but it does not prevent colonization. Others are in development.
The epidemiology of CDI is an ongoing challenge, with emerging new strains and changing social and environmental conditions. “However, it is with the collaborative efforts of industry partners, policymakers, veterinarians, clinicians, and researchers that CDI needs to be approached, a perfect example of One Health. Opening an interdisciplinary dialogue to address CDI and One Health issues has to be the focus of future studies,” the authors concluded.
SOURCE: SC Lim et al. Clinical Microbiology and Infection. 2020;26:85-863.